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  • October 22, 2014
  • 04:26 AM
  • 67 views

Autism, parental concerns and socioeconomic status

by Paul Whiteley in Questioning Answers

I'd like to think that there are some rather important messages to be taken from the paper by Xiang Sun and colleagues [1] on level of parental concern, socioeconomic status (SES) and risk of autism. Not only did the authors conclude that: "a higher SES was not associated with the risk of having ASC [autism spectrum conditions]" they also found that: "No child met ASC criteria where parents expressed no concerns".Do you prefer "fashion victim" or "ensembly challenged"?SES - including variables such as family income, parental educational attainment(s) and parental occupation(s) - has been something of a talking point in autism research down the years and the rather mixed messages which have come out of the research literature on SES and offspring autism risk (see here). The growing appreciation that children of those positioned in a higher SES bracket don't seem to be at any significantly greater risk of autism is something rather important as per other evidence, for example, noted by Fujiwara [2]. Whether this means previous contrary findings were in error or that there has been some shift in the factors linked to the onset of contemporary autism is unknown at this time.Some of my first thoughts on the Sun SES findings were in relation to all the discussions about offspring autism potentially being associated with certain types of parental occupational choices [3]. Indeed, considering that the Sun study was both carried out in and originated from Cambridge (UK) and included Prof. Simon Baron-Cohen on the authorship team, it is coincidental that the findings could be construed as counter to such occupational links with autism (assuming that Physicists, Engineers and Mathematicians would be described as higher SES jobs).Of course I'm not saying the research on any relationship between offspring autism and parental occupation choice is all bunk; the paper from Windham and colleagues [4] and other evidence is too strong to negate (including that of occupational exposures potentially being involved). Merely that there may be much more to see than just a spectrum of 'talent' genes overlapping with autism risk genes [5] when it comes to receipt of a diagnosis on the very wide autism spectrum. Oh, and assuming you believe talent is all in the genes...The other finding from Sun et al discussing parental concern and potential diagnosis of autism in offspring also carries quite a bit of potential importance. Regular readers of this blog might already have picked up my respect for parents and carers as active agents both in terms of picking up the signs and symptoms of autism in their loved ones (see here) and also detecting and reporting other important comorbidity (see here). I see the Sun findings - "No child met ASC criteria where parents expressed no concerns" - as corroborating parents and caregivers as doing what they do best: knowing their own child. I might also suggest that the discussions on increasing autism rates solely being down to better awareness and greater diagnostic vigilance are not seemingly backed up by the Sun findings if we assume parental concerns represent the starting point of the diagnostic journey into autism.Some music to close. Gershon Kingsley and Popcorn.----------[1] Sun X. et al. Parental concerns, socioeconomic status, and the risk of autism spectrum conditions in a population-based study. Res Dev Disabil. 2014 Sep 25;35(12):3678-3688.[2] Fujiwara T. Socioeconomic status and the risk of suspected autism spectrum disorders among 18-month-old toddlers in Japan: a population-based study. J Autism Dev Disord. 2014 Jun;44(6):1323-31.[3] Baron-Cohen S. Does Autism Occur More Often in Families of Physicists, Engineers, and Mathematicians? Autism. 1998; 2: 296-301.[4] Windham GC. et al. Autism spectrum disorders in relation to parental occupation in technical fields. Autism Res. 2009 Aug;2(4):183-91.[5] Baron-Cohen S. Autism and the technical mind: children of scientists and engineers may inherit genes that not only confer intellectual talents but also predispose them to autism. Sci Am. 2012 Nov;307(5):72-5.----------Sun, X., Allison, C., Auyeung, B., Baron-Cohen, S., & Brayne, C. (2014). Parental concerns, socioeconomic status, and the risk of autism spectrum conditions in a population-based study Research in Developmental Disabilities, 35 (12), 3678-3688 DOI: 10.1016/j.ridd.2014.07.037... Read more »

  • October 21, 2014
  • 07:00 AM
  • 90 views

Not Quite Dead Yet

by Mark E. Lasbury in The 'Scope

History shows that premature burial was more common than people might want to believe. Many burial traditions, including the Irish wake, stem from trying to prevent someone from being buried alive. How might this happen? Several medical conditions can lead to a poor decision on burial time. ... Read more »

Christopher Dibble. (2010) The Dead Ringer: Medicine, Poe, and the fear of premature burial. Historia Medicinae. info:/

  • October 21, 2014
  • 04:53 AM
  • 69 views

Antibiotics and childhood obesity: a weighty correlation

by Paul Whiteley in Questioning Answers

It's been a few weeks since the publication of the paper by L. Charles Bailey and colleagues [1] correlating early multiple exposure to broad spectrum antibiotics with obesity in infancy. On purpose I've left it a while before talking about this research so as to let the scientific dust settle a little and get a flavour for some of the discussions about this research (see here and see here).You're a true vulgarian, aren't you?A few details about the Bailey study first:Looking at the electronic records for a large cohort of children (~65,000), researchers picked out "Treatment episodes for prescribed antibiotics" based on prescription data before the age of 2 years.Anthropometric (growth) data was also determined from visits to healthcare providers between the ages of 2 and 5 years and compared with body mass index (BMI) norms derived from a large US-based survey, NHANES.Results: "Sixty-nine percent of children were exposed to antibiotics before age 24 months" with a rough average of 2 antibiotic prescriptions per child. For those who received 4 or more courses of antibiotics, the risk of obesity during early childhood was slightly elevated (11%) compared with those receiving fewer courses.The authors specifically focused on broad spectrum antibiotics as being correlated with infant weight issues; antimicrobials acting against a broad range of bacteria rather than more targeted pharmaceutics.They concluded: "Repeated exposure to broad-spectrum antibiotics at ages 0 to 23 months is associated with early childhood obesity". That being said, they also noted that various other factors seemed to correlate with infant obesity including: "Steroid use, male sex, urban practice, public insurance, Hispanic ethnicity, and diagnosed asthma or wheezing".I'm also minded to pull in a few other findings which did not get so many media headlines such as the reporting that at 4 years of age, 15% of the cohort were found to be obese and 33% overweight (source here).The Bailey results are interesting insofar as the association being made between early antibiotic use and obesity but, as always, a little caution needs to be applied before reading too much into the findings. I note the BBC coverage of this article mentions limitations: "they were not able to look at the children's weight or exercise regimes" so correlation not necessarily being the same as causation comes into play. I might also add that whilst antibiotic stewardship is still a developing area, many/most antibiotic prescriptions are not just given willy-nilly as any parent with a young child suffering from an ear infection for example, will probably be able to attest.I have kinda talked around this area of antibiotics and weight before on this blog (see here) and the implication that antibiotics, broad spectrum, by their very nature have a pretty profound effect on the trillions of bacterial beasties which inhabit places like the gastrointestinal (GI) tract. Carl Zimmer's post on swallowing a grenade (not literally) is a good starting point. The idea being that as well as helping digest our food, said bacteria (whether individual strains or through a more collective action) might also be able to influence a variety of issues like energy homoeostasis, weight management and even our risk of disease (see here and see here). If I take you back to some work looking at a particular bacterium called Akkermansia muciniphila you might get a flavour for this possible connection with weight in mind (at least in rodents).I'm going to finish with another quote included with the BBC report on the Bailey findings. It comes from an independent commentary of the paper and sums up some important issues arising from reading this work:"It would be a concern if parents took from this that they ought to be reluctant to allow antibiotic use in their children. The key risk factors for childhood obesity are over-consumption of high energy, nutrient-poor foods and lack of exercise."Whilst I would perhaps suggest that 'energy in - energy out' is too simplistic an explanation of weight management issues (see here) I would agree that under the right circumstances, antibiotics still make a valuable contribution to the medicines cabinet, and obesity is, very much, a multi-faceted condition.Music... Stevie Wonder and Superstition.----------[1] Bailey LC. et al. Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA Pediatr. 2014. 29 Sept.----------Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, & DeRusso PA (2014). Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA pediatrics PMID: 25265089... Read more »

Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, & DeRusso PA. (2014) Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA pediatrics. PMID: 25265089  

  • October 20, 2014
  • 04:36 AM
  • 80 views

Reasons for visiting ER by those with autism

by Paul Whiteley in Questioning Answers

ER - Emergency Room - or as we call it here in Blighty Accident & Emergency (A & E), is never a particularly desirable place to visit given the emphasis on illness or injury of yourself or loved one. That being said, staff there do a sterling job sometimes under very stressful circumstances, responding to all-manner of complaints, some of which are life-threatening.The paper by Dorothea Iannuzzi and colleagues [1] sought to identify some of the medical reasons why ER visits were made by people on the autism spectrum. They concluded that, depending on age, epilepsy or seizure-type disorders and "psychiatric conditions" were well represented in cases of autism based on data derived from the US 2010 National Emergency Department database.Realising that epilepsy / seizure-type disorders seem to have more than a passing connection to quite a few cases of autism (see here) and can, in some cases, lead to that most extreme of outcomes (see here), I'm not going to focus any further on this part of the Iannuzzi findings. Rather the finding that: "Psychiatric conditions were primary among ASD individuals aged 12-15 years, accounting for more than 11 % of all visits" merits some further analysis.The findings reported by Kalb and colleagues [2] documenting that: "Thirteen percent of visits among children with ASD [autism spectrum disorder] were due to a psychiatric problem, as compared with 2% of all visits by youths without ASD" provides further evidence for the extent of the Iannuzzi finding. Whilst treading carefully in this area of autism research, one detail stuck out from the Kalb report, whereby ER visits due to psychotic disorders seemed to be increased in likelihood compared to visits by asymptomatic children/youths. This seemed to tie in well with my recent discussions on the observations of Maibing and colleagues [3] and the risk/onset of schizophrenia spectrum disorders following a previous child or adolescent psychiatric diagnosis.Unfortunately, my discussions on the research literature on ER visits and autism do not get any happier as I turn to the body of work looking at suicide attempts and autism, and as per the conclusion from Kato and colleagues [4], "ASDs should always be a consideration when dealing with suicide attempts in adults at the emergency room". Again, I've covered the very sensitive topic of suicide (ideation and attempts) and autism previously on this blog (see here and see here) and as we speak further research has emerged pertinent to this topic [5]. Though sometimes quite uncomfortable to discuss, this collected work emphasises how we all really need to be talking a lot more about this issue and what can be done to divert people away from this most extreme type of behaviour. Admission to the ER - which will often be the first point of contact after such behaviour - could be a good place to start having those discussions.In amongst the literature talking about the ER and autism, there are other details which provide a rather more positive discussion about this topic. Take for example, the paper by Giarelli and colleagues [5] looking at the ways and means ER might be made more comfortable to [some of] those on the autism spectrum. Similarly, the guidance supplied by McGonigle and colleagues [6] talking about ways of managing agitation in the ER for those on the autism spectrum might also be better referenced in this clinical setting. Oh, and a bit more knowledge about medical comorbidities potentially affecting people with autism would probably not go amiss more generally.I should conclude that whilst I've focused on some of the more frequently reported reasons why people with autism might present to the ER, one shouldn't forget that all the other reasons why the general population go to the ER are similarly as pertinent to those on the spectrum. That being said, I very much doubt that "help with removing false nails" would feature on most people's reasons to attend hospital...----------[1] Iannuzzi DA. et al. Brief Report: Emergency Department Utilization by Individuals with Autism. J Autism Dev Disord. 2014 Sep 27.[2] Kalb LG. et al. Psychiatric-related emergency department visits among children with an autism spectrum disorder. Pediatr Emerg Care. 2012 Dec;28(12):1269-76.[3] Maibing CF. et al. Risk of Schizophrenia Increases After All Child and Adolescent Psychiatric Disorders: A Nationwide Study. Schizophr Bull. 2014 Sep 5. pii: sbu119.[4] Kato K. et al. Clinical features of suicide attempts in adults with autism spectrum disorders. Gen Hosp Psychiatry. 2013 Jan-Feb;35(1):50-3.[5] Takar K. & Kondo T. Comorbid atypical autistic traits as a potential risk factor for suicide attempts among adult depressed patients: a case–control study. Annals of General Psychiatry 2014, 13:33.[6] Giarelli E. et al. Sensory stimuli as obstacles to emergency care for children with autism spectrum disorder. Adv Emerg Nurs J. 2014 Apr-Jun;36(2):145-63.[7] McGonigle JJ. et al. Management of agitation in individuals with autism spectrum disorders in the emergency department. Child Adolesc Psychiatr Clin N Am. 2014 Jan;23(1):83-95.----------Iannuzzi DA, Cheng ER, Broder-Fingert S, & Bauman ML (2014). Brief Report: Emergency Department Utilization by Individuals with Autism. Journal of autism and developmental disorders PMID: 25261249... Read more »

Iannuzzi DA, Cheng ER, Broder-Fingert S, & Bauman ML. (2014) Brief Report: Emergency Department Utilization by Individuals with Autism. Journal of autism and developmental disorders. PMID: 25261249  

  • October 19, 2014
  • 01:43 PM
  • 85 views

DNA Nanotech: The First Large DNA Crystals

by Gabriel in Lunatic Laboratories

DNA is the stuff of life as we know it, but it is the potential as a programmable material platform that could spawn entire new and revolutionary nanodevices in computer science, microscopy, biology, and more. Researchers have been working to master the ability to coax DNA molecules to self assemble into the precise shapes and sizes needed in order to fully realize these nanotechnology dreams. A dream that been going on for 20 years now and was just realized.... Read more »

Ke, Y., Ong, L., Sun, W., Song, J., Dong, M., Shih, W., & Yin, P. (2014) DNA brick crystals with prescribed depths. Nature Chemistry. DOI: 10.1038/nchem.2083  

  • October 19, 2014
  • 11:00 AM
  • 90 views

Ten years into the making, the HIV-1 mosaic vaccine finally goes into human trial

by EE Giorgi in CHIMERAS

© Bette Korber et al. I hope you will all forgive me if this week I'm gushing over my amazing mentor Bette Korber, as last week she shared some awesome news on Facebook:"A landmark in my life happened yesterday, a major step in a long story. A decade ago I had an idea for making an HIV vaccine that had the potential to work globally. After a struggle (in my first 2 failed proposals, reviewers declared what I proposed was impossible), I got an internal grant from Los Alamos to develop the idea (third time's a charm). With that funding I could bring together a group of computational people to work together on expressing the idea -- a talented guy named Simon Perkins wrote amazing code to make it so, with computational design suggestions from the group, particularly my husband James Theiler. Then James, Will Fischer, Tanmoy Bhattacharya, and I put it through its paces, optimizing running conditions and devising ways to compare mosaics with natural proteins, with additional help from our friends Karina Yusim, Carla Kuiken and Bob Funkhouser. We called it a mosaic vaccine. After so many years of hard work, and with the collaboration of experimentalists at Harvard and at Duke (Drs. Haynes, Letvin, and Barouch), two weeks ago a phase I safety trial finally opened, and an HIV mosaic vaccine went into the arm of a human volunteer for the very first time. "Safety trial" means that this is just the first phase in testing the safety of the vaccine (I explained the three phases of human trials in this post). We will gather immune responses and we are hoping to see the same good results we saw in monkeys [2-5]. If all goes well, HIV mosaics are in the pipeline for 4 more human vaccine studies. I'm so excited about this study and so proud of my mentor.When I explain to people the challenge we are facing when designing an HIV-1 vaccine, I usually make a very simplistic comparison with the flu virus. Influenza evolves from one season to the next, which is why every year we need a new flu shot. So, basically, the flu evolves into a new virus every year. Well, HIV evolves so rapidly that every person has a different virus. In our database alone we have half a million distinct HIV viral sequences: how can you vaccinate people against half a million different viruses? In the past, successful vaccines against diseases like polio or the measles have been made by taking a real virus, inactivating it (for example, you just take one or two of its proteins, but not the whole virus, to ensure it loses its ability to infect cells), and then injecting it into the body. The immune system "sees" the viral proteins and initiates a response. The response is then "saved" into memory cells, which, next time they encounter the pathogen, will remember how to produce the right response that will promptly clear the virus before it can start an active infection. So, as you can see, the problem with HIV is that the viral population is so diverse that no one virus found in nature will protect people from contracting the infection. How to bypass the obstacle, then? Bette's idea is to basically use a computer that mimics HIV's evolutionary mechanisms to create an in-silico virus [1], something I've discussed in this post. The algorithm takes as input a population of, say, 100 different HIV sequences, and then recombines them creating a new population of artificially constructed viral sequences. HIV viruses can naturally recombine when infecting the same cells, and what the algorithm does is mimic this mechanism making sure that after every recombination step the new sequence is still a viable and functional virus. The computer mimics this process, iterates it multiple times and then the best representative is selected as a potential vaccine.The first caveat is: is this new, artificially constructed sequence a real virus? After all, it was never found in nature. It was created by a computer algorithm. It turns out that when reconstructed in a wet lab, the mosaic proteins are functional and viable.The second hurdle was to prove that these artificially constructed sequences are safe to be used in a vaccine and that they do elicit protective responses against not just a few HIV viruses, but many, many HIV viruses -- enough to prevent infection. So, you get an idea of why the mosaic vaccine took 10 years from concept to the first human trial. Animal studies [2-5] demonstrated that mosaic vaccines elicit good immune responses. In one study in particular [3], compared to controls, vaccinated monkeys required many more challenges to get infected (for a risk reduction of 80%), and once infected, they were able to control the viral load and survive the infection. So, as Bette said, we are hopeful. Hopeful and excited![1] Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD, Hahn BH, & Korber BT (2007). Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nature medicine, 13 (1), 100-6 PMID: 17187074[2] Nkolola JP, Bricault CA, Cheung A, Shields J, Perry J, Kovacs JM, Giorgi E, van Winsen M, Apetri A, Brinkman-van der Linden EC, Chen B, Korber B, Seaman MS, & Barouch DH (2014). Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer. Journal of virology, 88 (17), 9538-52 PMID: 24965452[3] Barouch DH, Stephenson KE, Borducchi EN, Smith K, Stanley K, McNally AG, Liu J, Abbink P, Maxfield LF, Seaman MS, Dugast AS, Alter G, Ferguson M, Li W, Earl PL, Moss B, Giorgi EE, Szinger JJ, Eller LA, Billings EA, Rao M, Tovanabutra S, Sanders-Buell E, Weijtens M, Pau MG, Schuitemaker H, Robb ML, Kim JH, Korber BT, & Michael NL (2013). Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. ... Read more »

Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD.... (2007) Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nature medicine, 13(1), 100-6. PMID: 17187074  

Nkolola JP, Bricault CA, Cheung A, Shields J, Perry J, Kovacs JM, Giorgi E, van Winsen M, Apetri A, Brinkman-van der Linden EC.... (2014) Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer. Journal of virology, 88(17), 9538-52. PMID: 24965452  

Barouch DH, Stephenson KE, Borducchi EN, Smith K, Stanley K, McNally AG, Liu J, Abbink P, Maxfield LF, Seaman MS.... (2013) Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell, 155(3), 531-9. PMID: 24243013  

Barouch DH, O'Brien KL, Simmons NL, King SL, Abbink P, Maxfield LF, Sun YH, La Porte A, Riggs AM, Lynch DM.... (2010) Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nature medicine, 16(3), 319-23. PMID: 20173752  

  • October 18, 2014
  • 02:55 PM
  • 95 views

New Genetic Test to help Solve Rare Disease Diagnosis

by Gabriel in Lunatic Laboratories

My sister suffers from a rare disease which causes small fiber polyneuropathy, or the killing of nerves in her hands and feet. As it progresses she has trouble standing or using her hands. If that was the worst of it, then it might be liveable given the time between severe attacks is years or more. Unfortunately, it also causes intense and mostly constant pain and burning sensations, pain so bad that conventional narcotic painkillers have trouble controlling it. After some time working with the hospital I narrowed it down to autoimmune mediated. Her Doctors finally agreed, but only after first dismissing it as anything from she was faking it, all the way to lupus.... Read more »

Lee, H., Deignan, J., Dorrani, N., Strom, S., Kantarci, S., Quintero-Rivera, F., Das, K., Toy, T., Harry, B., Yourshaw, M.... (2014) Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders. JAMA. DOI: 10.1001/jama.2014.14604  

  • October 18, 2014
  • 09:45 AM
  • 81 views

Immunoglobulin E: not just a bystander in lupus?

by Aurelie in The Immuno Blog

IgE antibodies are mostly known for their pathophysiological role in allergic reactions and in certain immune deficiencies referred to as hyper-IgE syndromes. In a study published in The Journal of Experimental Medicine in September, Dema et al. find that IgE … Continue reading →... Read more »

Dema B, Charles N, Pellefigues C, Ricks TK, Suzuki R, Jiang C, Scheffel J, Hasni S, Hoffman V, Jablonski M.... (2014) Immunoglobulin E plays an immunoregulatory role in lupus. The Journal of experimental medicine. PMID: 25267791  

  • October 18, 2014
  • 09:34 AM
  • 107 views

Merit’s Liquidity

by nooffensebut in The Unsilenced Science

The latest SAT and ACT data suggest that America’s cognitive elite have been enjoying new geographic mobility, but difficult economic times push them out of the elite strata, contrary to a prediction of The Bell Curve by Richard Herrnstein and Charles Murray.... Read more »

nooffensebut. (2014) Parents’ Income is a Poor Predictor of SAT Score. Open Differential Psychology, 1-19. info:other/

  • October 18, 2014
  • 05:30 AM
  • 84 views

More epigenetics, EN-2 and autism... the plot thickens

by Paul Whiteley in Questioning Answers

I don't mind admitting that I was to some extent 'winging it' with my previous post on epigenetics and Engrailed-2 (EN-2) as a consequence of the findings reported by Jill James and colleagues [1] with autism in mind. Although an avid follower of the science of epigenetics when (cautiously) applied to autism, I am by no means any authority on the subject matter particularly when it comes to the nitty-gritty details. You can probably therefore expect similar things in my latest discussions on yet more work from this research group which appeared recently [2].I have only one rule. Everybody fights, no one quits.And so, with that pinch of salt at the ready...The final conclusion made in the most recent James article boils down to the suggestion that "persistent postnatal overexpression of EN-2 suggests that the closing of this programed developmental window may have been missed in some individuals with autism because of epigenetic abnormalities". That being said I think we have quite a way to come before we can substantiate this finding particularly when the main protagonist in the latest article is something called 5-hydroxymethylcytosine (5-hmC) and results which show "that elevated 5-hmC in the EN-2 promoter is associated with a significant decrease in repressive MeCP2 and histone H3K27me3 that appear to over-ride 5-mC hypermethylation". The H3K27me3 bit comes from their previous findings by the way.To most readers that probably sounds as complicated as it first did to me so I will try and explain more.EN-2 as I've talked about in that post on the previous James work, has been linked to cases of autism as per the example of the study by Wang and colleagues [3] linking mutations in this gene to cases of autism. The idea being that mice bred without the gene (the homeobox domain of EN2) show some of the [mouse] signs and symptoms of autism alongside issues with the cerebellum and a reduction in the number of Purkinje cells which have been previously noted in cases of autism [4]. The previous James results in this area reported on hypermethylation of the EN-2 promoter region which would normally equate as gene silencing in epigenetic terms, in line with the more structural genomic issues seen in autism that I've just talked about. But, and it is an important point, when they looked at EN-2 expression and protein levels - function and products of the gene - they actually found that levels were increased in their autism samples despite the methylation mark and its 'stop talking' properties. They noted on that occasion that "transcriptional upregulation by other epigenetic mechanisms predominated over the repressive tendencies of DNA cytosine methylation".Their latest foray into this area sought to further clarify just what might be going on specifically with EN-2 gene-specific DNA hypermethylation previously reported. To do this they focused on both measuring 5-hmC and also 5-methylcytosine (5-mC) among other things based on the same tissue samples (post-mortem cerebellum samples) detailed in their previous study. 5-hmC is apparently an oxidation product of 5-mC mediated via something called TETs.What they found, far from answering the question of a discrepancy between epigenetic gene silencing of EN-2 but increased gene function and products, actually makes the whole thing a lot more complicated. So they observed "a significant increase in both 5-mC and 5-hmC in the autism cerebellum relative to the control samples". Further that there was "a significant increase in 5-hmC content within the upstream EN-2 promoter region" and "a highly significant positive correlation... was found between 5-hmC content and EN-2 gene expression in the 5’ promoter CpG island in autism but not in control samples". They note that: "that 5-hmC accumulation is mechanistically related to gene upregulation" something which I think ties into other work hinting at the demethylating role for 5-hmC [5].Insofar as my mention of MeCP2 and histone H3K27me3 from the latest and previous James reports, I can't really say too much more aside from noting again: "reduced MeCP2-mediated gene repression may have contributed to persistent EN-2 gene overexpression in the autism samples". Actually the authors speculate that MeCP2 binding and histone H3K27 trimethylation might work together in a "repressive" manner but when reduced as they were "may contribute to aberrant overexpression of EN-2 in the autism cerebellum" as per their findings.I have to say that I struggled with getting my head around these findings and I'd quite understand if readers also struggled with my interpretation of them ("If you can't explain something to a six-year-old/granny, you really don't understand it yourself"). I understand that we don't all walk around with our genes stuck in the 'on' or 'off' position and that particularly during foetal and the early post-natal periods, genes are being switched on and off at a surprising rate for many, many different important reasons. I also understand that DNA methylation is an important part of the whole genes switched on or off thing but not the only way that this process can happen as per the authors mention of chromatin and some previous text in this area [6]. With my very limited knowledge of this area, I am however not yet convinced that we have the full story here; specifically in terms of why the original finding of hypermethylation of the EN-2 promotor region (gene silencing) yet increased expression and protein levels were reported. I wonder if indeed we might be able to learn more from a two-hit approach whereby hypermethylation of only one gene allele leaves the other still working?Just before I finish I'd like to also draw your attention to another paper which has started to ask similar questions about 5-hmC and might be contrasted with the recent James paper. Zhubi and colleagues [7] (open-access here) looked at 5-hmC with a couple of other potentially important genes linked to cases of autism (RELN and GAD1) in mind. They reported: "a significant increase in TET1 expression and an enrichment in the level of 5-hmC... at the promoters of GAD1 and RELN in ASD when compared with CON [controls]". Further that their data are: "consistent with the hypothesis that an increase of 5-hmC (relative to 5-mC) at specific gene domains enhances the binding of MeCP2 to 5-hmC and reduces expression of the corresponding target genes... Read more »

  • October 18, 2014
  • 01:42 AM
  • 60 views

Full-term developmet of quail chick by ICSI

by Mizushima S in the Node

The eggs of domestic birds have been used in the study of developmental biology, leading to the extensive accumulation of knowledge on embryonic development. However, the early events involved in bird development, particularly the mechanism underlying fertilization, have not been elucidated in as much detail as those of other species of animals. The ooplasm in […]... Read more »

Mizushima, S., Hiyama, G., Shiba, K., Inaba, K., Dohra, H., Ono, T., Shimada, K., & Sasanami, T. (2014) The birth of quail chicks after intracytoplasmic sperm injection. Development, 141(19), 3799-3806. DOI: 10.1242/dev.111765  

  • October 17, 2014
  • 04:02 PM
  • 105 views

A look at Air Pollution and Your Body

by Gabriel in Lunatic Laboratories

We have all probably seen stories from China on the horrid air pollution there. Accompanying those reports of course are the statistics for air pollution that deaths have caused. For the record, the World Health Organization estimated that ambient air pollution caused 3.7 million premature deaths (worldwide) in 2012 alone – yet what exactly happens to your body when it encounters pollutants?... Read more »

  • October 17, 2014
  • 11:40 AM
  • 83 views

October 17, 2014

by Erin Campbell in HighMag Blog

For years the prettiest cells to image were flat cells in a dish. Thanks to the tireless work of many, beautiful high-resolution images can now come from tissue in a living organism. Today’s image is from a paper showing improved techniques for imaging fine cellular processes within large volumes, from the lab of recent Nobel prize winner, Eric Betzig. A material’s refractive index refers to how light travels through it; the simplest example being how light bends when passed through water. The refractive index heterogeneities stemming from the many cell types, morphologies, and subdomains within a living organism are a challenge to microscopists. As described in a paper from earlier this year, Wang and colleagues improved on previous techniques for imaging within large volumes. Wang and colleagues use adaptive optics (AO), which corrects for the microscope’s aberrations that limit image resolution, in a mode fast enough to correct for the various aberrations within a large sample, without inducing photodamage or photobleaching. The image above shows a 3D rendering from deep within a living zebrafish brain, with oligodendrocytes (magenta) and neuronal nuclei (green) visible.Wang, K., Milkie, D., Saxena, A., Engerer, P., Misgeld, T., Bronner, M., Mumm, J., & Betzig, E. (2014). Rapid adaptive optical recovery of optimal resolution over large volumes Nature Methods, 11 (6), 625-628 DOI: 10.1038/nmeth.2925Adapted by permission from Macmillan Publishers Ltd, copyright ©2014 ... Read more »

Wang, K., Milkie, D., Saxena, A., Engerer, P., Misgeld, T., Bronner, M., Mumm, J., & Betzig, E. (2014) Rapid adaptive optical recovery of optimal resolution over large volumes. Nature Methods, 11(6), 625-628. DOI: 10.1038/nmeth.2925  

  • October 17, 2014
  • 08:55 AM
  • 108 views

People Are More Swayed by Things That Look Sciencey

by Elizabeth Preston in Inkfish

Anyone who’s paged through a women’s magazine will recognize this strategy: to make a product seem better, surround it with a scientific glow. “Clinical trials show lashes grow up to 400% fuller!” “27% reduction of dark spots in 10 weeks!” “Ceramides!” Does this actually help convince people to hand over their cash? A study using […]The post People Are More Swayed by Things That Look Sciencey appeared first on Inkfish.... Read more »

  • October 17, 2014
  • 06:50 AM
  • 84 views

The Friday Five for 10/17/2014

by Bill Sullivan in The 'Scope

Coolest science news stories of the week: stem cells to treat diabetes, fake testes, erasing memories, more!... Read more »

DeMartini DG, Ghoshal A, Pandolfi E, Weaver AT, Baum M, & Morse DE. (2013) Dynamic biophotonics: female squid exhibit sexually dimorphic tunable leucophores and iridocytes. The Journal of experimental biology, 216(Pt 19), 3733-41. PMID: 24006348  

Pagliuca, F., Millman, J., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J., Peterson, Q., Greiner, D., & Melton, D. (2014) Generation of Functional Human Pancreatic β Cells In Vitro. Cell, 159(2), 428-439. DOI: 10.1016/j.cell.2014.09.040  

  • October 17, 2014
  • 05:22 AM
  • 95 views

Altered ghrelin levels in boys with autism

by Paul Whiteley in Questioning Answers

"Honey, it's the '90s, remember?"Saudi Arabia and autism research? It must be at least one author from the research tag-team that is Mostafa and Al-Ayadhi.Indeed, in today's post it is Laila Al-Ayadhi featured on the paper by Felwah S. Al-Zaid and colleagues [1] (open-access) who concluded on: "a potential role for the hormone ghrelin in the pathogenesis of autism".Ghrelin, by the way, is often called the 'hunger hormone' as a result of its effects in relation to energy homoeostasis. Alongside another hormone called leptin (which has also been implicated in cases of autism) the long-and-short of food intake regulation seem to be covered by these hormones [2].The Al-Zaid paper is open-access but I'll direct you to a few important points...A case-control study, authors looked at various measures for 31 boys diagnosed with autism compared with 28 age- and sex-matched controls.Alongside various anthropometric measures, plasma and serum levels of "acyl ghrelin (AG), des-acyl ghrelin (DG), total testosterone (TT), free testosterone (FT), leptin and growth hormone (GH)" were measured. These were single spot measures with samples taken "after an overnight fast". Results: the autism group were on average heavier than controls but aside from that, no other physical measure was significantly different (mean height was greater in the autism group but just escaped significance). Both acyl ghrelin and des-acyl ghrelin levels were significantly lower in the autism group. By contrast, leptin levels were higher in the autism group (as per other independent findings) and free and total testosterone levels were significantly elevated compared to controls. Taking into account the effect of weight and it's link to adiposity, authors also showed that an analysis of a smaller subgroup (autism, n=27; controls, n=28) where mean weight was controlled for, found a similar trend in hormone levels (see this link to Table 3 of the paper) bearing in mind how body fat can influence the parameters.Various correlational analyses were completed on the data but given the relatively small participant groups and the use of spot samples I'm not particularly minded to read too much into these findings at this time.The authors conclude that their study: "contributes significantly to the understanding of hormonal dysregulation in the pathophysiology of autism, as it provides baseline data regarding hormonal profiles in autism and substantiates potential clinical interventions".Small participants numbers and a "lack of female subjects with autism" kinda prohibit me from reading too much into these findings as they stand. I've already made mention of the research trend when it comes to elevated leptin levels and autism (see the paper from Rodrigues and colleagues [3] as one example). Likewise, testosterone levels and autism have received quite a bit of autism research attention down the years (see here). Indeed, elevations in testosterone levels not described in-utero with some potential relationship to foetal programming, has been the stuff of controversy in autism research circles [4].Going back to the primary ghrelin findings and the observations of lower levels detected in their autism group, the authors speculate on some of the hows and whys of their findings. Gastrointestinal (GI) issues get a call-out and how some of the variety of GI issues noted in cases of autism "could affect the gastric mucosa and interfere with the normal function of ghrelin-secreting cells". although no particulars about GI issues are included in their descriptions of their cohort. One additional issue that I would perhaps add to the whole inflammation, dysbiosis et al discussions would be how ghrelin seems to play some role in GI motility [5] too. That being said, 'wide-ranging' is perhaps the best way to describe what biological processes ghrelin might impact on [6].I was a touch surprised that the more usual role for ghrelin in terms of hunger and energy homoeostasis was not given more prominence in the Al-Zaid article on autism. Food and feeding patterns are important topics when it comes to autism as per discussions on the extremes sometimes noted in cases of autism (see here) and the increasingly important issue of weight (see here) (which also seemed to be picked up in the authors' findings). One might speculate that hunger and signals linked to hunger might be similarly tied into at least some of the feeding issues reported in autism?As I seem to do in many discussions these days, I'll reiterate that there is quite a bit more to see and do in research terms on the relationship between ghrelin and related hormones and autism. The additional suggestion from Ghanizadeh [7] about the ghrelin being a "promising therapeutic target for co-occurring autism and epilepsy" might also be worthy of greater inspection.Music to close. Iggy Pop and Lust for Life.----------[1] Al-Zaid FS. et al. Altered ghrelin levels in boys with autism: a novel finding associated with hormonal dysregulation. Sci Rep. 2014 Sep 26;4:6478.[2] Klok MD. et al. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan;8(1):21-34.[3] Rodrigues DH. et al. Changes in Adipokine Levels in Autism Spectrum Disorders. Neuropsychobiology 2014;69:6-10[4] Geier DA. & Geier MR. A prospective assessment of androgen levels in patients with autistic spectrum disorders: biochemical underpinnings and suggested therapies. Neuro Endocrinol Lett. 2007 Oct;28(5):565-73.[5] Greenwood-Van Meerveld B. et al. Ghrelin as a target for gastrointestinal motility disorders. Peptides. 2011 Nov;32(11):2352-6.[6] Delporte C. Structure and physiological actions of ghrelin. Scientifica (Cairo). 2013;2013:518909.[7] Ghanizadeh A. Ghrelin as a promising therapeutic target for co-occurring autism and epilepsy. Epilepsy Behav. 2011 Feb;20(2):420-1.-----------... Read more »

  • October 17, 2014
  • 03:00 AM
  • 78 views

BHD lung cysts are not degenerative, but may cause pneumothorax

by Lizzie Perdeaux in BHD Research Blog

Although 90% of BHD patients develop lung cysts, there is very little information about the natural history of BHD lung cysts. In order to determine how lung cysts change over time, Johannesma et al. (2014a) compared the results of two … Continue reading →... Read more »

Johannesma PC, Houweling AC, van Waesberghe JH, van Moorselaar RJ, Starink TM, Menko FH, & Postmus PE. (2014) The pathogenesis of pneumothorax in Birt-Hogg-Dubé syndrome: A hypothesis. Respirology (Carlton, Vic.), 19(8), 1248-50. PMID: 25302759  

  • October 16, 2014
  • 05:20 PM
  • 117 views

The “New” Roots of our Friends the Mitochondria

by Gabriel in Lunatic Laboratories

Mitochondria, the proverbial “powerhouse” of the cell. Mitochondria are found in virtually all eukaryotic cells, plant or animal and we thought that was pretty much the end of the story. It wasn’t a great explanation but it was Now new research is turning the idea– that our ancestor cells simply “swallowed up” bacterial cells that eventually became mitochondria– on its head.... Read more »

Zhang Wang, & Martin Wu. (2014) Phylogenomic Reconstruction Indicates Mitochondrial Ancestor Was an Energy Parasite . PLoS ONE. info:/10.1371/journal.pone.0110685

  • October 16, 2014
  • 04:18 PM
  • 155 views

Inherited Memories: Too Good To Be True?

by Neuroskeptic in Neuroskeptic_Discover

In December last year, researchers Brian Dias and Kerry Ressler made a splash with a paper seeming to show that memories can be inherited. This article, published in Nature Neuroscience, reported that if adult mice are taught to be afraid of a particular smell, then their children will also fear it. Which is pretty wild. […]The post Inherited Memories: Too Good To Be True? appeared first on Neuroskeptic.... Read more »

  • October 16, 2014
  • 09:40 AM
  • 102 views

Blood. It’s What’s For Dinner.

by Bill Sullivan in The 'Scope

The practice of feeding on blood, known as hematophagy, is actually a lot more common than you might realize.... Read more »

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