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  • January 20, 2015
  • 04:56 AM
  • 75 views

Autism and low vitamin D at birth

by Paul Whiteley in Questioning Answers

Discussions about vitamin D (the 'sunshine' vitamin/hormone) and autism are not unfamiliar to this blog. Just last year (2014) I covered research talking about the possibility of a connection between vitamin D and [some] autism at least three times (see here and see here and see here), possibly more...but in my game, I'm the bad guy, and I live in the garbage.I wouldn't say that I'm an advocate for everything implied by the correlations being made between vitamin D levels and autism given that vitamin D levels have also been linked to everything from depression (see here) to schizophrenia (see here), issues which might also show some passing connection for some people on the autism spectrum (see here for example). But I am interested in how this research area is evolving...And evolving it is, as yet another study has been published on vitamin D and autism, this time from Elisabeth Fernell and colleagues [1] (open-access) based at the University of Gothenburg in Sweden. Examining 25-hydroxyvitamin D (25(OH)D) levels in dried blood spots "taken in the neonatal period for metabolic screening", researchers concluded that: "low prenatal vitamin D may act as a risk factor for ASD [autism spectrum disorder]."Aside from some happiness that the fantastic resource which is the neonatal blood spot is being put to good scientific use with autism in mind (see here), I was particularly interested to read about the findings from this research group given their previous foray in this area (see here) based on the paper from Kočovská and colleagues [2] (open-access). On that occasion they concluded that young adults diagnosed with an ASD were, as a group, quite a bit more likely to present with lower vitamin D levels than siblings, parents and an asymptomatic control group.Back to the Fernell paper, and a few pointers might be in order:"The aim of the present study was to address the emerging hypothesis that low levels of vitamin D at birth increase the risk for ASD." OK.Sibling pairs were used, one child diagnosed with autism, the other "non-ASD affected". Participants were drawn from two samples, a Gothenburg catchment area sample and a "Stockholm Somali group" which have been previously used in a prevalence study of autism in Somali children in Sweden (see here). Those in the know about autism research will perhaps have heard about autism and Somali children a few times before (see here).Participants were coded according to ethnicity into one of three groups: Swedish, Miscellaneous (non-Scandinavian Europe, South America and East Asia) and African/Middle East. This was due to: "well-known ethnic disparity of vitamin D status."Results: "Children to parents of non-Scandinavian ethnicities had lower mean 25(OH)D levels than children to Swedish parents." See the previous point. "The mean 25(OH)D level was lower in children with ASD... than in their siblings." This trend was significant in "the Swedish and Miscellaneous groups, but not in the African/Middle East group." The authors report that season of birth, a potentially important factor in birth vitamin D levels was likely not the primary variable to account for the ASD - non-ASD sibling differences but there were some disparities noted. I would also draw your attention to another comment from the authors: "Since we studied newborn children before diagnosis, our results are definitely unrelated to lifestyle and diet of the individual, although the mother’s lifestyle and other environmental factors cannot be ruled out."Author conclusion: their findings may support: "the hypothesis that developmental vitamin D deficiency during late pregnancy may carry an increased risk of ASD in the child." Alongside, that is, the requirement for further research with larger numbers of participants.I would certainly echo the sentiments of the authors for the need for larger-scales studies of any connection between low pregnancy/birth vitamin D levels and risk of autism. This is however not the first time that this issue has been studied as per my commentary on the results from Whitehouse and colleagues [3] (see here) who based on the use of the Autism-Spectrum Quotient (AQ) (itself the topic of some recent inquiry) concluded that: "Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales" bearing in mind their focus on mums not offspring when assaying for vitamin D.A few further points before I let you go about your business."In this study we did not examine other possible causes for ASD, such as for instance infections during pregnancy." A very important point indeed if one looks at some of the research literature in this area (see here)."Autoimmunity is another possible cause for ASD, which was not investigated. However, as low vitamin D is suggested to contribute to the pathogenesis of autoimmunity... our findings could be relevant in this context as well." Again, another potentially important point raised here on the basis of other research which has brought the issue of autoimmunity into the autism-vitamin D frame (see here). More generally, the issue of autoimmunity and autism is of increasing research interest.Finally, the authors leave us with a tantalising question: "whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD in the offspring"? Before anyone get's ahead of themselves, I think we need quite a bit more discussion and study on this question specific to autism given that more generally vitamin D for pregnant women is seemingly being more frequently indicated.Just one more thing (to coin a phrase)... although no-one really knows the specific hows, whys and wherefores of any vitamin D connection to autism, I'd be minded to suggest that physiological issues such as gut permeability (yes, it is a real thing) might also register on any future research endeavours given data like that from Assa and colleagues [4] adding to an already interesting area (... Read more »

Elisabeth Fernell, Susanne Bejerot, Joakim Westerlund, Carmela Miniscalco, Henry Simila, Darryl Eyles, Christopher Gillberg, & Mats B Humble. (2015) Autism spectrum disorder and low vitamin D at birth: a sibling control study. Molecular Autism. info:/10.1186/2040-2392-6-3

  • January 19, 2015
  • 03:05 PM
  • 105 views

Fear, PTSD, and newly found neural circuits in the brain

by Dr. Jekyll in Lunatic Laboratories

People with anxiety disorders, such as post traumatic stress disorder (PTSD), often experience prolonged and exaggerated fearfulness. Now, an animal study suggests that this might involve disruption of a gradual shifting of brain circuitry for retrieving fear memories. Researchers have discovered in rats that an old fear memory is recalled by a separate brain pathway from the one originally used to recall it when it was fresh.... Read more »

Penzo MA, Robert V, Tucciarone J, De Bundel D, Wang M, Van Aeist L, Varvas M, Parada LF, Palmiter R, He M, Huang ZJ, Li B. . (2015) The paraventricular thalamus controls a central amygdala fear circuit. Nature. DOI: 10.1038/nature13978  

  • January 19, 2015
  • 10:00 AM
  • 69 views

Float like a jellyfish, sting like a bee

by James Dunce in Antisense Science

A brief article describing the mechanism by which jellyfish administer venom via the sub-cellular proteo-machinery that is the nematocyst. Further, I introduce the composition of venoms and describe the mechanism by which mellitin, a toxin found in bee venom, causes haemolysis.... Read more »

  • January 19, 2015
  • 08:00 AM
  • 65 views

Animals can adapt, but not enough to stay ahead of climate change

by Betty Zou in Eat, Read, Science

To better predict how resilient cold-blooded animals are to climate change, Australian researchers at the University of Sydney and the University of Queensland combed through over 4,000 papers looking for data on how ectotherms change their physiology in response to changes in external temperature. They used data from 205 studies published between 1968 and 2012 to generate the largest database on physiological adaptability in cold-blooded animals.... Read more »

  • January 19, 2015
  • 04:28 AM
  • 77 views

Taking care of mum following receipt of an offspring autism diagnosis

by Paul Whiteley in Questioning Answers

The commentary by Elizabeth Karp & Alice Kuo [1] recently published in JAMA brought my attention back to the 2014 findings from Emily Feinberg and colleagues [2] (open-access) reporting on: "positive effects of PSE [problem-solving education] in reducing parenting stress and depressive symptoms during the critical postdiagnosis period" - that is, moves to taking care of maternal mental health after a child receives a diagnosis of autism or autism spectrum disorder (ASD).This is Jessie, the roughest, toughest cowgirl in the whole west.As per the UK National Autistic Society (NAS) guidance: "An autism diagnosis can be difficult to come to terms with" in light of the impact on both parents, siblings and significant others. The guidance continues: "It will take time to learn how to help your child and family cope with day-to-day life. You have the right to feel annoyed or frustrated. It’s hard to remain positive when things don’t go as planned and it is natural to feel upset."Such are the sentiments voiced by many parents as and when a child is diagnosed with autism. Without wishing to demonise or other -ise the label, some groups have talked about a period of 'grief' being associated with receipt of the diagnosis (see here) at the early stages of the journey and the various adjustments that will often need to be made. During such times, parental and sibling physical and mental health can be adversely affected.The Feinberg study is open-access, but a few details might be useful:Mothers of 122 children who had recently received a diagnosis of autism/ASD were the study participants. They were randomly assigned to receive PSE (n=59) or "usual care" (n=63). PSE by the way, is "a manualized cognitive behavioral intervention" which focuses on identifying "a single, measurable problem" to "then proceed through a series of steps that involve goal setting, brainstorming, and evaluating solutions, choosing a solution, and action planning." The authors have some previous research form in this area [3]. Usual care by the looks of things involved the focus on the child and their needs/requirements but nothing "specifically includes parent-focused mental health services."Various measures were analysed according to the use of PSE or usual care including parenting stress "using the Parenting Stress Index Short Form (PSI)", the amount of depressive symptoms experienced and coping style among other things.Results: "At the 3-month follow-up assessment, PSE mothers were significantly less likely than those serving as controls to have clinically significant parental stress." Very good news by all accounts. With regards to depressive symptoms, "the difference by treatment arm in the risk of experiencing clinically significant depressive symptoms approached statistical significance." For scientific puritans, the emphasis is on the word 'approached' rather than 'reached' statistical significance. That being said: "the reduction in mean depressive symptoms was statistically significant" favouring the PSE group.The authors are rightly cautious about their findings, especially when it comes to the need for longer term follow-up of their intervention/non-intervention groups and the suggestion that further inquiry might be needed to identify best-responders. They conclude however: "Despite the limited scope of the present analysis, the findings are encouraging."With all the chatter about autism research becoming truly translational in terms of bringing findings out of the science world and into the real world, this kind of study strikes me as being particularly important. Without trying to get too tangled up in the psychology speak of the mother-child relationship, evidence suggests that family processes and in particular, the mother-child relationship, can have some bearing on outcome when it comes to autism (see here). Caregiver stress and/or depression is likely to impact on such processes and hence, anything that can alleviate any excesses should be cautiously viewed as a positive thing. Stress has also been mentioned in more extreme ways too.That being said, I'm not necessarily advocating that a 'manualized cognitive behaviour intervention' is the be-all-and-end-all of approaching maternal mental health and wellbeing when it comes to autism. There are lots of other ways that this can be [variably] achieved from something like a stress point of view, as per other discussions (see here). Again from the NAS guidance: "Try to get some time on your own to relax, even if it is just to walk the dog or do the washing up, and try not to feel guilty about doing this. Everyone deserves some time out to recharge the batteries." 'Washing up' I might add, is not a mother-only task, but the sentiments of 'stepping back' and keeping home routines as intact as possible are potentially important features of the adaptation phase. Autism research needs to catch-up [4].Now, about paternal health and wellbeing [5] (sorry about the slightly archaic language)...And because today is supposed to be Blue Monday (or not), here's Blue Monday by New Order.----------[1] Karp EA. & Kuo AA. Maternal mental health after a child's diagnosis of autism spectrum disorder. JAMA. 2015 Jan 6;313(1):81-2.[2] Feinberg E. et al. Improving maternal mental health after a child's diagnosis of autism spectrum disorder: results from a randomized clinical trial. JAMA Pediatr. 2014 Jan;168(1):40-6.[3] Feinberg E. et al. Adaptation of problem-solving treatment for prevention of depression among low-income, culturally diverse mothers. Fam Community Health. 2012 Jan-Mar;35(1):57-67.[4] Dykens EM. Family adjustment and interventions in neurodevelopmental disorders. Curr Opin Psychiatry. 2015 Jan 15.[5] Fisman S. & Wolf L. The handicapped child: psychological effects of parental, marital, and sibling relationships. Psychiatr Clin North Am. 1991 Mar;14(1):199-217.----------Feinberg E, Augustyn M, Fitzgerald E, Sandler J, Ferreira-Cesar Suarez Z, Chen N, Cabral H, Beardslee W, & Silverstein M (2014). Improving maternal mental health after a child's diagnosis of autism spectrum disorder: results from a randomized clinical trial. JAMA pediatrics, 168 (1), 40-6 PMID: 24217336... Read more »

  • January 18, 2015
  • 03:06 PM
  • 81 views

Stem cells derived from amniotic tissues have immunosuppressive properties

by Dr. Jekyll in Lunatic Laboratories

Stem cells derived from human amnion have for some time been considered promising for cell therapies because of their ease of access, ability to differentiate, and absence of ethical issues. Now, a research team has found that stem cells derived from human female amnion also have immunosuppressive activity and that the addition of antibodies to specific factors can enhance their immunosuppressive potential.... Read more »

  • January 18, 2015
  • 12:30 PM
  • 69 views

The genetics of Mexico recapitulates Native American substructure and affects biomedical traits.

by Marianna Spatola in genome ecology evolution etc

All figures are reproduced from the original paper (Moreno Estrada et al. Science 2014) Summary and personal comments This paper is about genetic diversity among Native Mexico populations Mexico is an interesting region/subject to study human genetic diversity since it … Continue reading →... Read more »

Moreno-Estrada, A., Gignoux, C., Fernandez-Lopez, J., Zakharia, F., Sikora, M., Contreras, A., Acuna-Alonzo, V., Sandoval, K., Eng, C., Romero-Hidalgo, S.... (2014) The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science, 344(6189), 1280-1285. DOI: 10.1126/science.1251688  

  • January 18, 2015
  • 09:59 AM
  • 90 views

BPA, BPA-free and why Internet titles can be misleading

by EE Giorgi in CHIMERAS

A few years ago, when I still had both kids in preschool, I became painfully aware that plastic is made of oil. I know, I know, where had I been until then? Underground, I guess. All the bottles I'd used to feed milk and drinks to my kids were scratched and chewed and horrid. I screeched in panic, threw them all away and replaced everything with stainless steel. My kids hated the new bottles and refused to take them to school. Yeah, the joys of parenthood.So, imagine my joy when BPA-free came around. Finally something my kids will love and that will not harm them. Except, my friend Cristina sent me the bad news a few days ago: "Dozens of studies link the common plastic chemical bisphenol A (BPA) to all sorts of health problems, including breast and prostate cancers, heart trouble, type 2 diabetes, autism, liver tumors, asthma, infertility, and even obesity. With such a bad track record and hormone-disrupting tendencies, many companies, particularly plastic water bottle manufacturers, have switched to the BPA-free chemical called bisphenol S, or BPS. But a groundbreaking study from University of Calgary researchers suggests we need to diligently avoid both, thanks to newly discovered impacts on the brain [Source]." Aware of the journalistic exaggerations that infest the Web, I logged onto the PNAS website and downloaded the original paper [1], titled: "Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish."Kinch et al. [1] treated embryonic zebrafish (not humans!) with low doses of both BPA and BPS (the compound commonly used in BPA-free products). Apparently, both chemicals are so widespread that, quoting from the PNAS article,"A recent examination of urine samples in the United States and Asia confirmed previous work showing that 93% of people had detectable levels of BPA but surprisingly showed that 81% had detectable levels of BPS, illustrating the wide-spread use of this poorly known bisphenol analog in consumer products [1]." BPA molecules behave as receptor antagonists to sex steroid (estrogen or testosterone): what this means is that they bind to the sex steroid receptors, thus blocking the hormone effect. While the general dosage in plastic bottles may be really low to have any effect on adults, the question as to whether or not they are relevant during embryonic development is indeed well posed since that's the time when the hypothalamus is particularly vulnerable due to lack of blood-brain barrier.The researchers treated the zebrafish embryos with a very low dose for BPA, 1,000-fold lower than the accepted human daily exposure, and then repeated the experiment with the same dosage for BS. They chose the same BPA dose measured in the Oldman River, which serves two major cities in Alberta, Canada. Their results show that BPA exposure in the zebrafish embryos induced hyperactivity and caused precocious neurogenesis in the hypothalamus. Unfortunately, BPS (the BPA-free alternative) wasn't any better, as it still altered brain development and behavior.Two questions popped in my head. First, the researchers immersed the embryos in the contaminants, whereas human embryos are immersed in amniotic fluid, which is always filtered by the placenta, a filter between what circulates in the mother's blood stream and the child's. Given this, did Kinch et al. make a fair comparison? The researchers address the placenta issue, claiming that BPA concentration has been measured in the human placenta and that the dosage used in the experiment was 100-fold lower than circulating levels found in fetal serum.The other question a critical reading of the paper should pose is: how good of a model is the zebrafish embryo for human embryonic development? Especially knowing that zebrafish embryos develop in a mere 72 hours and grow up to a couple of centimeter long, whereas the hypothalamus in the human embryo starts forming around week 8, when it's roughly 1.5 centimeters. It turns out, it is a good model when it comes to embryonic neurogenesis: "Despite the large evolutionary distance between fish and mammals, the overall organization, basic structures, and functional capacities of major hypothalamic components are highly conserved between zebrafish and mammalian brains. [...] In contrast to mammals, zebrafish embryos develop externally and are transparent, and highly amenable to genetic manipulation, making them an ideal vertebrate model for in vivo studies of neural patterning and neuronal specification. As such, zebrafish models have been used extensively in recent years to study the roles played by key signaling pathways in controlling the development of hypothalamic neurons [2]." Having addressed in a satisfactory way my two main concerns with the PNAS paper [1], I particularly like the two points the researchers make in the discussion section. The first one is that the way tolerable levels are determined is using a linear model, starting from the highest possible dose and gradually lowering until no effect is detected. Kinch et al. rightfully argue that dose-response relationships are hardly ever linear when it comes to endocrine-disrupting compounds like BPA and BPS.Second, the researchers claim that the switch from BPA to BPS was done without adequate toxicology testing. What if it turns out that BPS is comparable to BPA in terms of damaging potential?BPA and BPS aside, I wanted this post to also make a case for critical thinking. I'm seeing way too much junk on the Internet being passed for science when in fact it's just bad reporting/journalism (in genetics in particular!!). While the Internet article my friend sent me didn't make any incorrect statement, and it did discuss the actual study a few paragraphs into the article, still, the title, "Popular 'BPA-Free' Chemical Causes Brain Damage, Study Finds" had me frowning because it lacks to mention two fundamental points: 1) the study was conducted on zebrafish (not on humans!) and 2) the supposed brain damage was on the zebrafish embryos (not on humans, and not on children or adults). In fact, let me open a quick parenthesis and cite some numbers a friend of mine posted on Facebook: a paper on some break-through research on Alzheimer's published by the Journal of Clinical Investigation titled "Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease..." got shared 116 times. Stanford posted the story under the title "Blocking receptor in brain’s immune cells counters Alzheimer’s in mice, study finds" and got shared almost 10,000 times. The Telegraph titled its piece "Has Stanford University found a cure for Alzheimer's disease?" and got almost 50,000 shares. But at the very top of the sharing contest came Rod D. Martin  (over 130,000 shares) with the title "Happy New Year! Stanford May Have Just Cured Alzheimer’s" .Bottom line 1: yeah, you can get very popular when you blow up science.Bottom line 2: if you want to draw some useful conclusions from any pseudo-sceintifc news, go back to the source before getting too excited and/or too alarmed.The zebrafish experiment indicates that compounds containing BPA and BPS could potentially harm the fetus and as a safety precaution it recommends pregnant women to steer away from plastic bottles, but it doesn't present any evidence on the effects on children or (non-pregnant) adults. It does not conclude that BPA and/or BPS exposure has the same effect in humans, but it does pose a foundation for further studies as it raises a flag that there may be a risk associated to these chemicals. The way to further validate this hypothesis would be to measure BPA and BPS levels in the urine of pregnant women and then follow the babies' neurological development for a few years to see if the women with higher levels had problematic children compared to the women with lower levels.Of course, it's still a good idea to avoid plastic and use it only when other alternatives aren't handy. Plastic use has certainly increased exponentially in the past few decades and it's a good idea to reduce its use anyways, since it could not only be potentially harmful for our bodies, but it's also definitely bad for the environment. As in all things, cautiousness (whether it's used to avoid plastic or to avoid Internet content) is the best measure for a happy living. [1] ... Read more »

Machluf, Y., Gutnick, A., & Levkowitz, G. (2011) Development of the zebrafish hypothalamus. Annals of the New York Academy of Sciences, 1220(1), 93-105. DOI: 10.1111/j.1749-6632.2010.05945.x  

  • January 17, 2015
  • 05:25 AM
  • 89 views

What can physical activity do for ADHD?

by Paul Whiteley in Questioning Answers

In answer to the question posed in the title of this post, I might refer you to the paper by Susanne Ziereis & Petra Jansen [1] who concluded that results of their research study looking at the impact of two 12-week training programs "support the hypothesis that long-term PA [physical activity] has a positive effect on executive functions of children with ADHD [attention-deficit hyperactivity disorder]."That's the funny thing about birthdays, they're kind of an annual thing.With an important starting point that "non-pharmacologic treatment methods would be preferred by parents, children and psychiatrists" when it comes to treating/managing ADHD and its various symptoms, researchers decided to examine whether one or both of two training programs - "a training which focused on the abilities ball handling, balance and manual dexterity" (EG1 group; n=13) and training "in sports without a specific focus" (n=14) - might improve cognitive performance in children diagnosed with ADHD. Said training regimes were compared against a control group (EG2 group; n=16) where no such intervention was used.Their results based on "assessments of working memory (WM) and motor performance before, immediately after the first training week and one week after the last session" suggested that there may indeed be some merit in physical activity when it comes to various facets of cognitive performance in their cohort. "After the 12-week intervention period, several measures of the EG1 and EG2s significantly improved over time". The no-intervention control group did not fare as well.This is of course not the first time that physical activity has been suggested to impact on executive functions as per the mega-review by John Best [2] (open-access). I might also throw in a link to a piece I wrote on this blog last year (2014) on the potential benefits of something like kata training when it comes to psychology and behaviour (see here) as another example where one might expect similar positive changes. I'm also minded to point you to the paper by Halleland and colleagues [3] suggesting we should be looking a little harder for those with ADHD and executive function issues who might benefit from such interventions.It seems that alongside the very obvious physical benefits to be derived from staying active, mind and behaviour also seem to benefit. A sedentary childhood it seems, does little good to anyone. And since we're on the topic of complementary interventions potentially useful for some cases of ADHD, how about looking at nutrition (see here and see here) as well as exercise?Some music now to complement any activity you might want to try... You Shook Me All Night Long by AC/DC.----------[1] Ziereis S & Jansen P. Effects of physical activity on executive function and motor performance in children with ADHD. Res Dev Disabil. 2015 Jan 2;38C:181-191.[2] Best JR. Effects of Physical Activity on Children’s Executive Function: Contributions of Experimental Research on Aerobic Exercise. Developmental review : DR 2010;30(4):331-551.[3] Halleland HB. et al. Occupational Status Is Compromised in Adults With ADHD and Psychometrically Defined Executive Function Deficits. J Atten Disord. 2015 Jan 2. pii: 1087054714564622.----------Ziereis S, & Jansen P (2015). Effects of physical activity on executive function and motor performance in children with ADHD. Research in developmental disabilities, 38C, 181-191 PMID: 25561359... Read more »

  • January 16, 2015
  • 03:41 PM
  • 98 views

New genetic clues in fragile x syndrome

by Dr. Jekyll in Lunatic Laboratories

Scientists have gained new insight into fragile X syndrome — the most common cause of inherited intellectual disability — by studying the case of a person without the disorder, but with two of its classic symptoms.... Read more »

Myrick LK, Deng PY, Hashimoto H, Oh YM, Cho Y, Poidevin MJ, Suhl JA, Visootsak J, Cavalli V, Jin P.... (2015) Independent role for presynaptic FMRP revealed by an FMR1 missense mutation associated with intellectual disability and seizures. Proceedings of the National Academy of Sciences of the United States of America. PMID: 25561520  

  • January 16, 2015
  • 06:10 AM
  • 92 views

Fixing ‘Leaky’ Blood Vessels in Severe Respiratory Ailments and Ebola

by Jalees Rehman in The Next Regeneration

When you get an infection, your immune system responds with an influx of inflammatory cells that target the underlying bacteria or viruses. These immune cells migrate from your blood into the infected tissue in order to release a cocktail of pro-inflammatory proteins and help eliminate the infectious threat.

During this inflammatory response, the blood vessel barrier becomes “leaky.” This allows for an even more rapid influx of additional immune cells. Once the infection resolves, the response cools off, the entry of immune cells gradually wanes and the integrity of the blood vessel barrier is restored.... Read more »

Gong, H., Rehman, J., Tang, H., Wary, K., Mittal, M., Chatturvedi, P., Zhao, Y., Komorova, Y., Vogel, S., & Malik, A. (2015) HIF2α signaling inhibits adherens junctional disruption in acute lung injury. Journal of Clinical Investigation. DOI: 10.1172/JCI77701  

  • January 16, 2015
  • 04:52 AM
  • 99 views

The gut and 15q Duplication Syndrome

by Paul Whiteley in Questioning Answers

"The results indicate that GI [gastrointestinal] symptoms are common in Dup15q syndrome and may have an atypical presentation."Let's just say I'm Frankenstein's monster. And I'm looking for my creator.That was the conclusion reached in the paper by Elias Shaaya and colleagues [1] following a review of medical records for a small-ish group of participants diagnosed with chromosome 15q duplication syndrome (dup15q syndrome), a genetic condition "involving copy number gains of the maternal chromosome 15q11.2-q13 region." Dup15q syndrome can manifest in a variety of ways including the presence of seizure disorders, poor muscle tone (hypotonia), issues with growth and neurodevelopmental issues.Authors reported functional GI symptoms to be present in over three-quarters of their cohort, slightly varying in frequency depending on the nature of duplication (isodicentric vs. interstitial duplication) recorded. "The most commonly reported symptoms were gastroesophageal reflux (56.7%) and constipation (60%), with 30% of subjects reporting both" and: "Behaviors such as irritability and aggressiveness improved with treatment of GI symptoms in several subjects."Why am I talking about dup15q syndrome on a blog that is supposed to be concentrating on autism research?Well, three reasons: first, dup15q syndrome shares some overlap with the presentation of autism/autistic traits in the more general sense as per other commentaries on the topic (see here and see here). Second, the Shaaya study represents a second research foray into GI issues associated with genetic conditions with autism mentioned as part of some presentation, as per the discussions last year (2014) on GI issues appearing alongside 22q11.2 deletion syndrome (see here). Finally, dup15q has been mentioned on this blog before with the curious findings reported by Mitchell and colleagues [2] who implied that: "specific POPs [persistent organic pollutants] may predispose to genetic copy number variation of 15q11-q13." That last reason ties into my interest in how genes and environment [variably] intersect when it comes to health and wellbeing particularly associated with behaviourally-defined diagnoses.The comment about how treatment of GI symptoms seemed to tie into a reduction in certain 'challenging behaviours' in cases of dup15q syndrome is also worthy of further promotion. As per my review of autism research in 2014, functional GI issues associated with quite a few cases of autism was an ascendancy topic of investigation, further compounded by papers such as the one from Zainab Ridha and colleagues [3] (see here) on autism being one of a number of "useful predictors of STC and FFR [slow transit constipation and functional fecal retention] in children." Alongside other research suggesting that issues such as anxiety and sensory 'over-responsivity' might also tie into the presentation of GI problems in autism (see here), one might see how management/treatment of bowel issues may very well impact on some behaviours. No-one likes to walk around with chronic constipation.I know the Shaaya paper was based on a relatively small number of participants, so it is perhaps implied that further studies are needed to see how generalised GI issues might be in relation to dup15q syndrome. As per that Giardino study [4] on GI involvement in 22q11.2 deletion syndrome (del22), one wonders whether looking at things like "antigliadin (AGA) IgA and IgG, and antitissue transglutaminase (anti-TGase) titers" might also be a useful next step, alongside horror of horrors, the presence of any "abnormal intestinal permeability"?Prefab Sprout - The King of Rock 'N' Roll to close.----------[1] Shaaya EA. et al. Gastrointestinal Problems in 15q Duplication Syndrome. European Journal of Medical Genetics. 2015. January 5.[2] Mitchell MM. et al. Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environ Mol Mutagen. 2012 Oct;53(8):589-98.[3] Ridha Z. et al. Predictors of slow colonic transit in children. Pediatr Surg Int. 2014 Dec 31.[4] Giardino G. et al. Gastrointestinal involvement in patients affected with 22q11.2 deletion syndrome. Scand J Gastroenterol. 2014 Mar;49(3):274-9.----------Shaaya, E., Pollack, S., Boronat, S., Davis-Cooper, S., Zella, G., & Thibert, R. (2015). Gastrointestinal Problems in 15q Duplication Syndrome European Journal of Medical Genetics DOI: 10.1016/j.ejmg.2014.12.012... Read more »

Shaaya, E., Pollack, S., Boronat, S., Davis-Cooper, S., Zella, G., & Thibert, R. (2015) Gastrointestinal Problems in 15q Duplication Syndrome. European Journal of Medical Genetics. DOI: 10.1016/j.ejmg.2014.12.012  

  • January 15, 2015
  • 02:25 PM
  • 124 views

Scientists use the brain to direct fat burning

by Dr. Jekyll in Lunatic Laboratories

Does it seem like no matter what you do, you still can’t shed the pounds? You know what to eat, how to eat and workout regularly, but the weight just won’t go away, well you may not be alone. There are many different medical conditions that limit your ability to lose weight, but thankfully science has now found how to use your brain to shed the weight.... Read more »

Dodd, G., Decherf, S., Loh, K., Simonds, S., Wiede, F., Balland, E., Merry, T., Münzberg, H., Zhang, Z., Kahn, B.... (2015) Leptin and Insulin Act on POMC Neurons to Promote the Browning of White Fat. Cell, 160(1-2), 88-104. DOI: 10.1016/j.cell.2014.12.022  

  • January 15, 2015
  • 01:56 PM
  • 83 views

KSHV and autophagy: vFLIP, v-CyclinD, and v-Bcl2

by thelonevirologist in Virology Tidbits

Deregulation of autophagy isnot limited to cells infected with viruses or bacteria but can also be observed in human cancers. In the context of infection of cells with oncogenic viruses, interference with the autophagy pathway has been documented for proteins derived from a variety of oncogenic viruses, including but not limited to proteins encoded by Human T-Cell Leukemia/Lymphoma Virus-1 (HTLV-1), JC virus (JCV), BK polyomavirus (BKPyV), Epstein-Barr virus (EBV), Kaposi’s Sarcoma-Associated Herpesvirus (KSHV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV). Akin to the infection of cells with positive strand RNA viruses, the induction of autophagy can have positive effects (e.g. BKPyV) or negative effects (e.g. JCV) on viral replication. Since the expression of viral oncoprotein commonly also induces the DNA damage response and thus might promote autophagy via increasing the expression of pro-autophagy genes in a p53-dependent manner, oncogenic viruses the regulation of autophagy might contribute to the transformation of cells both in vitro and in vivo.
Kaposi Sarcoma- Associated Herpesvirus (KSHV) - also known as Human Herpesvirus 8 (HHV8) - is the causative agent of Kaposi’s Sarcoma (KS), a cancer associated with prominent cutaneous lesions. Being a Herpesvirus, KSHV is a large dsDNA virus with genome of approx. 165 kb in size. Here the interference of KSHV with the autophagy pathway is discussed.... Read more »

Silva LM, & Jung JU. (2013) Modulation of the autophagy pathway by human tumor viruses. Seminars in cancer biology, 23(5), 323-8. PMID: 23727156  

Bouley SJ, Maginnis MS, Derdowski A, Gee GV, O'Hara BA, Nelson CD, Bara AM, Atwood WJ, & Dugan AS. (2014) Host cell autophagy promotes BK virus infection. Virology, 87-95. PMID: 24889228  

Pekkonen P, Järviluoma A, Zinovkina N, Cvrljevic A, Prakash S, Westermarck J, Evan GI, Cesarman E, Verschuren EW, & Ojala PM. (2014) KSHV viral cyclin interferes with T-cell development and induces lymphoma through Cdk6 and Notch activation in vivo. Cell cycle (Georgetown, Tex.), 13(23), 3670-84. PMID: 25483078  

Wirawan E, Lippens S, Vanden Berghe T, Romagnoli A, Fimia GM, Piacentini M, & Vandenabeele P. (2012) Beclin1: a role in membrane dynamics and beyond. Autophagy, 8(1), 6-17. PMID: 22170155  

Lee JS, Li Q, Lee JY, Lee SH, Jeong JH, Lee HR, Chang H, Zhou FC, Gao SJ, Liang C.... (2009) FLIP-mediated autophagy regulation in cell death control. Nature cell biology, 11(11), 1355-62. PMID: 19838173  

Liang Q, Chang B, Brulois KF, Castro K, Min CK, Rodgers MA, Shi M, Ge J, Feng P, Oh BH.... (2013) Kaposi's sarcoma-associated herpesvirus K7 modulates Rubicon-mediated inhibition of autophagosome maturation. Journal of virology, 87(22), 12499-503. PMID: 24027317  

Huang X, Wu Z, Mei Y, & Wu M. (2013) XIAP inhibits autophagy via XIAP-Mdm2-p53 signalling. The EMBO journal, 32(16), 2204-16. PMID: 23749209  

  • January 15, 2015
  • 12:00 PM
  • 101 views

Deworming treatments and microbial infections: good for you, not so good for everyone else

by Betty Zou in Eat, Read, Science

In this study, Drs. Ezenwa and Jolles have shown that when it comes to microbial co-infections, anthelmintic treatments are a double-edged sword. The individual benefits of treatment need to be carefully weighed against the potential costs to the population, an important consideration given that anthelmintic treatments are currently being considered as strategies to help manage chronic infections like HIV/AIDS and tuberculosis.... Read more »

  • January 15, 2015
  • 09:15 AM
  • 107 views

2-7 Offsuit: Is Cancer Just "Bad Luck"?

by Bill Sullivan in The 'Scope

A controversial new study suggests that most cancer is just a matter of "bad luck". Is it?... Read more »

  • January 15, 2015
  • 05:10 AM
  • 102 views

Maternal thyroid autoantibody and offspring autism risk

by Paul Whiteley in Questioning Answers

I have, on this blog, previously mentioned the paper by Alan Brown and colleagues [1] suggesting that: "The prevalence of maternal TPO-Ab+ [thyroid peroxidase antibody] was significantly increased in pregnancies giving rise to autism cases (6.15%) compared to controls (3.54%)." It was during some discussion on the suggested diagnosis of Down syndrome disintegrative disorder (see here) and the idea that some signs and symptoms of regressive autism (?) might overlap with TPO antibodies in some cases of Down syndrome.You've got a playdate with destiny!I've had a few weeks to further reflect on the Brown paper and decided that their suggestion of: "the first biomarker-based evidence that a class of known maternal autoimmune disorders is related to autism in offspring" is worthy of a post all of its own.A quick recap first: thyroid peroxidase antibodies translates as the body mounting an immune response against thyroid peroxidase, an important enzyme in the production of the thyroid hormones. As per another mention of TPO based on research suggestive of a tentative link between anti-TPO antibodies and [some] depressive disorder (see here), the more usual clinical occasion regarding detection of such antibodies is in relation to something like Hashimoto's thyroiditis, an autoimmune condition.Brown and colleagues drew upon collected data from the Finnish Prenatal Study of Autism (FiPS-A) [2], an initiative which had at its disposal "archived maternal serum specimens from virtually the entire pregnant population of Finland beginning in 1983". Alongside quite a bit of other registry based information on things like an ICD-10 diagnosis of autism in offspring, Brown et al set to work analysing those archived serum specimens for some "967 matched case-control pairs" (autism cases matched 1:1 with sex and date of birth linked asymptomatic controls) for the presence of thyroid peroxidase antibody (TPO-Ab).As per the previous sentence, serum samples from mums who went on to have a child with autism were significantly more likely to present with TPO-Ab; indeed: "The odds of autism were increased by nearly 80% among offspring of mothers who were TPO-Ab+ during pregnancy" compared with those antibody negative. Perhaps just as important, authors also reported that: "Measures of maternal thyroid hormones did not differ between groups" suggesting that the actual antibodies might be the more important factor over and above a thyroid hormone link (see here for discussion on other work in this area).For those who follow this blog, the idea that [some] autism and [some] autoimmunity / autoimmune conditions might show [some] linkage is not a new one. If one delves deeper into the peer-reviewed research arena one finds other hints that other maternal antibodies might also show a connection to offspring autism risk as per the idea of MAR autism (see here), that is, maternal autoantibody-related autism. Granted, the research road has not run entirely smoothly when it comes to any possible connection (see here) and there are still questions to be answered, not least when it comes to the effects of comorbidity common to autism and how they may likewise have an autoimmune connection too (see here for example). The Brown results however cannot be readily brushed under the scientific carpet given their origin and pretty powerful participant numbers used in the current study alongside some prior research 'form in the inflammatory area (see here). I for one, am keenly awaiting further investigations perhaps including a study or two on offspring autism risk among mothers with autoimmune thyroiditis [3]...?To close: California Über Alles. Let moshing commence...----------[1] Brown AS. et al. Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:86-92.[2] Lampi KM. et al. Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A): overview and design. J Autism Dev Disord. 2011 Aug;41(8):1090-6.[3] Molloy CA. et al. Familial autoimmune thyroid disease as a risk factor for regression in children with Autism Spectrum Disorder: a CPEA Study. J Autism Dev Disord. 2006 Apr;36(3):317-24.----------Brown, A., Surcel, H., Hinkka-Yli-Salomäki, S., Cheslack-Postava, K., Bao, Y., & Sourander, A. (2015). Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort Progress in Neuro-Psychopharmacology and Biological Psychiatry, 57, 86-92 DOI: 10.1016/j.pnpbp.2014.10.010... Read more »

Brown, A., Surcel, H., Hinkka-Yli-Salomäki, S., Cheslack-Postava, K., Bao, Y., & Sourander, A. (2015) Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 86-92. DOI: 10.1016/j.pnpbp.2014.10.010  

  • January 14, 2015
  • 06:18 PM
  • 115 views

Pooping to evolve: how feces allowed us to exist

by Piter Boll in Earthling Nature

by Piter Kehoma Boll Billions of years ago, when the first lifeforms appeared on Earth, our planet was very different from what it is today. Oxygen, so essential for our survival, was not present in the atmosphere. Thanks to the … Continue reading →... Read more »

Holland, H. (2006) The oxygenation of the atmosphere and oceans. Philosophical Transactions of the Royal Society B: Biological Sciences, 361(1470), 903-915. DOI: 10.1098/rstb.2006.1838  

Turner, J. T. (2002) Zooplankton fecal pellets, marine snow and sinking phytoplankton blooms. Aquatic Microbial Ecology, 57-102. info:/

  • January 14, 2015
  • 03:54 PM
  • 119 views

The hidden neurological impact of explosions on military members

by Dr. Jekyll in Lunatic Laboratories

More bad news for war Veterans, the brains of some Iraq and Afghanistan combat veterans who survived blasts from improvised explosive devices (IEDs) and died later of other causes show a distinctive honeycomb pattern of broken and swollen nerve fibers throughout critical brain regions, including those that control executive function. The pattern is different from brain damage caused by car crashes, drug overdoses or collision sports, and may be the never-before-reported signature of blast injuries suffered by soldiers as far back as World War I.... Read more »

Ryu J, Horkayne-Szakaly I, Xu L, Pletnikova O, Leri F, Eberhart C, Troncoso JC, & Koliatsos VE. (2014) The problem of axonal injury in the brains of veterans with histories of blast exposure. Acta neuropathologica communications, 2(1), 153. PMID: 25422066  

  • January 14, 2015
  • 03:43 PM
  • 97 views

Nature's Drag Queens

by Jente Ottenburghs in Evolutionary Stories

Some men like to dress up like females. But do you find drag queens in other species? It turns out Nature has some surprises up her sleeves.... Read more »

Norman, M., Finn, J., & Tregenza, T. (1999) Female impersonation as an alternative reproductive strategy in giant cuttlefish. Proceedings of the Royal Society B: Biological Sciences, 266(1426), 1347-1349. DOI: 10.1098/rspb.1999.0786  

Slagsvold, T. . (1991) Evolution of Plumage Color in Male Pied Flycatchers (Ficedula hypoleuca): Evidence for Female Mimicry. Evolution, 45(4), 910-917. info:/

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