Researchers recently announced the discovery of a frog whose groin flashes orange to scare away predators! The species was discovered in Australia.
When biologist Simon Clulow spotted a frog with an unusual marble pattern on its belly, he knew it could be a new species. If that turned to be true, it would be very surprising as the sighting took place on land close to an airport and not some ... Read more »
CLULOW, S., ANSTIS, M., KEOGH, J., & CATULLO, R. (2016) A new species of Australian frog (Myobatrachidae: Uperoleia) from the New South Wales mid-north coast sandplains. Zootaxa, 4184(2), 285. DOI: 10.11646/zootaxa.4184.2.3
The paper by Nahit Motavalli Mukaddes and colleagues  provides some important, if small-scale, information when it comes to that still controversial term - optimal outcome - with the diagnosis of autism in mind. Optimal outcome basically refers to a particular 'type' of autism whereby following a definite diagnosis of autism or autism spectrum disorder (ASD), a later re-evaluation of signs and symptoms reveals that diagnostic thresholds are subsequently not reached and/or exceeded and hence, the criteria for autism are not fulfilled.I say this is a controversial term because it is. Still after quite a bit of peer-reviewed published research saying 'yes, it exists' (and alongside quite a few manifestations of autism) coupled with quite a bit of research talking about different developmental trajectories accompanying different 'types' of autism (see here) the old 'they weren't really autistic' phrase still comes out time and time again. And with it, children/adults who were diagnosed with autism are doubted to have been actually autistic. The skills of the professionals who made the diagnosis are doubted. The parents and significant others who most likely initiated the screening and diagnosis of autism are doubted. All of this seemingly to uphold the 'lifelong' tag that accompanies quite a bit of discussion about autism. Not a great state of affairs eh?Work by Mukaddes et al has previously made an appearance on this blog (see here) talking about possible predictors of optimal outcome. This time around they aimed to "assess the autism symptoms and other psychiatric disorders in a group of children with a past history of autism." Their group, comprised of 26 who "lost the diagnosis of autism two to eight years previously", were assessed for autism - DSM-5 autism no less - together with various other psychometric/behavioural schedules.Results: "None of the participants met criteria for an autism diagnosis." What this means is that for their cohort, 'loss' of a diagnosis of autism was not some short-term thing. But be careful here, as I remind you that DSM-5 criteria "were used for [a] diagnosis of ASD" for autism and the emerging data suggesting that DSM-5 is already likely to move quite a few people off the autism spectrum compared with previous diagnostic schedules (see here). Indeed, I wonder how many of their cohort might be labelled with SCD instead?When it came however to looking at other psychiatric/behavioural labels, being an optimal outcomer with autism in mind did not necessarily mean symptom-free: "81% had a present psychiatric disorder based on the K-SADS. ADHD [attention-deficit hyperactivity disorder], specific phobia and Obsessive Compulsive Disorder (OCD) were the most common disorders." This finding is interesting. Interesting because it does not necessarily tally with other work on this topic (see here) but at the same time, reiterates that a diagnosis of autism rarely exists in a diagnostic vacuum (see here) (and that includes past diagnoses of autism). That ADHD in particular, is a label of growing importance to quite a few cases of autism should also be mentioned (see here) as should be the 'effects' that such a label has been linked with (see here)."It is crucial to maintain psychiatric follow up of children who move-off ASD." Wise words from Mukaddes and colleagues but given the state of things here in Blighty, with continued austerity and long, long wait lists for assessments (see here), I don't really have a great deal of confidence that removal from the autism spectrum is going to prompt much in the way of follow-up. Indeed, going back to the question of whether optimal outcomers might nevertheless hit SCD - 'autism lite' - diagnostic thresholds, I'm not even sure that those fitting into the SCD description are going to receive anything like the services and support they will still no doubt require. I do hope that I am wrong but...---------- Mukaddes NH. et al. What Happens to Children Who Move off the Autism Spectrum? A Clinical Follow-Up Study. Pediatrics Int. 2016. Nov 12.----------Motavalli Mukaddes, N., Mutluer, T., Ayik, B., & Umut, A. (2016). What Happens to Children Who Move off the Autism Spectrum? A Clinical Follow-Up Study Pediatrics International DOI: 10.1111/ped.13202... Read more »
Motavalli Mukaddes, N., Mutluer, T., Ayik, B., & Umut, A. (2016) What Happens to Children Who Move off the Autism Spectrum? A Clinical Follow-Up Study. Pediatrics International. DOI: 10.1111/ped.13202
Note: the “Life in the Lab” series features interviews of interns and visitors. This post is by our second 2016 OMA Visiting Fellow Tunca Doğan, who spent a month with us earlier this year. You can follow Tunca on Twitter at @tuncadogan. —Christophe
Please introduce yourself in a few sentences.
My name is Tunca Doğan. I received my PhD in 2013 with a thesis study in the fields of bioinformatics and computational biology where we developed methods for the clustering of the protein sequences using unsupervised machine learning techniques (Dogan and Karacali, 2013). I’ve since been working as a post-doctoral fellow in the EMBL-EBI, UK under the Protein Function Development team (UniProt Database) leaded by Dr Maria Martin. Here I’m developing new tools and methods for the automated functional annotation of protein records in the UniProtKB using a variety of features including domain architectures (Dogan et al., 2016). I’m also conducting research in the field of computational drug discovery. As of 2016, I’m also affiliated to the Department of Health Informatics, METU, Turkey both as a senior research fellow and a faculty candidate.... Read more »
Doğan T, & Karaçalı B. (2013) Automatic identification of highly conserved family regions and relationships in genome wide datasets including remote protein sequences. PloS one, 8(9). PMID: 24069417
Doğan T, MacDougall A, Saidi R, Poggioli D, Bateman A, O'Donovan C, & Martin MJ. (2016) UniProt-DAAC: domain architecture alignment and classification, a new method for automatic functional annotation in UniProtKB. Bioinformatics (Oxford, England), 32(15), 2264-71. PMID: 27153729
The paper by Wenjie Sun and colleagues  (open-access) provides the blogging fodder for today's post and although based on the science of epigenetics, the usual suspect - DNA methylation - gives way to another concept: histone acetylation with autism in mind. Before heading into the paper myself, I'll draw your attention to some other write-ups of the study including a hat-tip to Jeff Craig and his piece on the topic (see here).So histone acetylation... I've covered the subject before on this blog (see here) but basically DNA, the stuff that carries the genetic blueprint, complexes with histones to form something called nucleosomes. It's a combination likened to thread wrapped around a spool. Continuing that thread wrapped around a spool analogy, protruding threads called histone tails can be modified in a chemical sense (via processes such as acetylation where an acetyl group is added or deacetylation where one is removed) which can subsequently affect genetic transcription.Still with me? Good. Sun and colleagues set out to look at histone acetylation in the context of autism; specifically in post-mortem brain samples donated from those deceased who were diagnosed with autism and whether they might show some important changes based on the use of "a histone acetylome-wide association study (HAWAS)."Specific areas of the brain were assessed using the HAWAS approach - "prefrontal cortex (PFC), temporal cortex (TC), and cerebellum (CB)" - and researchers were looking for a specific type of acetylation mark called H3K27ac linked to gene activation. Based on brain samples from 94 participants ("45 ASD [autism spectrum disorder], 49 control"), a few details emerged:Despite the expected heterogeneity across the presentation of autism in terms of whether the diagnosis of autism was syndromic (secondary to an existing condition) or non-syndromic (idiopathic), the authors reported that approaching 70% of the autism cases "shared a common acetylome signature at >5,000 cis-regulatory elements in prefrontal and temporal cortex." In other words, a not uncommon molecular signature in relation to histone acetylation seemed to be present in quite a few of the participant samples included for study.Although one needs to be a little cautious about making grand, sweeping claims about how such an 'acetylome signature' comes about, the authors reported "that ASD-specific differential acetylation is driven mostly by.. factors such as environmental influences, SNPs in trans (at a different locus), indels, and larger chromosomal variants." Note the term 'environmental influences' (something I'll come back to shortly).When it came to what types of genes were potentially being 'affected' by acetylation, the authors report on quite a diverse spread "involved in synaptic transmission, ion transport, epilepsy, behavioral abnormality, chemokinesis, histone deacetylation, and immunity." Epilepsy and autism is a recurrent theme in the research and clinical literature (see here for example) so there are no great surprise there. 'Immunity' and autism is something else that keeps cropping time and time and time again (see here).I appreciate that the authors also acknowledge that whilst autism was the focus on the current work, they do also mention: "By correlating histone acetylation with genotype, we discovered >2,000 histone acetylation quantitative trait loci (haQTLs) in human brain regions, including four candidate causal variants for psychiatric diseases." This opens up the idea that various different psychiatric/behavioural labels might show 'overlap' when it comes to the histone acetylome too.Interesting stuff by all accounts. I do like the idea that autism research is continuing to look at other areas of gene expression outside of just structural issues to the genome being linked to the condition (or should that be plural). Aside from the fact that people don't walk around with their genes permanently stuck in the 'on or off position' in every tissue all the time, the whole epigenetics field is a welcome complement to more traditional genomics. The focus on gene expression being potentially 'modifiable' might also reunite genetics and environment too (see here).Criticisms of the Sun study? Well, brain samples from the deceased are a precious resource but not without complications when it comes their use for science (see here). I appreciate that we don't have the technology to look at histone acetylation in real-time or real-life yet with the brain in mind but one has to be cautious about the results from the brains of the deceased who may have passed away for many different reasons. There is also the temptation to move the whole epigenetics 'thing' towards acetylation on the basis of such research, but the methylome still remains potentially important (see here) and probably for more than one reason (see here). Perhaps soon we'll see a study looking at more than one epigenetic factor with autism in mind?Going back to the concept of 'environmental influences' mentioned in the Sun paper, there are some potentially important repercussions from study results such as these. As with the concept of DNA methylation, one of the important concepts linked to the science of epigenetics is that such chemical alterations affecting the expression of DNA are potentially modifiable. This could mean that particular environmental factors working at critical periods might affect acetylation and methylation patterns and onward the expression of certain genes pertinent to the presentation of something like autism or at least facets of autism. The other scenario is that certain 'conditions' or 'interventions' might 'reverse such changes. On that last point, I might bring in some previous discussions on this blog in relation to something called HDAC (histone deacetylase) inhibitors (see here) that, as their name suggests, have the ability to inhibit the action of histone deacetylases (they remove acetyl groups). Various classes of medicines are classed at HDAC inhibitors including something called valproic acid which has some autism research history (see here for example). It's not therefore beyond the realms of possibility that the actions of certain medicines or other non-genetic factors with an influence on acetylation could be a source for further research in this area.Independent replication is the next stage... Read more »
Sun, W., Poschmann, J., Cruz-Herrera del Rosario, R., Parikshak, N., Hajan, H., Kumar, V., Ramasamy, R., Belgard, T., Elanggovan, B., Wong, C.... (2016) Histone Acetylome-wide Association Study of Autism Spectrum Disorder. Cell, 167(5), 1385-2147483647. DOI: 10.1016/j.cell.2016.10.031
Last week I returned from the 6th annual IMO Workshop at the Moffitt Cancer Center in Tampa, Florida. As I’ve sketched in an earlier post, my team worked on understanding ruxolitinib resistance in chronic myelomonocytic leukemia (CMML). We developed a suite of integrated multi-scale models for uncovering how resistance arises in CMML with no apparent […]... Read more »
Merlevede, J., Droin, N., Qin, T., Meldi, K., Yoshida, K., Morabito, M., Chautard, E., Auboeuf, D., Fenaux, P., Braun, T.... (2016) Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents. Nature Communications, 10767. PMID: 26908133
In the forests of West Africa, bands of handsome primates called Diana monkeys roam the tree branches. Each group has just one male and several females with their babies. The tradeoff for his apparently cushy living situation is that the male has to chase off predators. His female companions use specific calls to tell him what kinds of threats are nearby. And he responds to whatever they tell him—even if it goes against his own judgment.
Diana monkeys (Cercopithecus diana) of both sex... Read more »
Stephan, C., & Zuberbühler, K. (2016) Persistent Females and Compliant Males Coordinate Alarm Calling in Diana Monkeys. Current Biology, 26(21), 2907-2912. DOI: 10.1016/j.cub.2016.08.033
Birt–Hogg–Dubé syndrome (BHD) is caused by germline mutations in the FLCN gene and characterized by fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal tumours. The stretch hypothesis for pulmonary cyst formation proposes that cysts in BHD arise from defects in cell–cell adhesion, leading to repeated respiration-induced physical stretch-induced stress and, over time, expansion of alveolar spaces particularly in vulnerable regions of lung (Kennedy et al., 2016). A new study by Hoshika et al. (2016) has shed some light on this mechanism. The authors isolated lung fibroblasts from BHD patients and evaluated them by testing chemotaxis to fibronectin and three-dimensional (3-D) gel contraction. They showed that FLCN is associated with chemotaxis in lung fibroblasts and that, together with reduced TGF-β1 expression by BHD lung fibroblasts, FLCN haploinsufficiency seems to cause lung fibroblast dysfunction, impairing tissue repair.... Read more »
Hoshika, Y., Takahashi, F., Togo, S., Hashimoto, M., Nara, T., Kobayashi, T., Nurwidya, F., Kataoka, H., Kurihara, M., Kobayashi, E.... (2016) Haploinsufficiency of the gene leads to impaired functions of lung fibroblasts in patients with Birt–Hogg–Dubé syndrome . Physiological Reports, 4(21). DOI: 10.14814/phy2.13025
by Piter Kehoma Boll A flatworm again, at last! Not a land planarian, but a flatworm nonetheless. If there is a group of flatworms that may put land planarians in second plan regarding beauty, those are the polyclads. Living in … Continue reading →... Read more »
"The overall CD [coeliac disease or celiac disease depending on where you live] prevalence was 2.62%, which is statistically significant higher to that reported in the Italian paediatric population... If replicated, these data suggest the importance of regular screening for CD in young patients with ASD [autism spectrum disorder]."Those were some of the findings/conclusions reported in the paper by Sara Calderoni and colleagues  (open-access) and with them, some important data quite pertinent to some of the primary interests of this blog and indeed, my research career.Coeliac disease is an autoimmune condition (NOT AN ALLERGY!) whereby genetics, biology and environment converge on how dietary gluten - the stuff in foods like bread, pasta and cereals - is not necessarily a great idea for everyone. The ideas that: (a) a diagnosis of autism or ASD is seemingly protective of nothing and (b) all that chatter about gluten potentially affecting 'some' autism  plays heavily into the quite longstanding research history probing any connection between CD and autism. The question of whether CD is over-represented in autism has had many twists and turns including famously being studied by a certain H Asperger charcter.Calderoni and colleagues, drawing on data from a country with more than it's fair share of interest in CD, retrospectively examined data for over 380 children diagnosed with an ASD who had also been screened (serologically) for possible CD. Such screening included "determination of the titres of Anti-Gliadin (AGA) immunoglobuline (Ig)A and IgG, Anti-Transglutaminase (anti-tTG) IgA, and Anti-Endomysium (EMA) IgA antibodies." Further examinations of medical records for those screening positive to some of these parameters was undertaken to see "whether the CD diagnosis had been subsequently confirmed by paediatric gastroenterologists."Results: ten participants were identified "with CD or with positive CD serology." The authors provide some details about these 10 children - "six males and four females, with mean age of 41 months." They make an important point about their 'prevalence of CD' figures: "the prevalence of “CD patients plus screening detected individuals with both anti-tTG and EMA positivity” was 2.62% (10/382 subjects)." This based on the fact that not everyone of these 10 children had formally received a diagnosis of CD from a gastroenterologist for various reasons. Interestingly too, when it came to the data about whether CD was symptomatic i.e. outside of just being serologically present whether the corresponding symptoms of CD were present, the authors conclude that quite a few "had no symptoms or risk factors correlated with CD at the time of the serological screening." Finally, compared with other population data on CD prevalence, researchers suggested that CD may be yet another over-represented comorbidity following a diagnosis of ASD.Interestingly, the authors suggest that their figures on CD in ASD might be an underestimate. They say this based on the idea that for example, generally low IgA levels is an issue when it comes to CD screening and onwards the possibility of false-negative results . Although not necessarily widespread, low levels of IgA or IgA deficiency is not an unstrange finding in relation to some 'types' of autism .I can't argue with the Calderoni findings and the potential importance of preferential screening for CD when a diagnosis of autism is received  . What I might add however, is that more and more science and clinical practice is understanding that there are grey areas between coeliac disease and not coeliac disease (see here) and such notions on 'non-coeliac gluten/wheat sensitivity' might open up issues with gluten for quite a few more people diagnosed on the autism spectrum (see here). Indeed, as I always seem to do when talking about such issues, I would refer you to my 'Gluten and autism: probably not coeliac disease but...' post (see here) as representing an important step in our understanding of this topic. That and the idea that birds of an autoimmune feather tend to flock together, and other potential associations are opened up as a result of any links between coeliac disease and autism (see here)...But whatever you do, don't mention leaky gut as potentially also being involved (see here) (whisper it instead).---------- Calderoni S. et al. Serological screening for Celiac Disease in 382 pre-schoolers with Autism Spectrum Disorder. Italian Journal of Pediatrics. 2016; 42: 98. Whiteley P. Nutritional management of (some) autism: a case for gluten- and casein-free diets? Proc Nutr Soc. 2015 Aug;74(3):202-7. Prince HE. et al. Immunoglobulin A (IgA) Deficiency and Alternative Celiac Disease-Associated Antibodies in Sera Submitted to a Reference Laboratory for Endomysial IgA Testing. Clinical and Diagnostic Laboratory Immunology. 2000;7(2):192-196. Wasilewska J. et al. Low serum IgA and increased expression of CD23 on B lymphocytes in peripheral blood in children with regressive autism aged 3-6 years old. Archives of Medical Science : AMS. 2012;8(2):324-331. Genuis SJ. & Bouchard TP. Celiac disease presenting as autism. J Child Neurol. 2010 Jan;25(1):114-9.----------Calderoni, S., Santocchi, E., Del Bianco, T., Brunori, E., Caponi, L., Paolicchi, A., Fulceri, F., Prosperi, M., Narzisi, A., Cosenza, A., Tancredi, R., & Muratori, F. (2016). Serological screening for Celiac Disease in 382 pre-schoolers with Autism Spectrum Disorder Italian Journal of Pediatrics, 42 (1) DOI: 10.1186/s13052-016-0308-x... Read more »
Calderoni, S., Santocchi, E., Del Bianco, T., Brunori, E., Caponi, L., Paolicchi, A., Fulceri, F., Prosperi, M., Narzisi, A., Cosenza, A.... (2016) Serological screening for Celiac Disease in 382 pre-schoolers with Autism Spectrum Disorder. Italian Journal of Pediatrics, 42(1). DOI: 10.1186/s13052-016-0308-x
"After adjustment for several confounders, longer duration of breastfeeding was independently associated with better cognitive development and with fewer autistic traits."So said the paper by Olivier Boucher and colleagues  communicating findings based on the examination of data from "the INMA Project, a Spanish multicenter birth-cohort study" (an initiative that has cropped up on this blog before).Including over 1300 children who were subject to a battery of psychometric and behavioural assessments, researchers set about examining how various scores might be 'associated' with breastfeeding patterns: "Duration of any, predominant, and exclusive breastfeeding." The results as I've mentioned, seemed to show something of a connection between breastfeeding and particularly when it came to 'autistic traits' as assessed by the Childhood Autism Spectrum Test (CAST). I'll leave readers to draw their own conclusions about the relevance of this finding. Insofar as the more general conclusion on breastfeeding potentially aiding offspring cognitive development, well, let's just say that this has previously been mentioned before in the research literature (see here).Having talked about breastfeeding in the context of autism before on this blog (see here) I don't really want to head too far into the collected literature in this area alongside the other aspects/discussions that it draws in. All I will say is that the relationship between breastfeeding patterns and offspring autism/autistic traits is not likely to be straight-forward  (few things with regards to autism research ever are) and there could even be occasions when breast milk might not be the preferred option* (see here) (*I should reiterate that I am not providing medical or clinical advice on this blog). There are, for example, a multitude of potentially confounding variables that could impact on any association between the two; not least that early manifestations of offspring autism might already be present and impacting on the ease of breastfeeding practices during the very earliest days and weeks of infancy. I'm not gonna say too much more on this topic at this time but will perhaps return to the subject in future posts.---------- Boucher O. et al. Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain. Pediatr Res. 2016 Nov 15. Penn AH. et al. Breast Milk Protects Against Gastrointestinal Symptoms in Infants at High Risk for Autism During Early Development. J Pediatr Gastroenterol Nutr. 2016 Feb;62(2):317-27.----------Boucher O, Julvez J, Guxens M, Arranz E, Ibarluzea J, Sánchez de Miguel M, Fernández-Somoano A, Tardon A, Rebagliato M, Garcia-Esteban R, O'Connor G, Ballester F, & Sunyer J (2016). Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain. Pediatric research PMID: 27846197... Read more »
Boucher O, Julvez J, Guxens M, Arranz E, Ibarluzea J, Sánchez de Miguel M, Fernández-Somoano A, Tardon A, Rebagliato M, Garcia-Esteban R.... (2016) Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain. Pediatric research. PMID: 27846197
Apolipoprotein A5 gene (APOA5) is one of the genes implicated in contributing to a predisposition for hypertriacylglycerolaemia (HTG), a complex polygenic pathology that is highly influenced by environment. Hypertriacylglycerolaemia is characterized by having high circulating triacylglycerol levels and is a significant risk factor for cardiovascular disease and atherosclerosis. This genetic predisposition has an inherited component (based on polymorphisms) as well as an acquired component regulated by the environment (epigenetic modifications). We hypothesized that the integrated analysis of both components will improve our capacity to estimate APOA5 gene contribution to HTG.
We followed a recruit-by-genotype strategy to study a population of individuals with high cardiovascular disease risk. We selected 44 carriers of at least one APOA5 SNP (-1131TC and/or, S19W and/or 724CG, all of them being previously associated with HTG) and compared them against 34 individuals wild-type for these SNPs. DNA methylation patterns of three APOA5 regions [promoter, exon 2 and CpG island (CGI) in exon 3] were evaluated using sodium bisulfite conversion followed by pyrosequencing. We also obtained information of plasma biochemical analysis and lipoprotein plasma profile distribution analysed by nuclear magnetic resonance using the LipoProfile-3 algorithm.... Read more »
Oliva, I., Guardiola, M., Vallve, J., Ibarretxe, D., Plana, N., Masana, L., Monk, D., & Ribalta, J. (2016) APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels. Clinical Science, 130(22), 2053-2059. DOI: 10.1042/CS20160433
"This study does not support the hypothesis that MPH [methylphenidate] increases risk of incident psychotic events. It does indicate an increased risk of psychotic events before the first prescription of MPH, which may be because of an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment."The results published by Man and colleagues  (open-access) sit right with me. I say that on the basis that previous research suggesting that attention-deficit hyperactivity disorder (ADHD) may 'prime' someone for an elevated risk of developing psychosis (see here) has potentially received some welcome substantiation. That MPH might not be the bogeyman that some people might think (see here too) is also an important part of the Man findings (minus any charges of me providing medical or clinical advice on this blog... I'm not).The Man paper is open-access but a few choice details are worthwhile mentioning:Based on data from the "Clinical Data Analysis and Reporting System (CDARS)" an initiative based in Hong Kong, researchers set about identifying those "aged 6–19 years who received at least one prescription of MPH with at least one psychotic disorder and/or hallucination diagnostic code (psychotic events) during the study period (January 2001 to December 2014)." Given that only MPH and atomoxetine are seemingly licensed in the Hong Kong for "the treatment of ADHD", the authors were able to focus specifically on MPH quite easily.Although over 20,000 patients were in receipt of MPH prescriptions, only data for 103 participants were used in the study as a result of that diagnosis of a psychotic/hallucinatory condition. Most were male and 76 out of the 103 participants had "a clinical ADHD diagnosis."Researchers looked at MPH treatment and those psychotic/hallucinatory events taking into the account timing and including "a 90-day pre-exposure period" representing a period before MPH use (see here).Results: "The primary analysis indicated no statistically significant association between MPH treatment and occurrence of incident psychotic events." But, when compared with baseline data, there did seem to be something to see during that pre-exposure period (before MPH) and incident psychotic event(s). Ergo, something other than MPH use seemed to be linked to the experience of psychosis and we therefore head back to the idea that ADHD as one reason for MPH use might have some quite profound implications for future mental health.There is still quite a bit more to do in this area as per more longitudinal research with greater participant numbers. I might also draw your attention to Table 2 of the Man paper (see here) examining other 'psychiatric comorbidities' when it came to those participants experiencing a psychotic episode. The list of potential correlates is interesting in light of other work (see here).Whilst MPH comes out of such research with more than a whiff of roses, it is perhaps important to understand that medicines, all medicines come with potential side-effects and that includes MPH. Nevertheless, the idea that the benefits of controlled use of MPH might trump the risk of serious psychiatric side-effects such as psychosis is something that needs to be said and with it, a realisation that treating/managing the signs and symptoms of ADHD early, might have more profound repercussions for those diagnosed...---------- Man KKC. et al. Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system. Translational Psychiatry. 2016; 6: e956.----------Man, K., Coghill, D., Chan, E., Lau, W., Hollis, C., Liddle, E., Banaschewski, T., McCarthy, S., Neubert, A., Sayal, K., Ip, P., & Wong, I. (2016). Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system Translational Psychiatry, 6 (11) DOI: 10.1038/tp.2016.216... Read more »
Man, K., Coghill, D., Chan, E., Lau, W., Hollis, C., Liddle, E., Banaschewski, T., McCarthy, S., Neubert, A., Sayal, K.... (2016) Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system. Translational Psychiatry, 6(11). DOI: 10.1038/tp.2016.216
Note: We are rebooting our “Life in the Lab” series, which features interviews of interns and visitors. This post is by our inaugural OMA Visiting Fellow Rosa Fernández García, who spent a month with us earlier this year. You can follow Rosa on Twitter at @Rosamygale. —Christophe
Please introduce yourself and your research interests.
I received my bachelor’s degree in Biology (major in Zoology) at Complutense University in Madrid, Spain. I got my master’s and PhD at the same university with a thesis about phylogeny and phylogeography of cosmopolitan earthworms. After that, I moved to the lab of Prof. Gonzalo Giribet at Harvard University where I was a postdoc during 3 years and a Research Associate for another year. In January 2017, I’ll move to Barcelona to work as a Research Fellow in the lab of Dr. Toni Gabaldón at the Center for Genomic Regulation.
My research addresses fundamental questions about evolution in invertebrates: in other words, I am fascinated by how, when and where biodiversity took its form, and why it is maintained. My main two animal groups of interest are terrestrial annelids (oligochaetes) and (pan)arthropods, particularly the earliest branching lineages and most scientifically neglected groups (chelicerates and myriapods).
How did biodiversity took its shape? Resolving the tree of life. Macroevolutionary patterns are generally what we see when we look at the large-scale history of life. It encompasses the grandest trends and transformations in evolution, such as the origin of bilateral animals or the radiation of arthropods. In order to understand how lineages are related to each other, I study macroevolutionary patterns in several groups of invertebrates through phylogenetics and phylogenomics. I currently lead a fruitful line of research dealing with phylogenomics of myriapods and chelicerates, having optimized protocols to sequence successfully single individuals of the rarest and smallest arthropods. We are getting closer to resolve the Arthropod Tree of Life!
Artist’s rendition of the Arthropod tree of life
When and where? I tried to understand the mode and tempo of animal diversification patterns through the integration of phylogeography, biogeography and paleogeography.
Why? Comparative transcriptomics and genomics is a very powerful tool to shed light on very interesting evolutionary questions, such as arthropod terrestrialization - one of my favorite new lines of research.
Why did you choose to apply to the OMA visiting fellowship programme?
Orthology inference is one of the key steps in phylogenomics. I had been using OMA for a few years and I wanted to learn how I could use it more efficiently in my ongoing projects.
What project did you work on during your visit?
My project focused on optimizing OMA runs for some big and challenging data sets that I was having problems with. Also, I was interested in learning how I could exploit hierarchical orthogroups for comparative genomics studies in arthropods.
Rosa and David Dylus at coffee break (photo by Arthur Dessimoz)
Was there any highlight or low point you’d like to share?
It was a great experience to be in the Dessimoz lab for a month. As a systematist with relatively limited bioinformatic background, it was absolutely great to exchange ideas with computer scientists interested in the same scientific problems but with a completely different perspective that mine. It was a very enriching experience.
Do you have any practical tip for future OMA visiting fellows?
One month was not enough for me, so try to stay longer if your project is ambitious. And ask Christophe to bring a Tête de Moine cheese in your last day, it’s delicious!
Editor’s note: If you are interested in the OMA visiting fellowship programme, consult this page.
Fernández R, Laumer CE, Vahtera V, Libro S, Kaluziak S, Sharma PP, Pérez-Porro AR, Edgecombe GD, & Giribet G (2014). Evaluating topological conflict in centipede phylogeny using transcriptomic data sets. Molecular biology and evolution, 31 (6), 1500-13 PMID: 24674821
Fernández, R., Hormiga, G., & Giribet, G. (2014). Phylogenomic Analysis of Spiders Reveals Nonmonophyly of Orb Weavers Current Biology, 24 (15), 1772-1777 DOI: 10.1016/j.cub.2014.06.035
Fernández R, & Giribet G (2015). Unnoticed in the tropics: phylogenomic resolution of the poorly known arachnid order Ricinulei (Arachnida). Royal Society open science, 2 (6) PMID: 26543583
Novo M, Fernández R, Andrade SC, Marchán DF, Cunha L, & Díaz Cosín DJ (2016). Phylogenomic analyses of a Mediterranean earthworm family (Annelida: Hormogastridae). Molecular phylogenetics and evolution, 94 (Pt B), 473-8 PMID: 26522608... Read more »
Fernández R, Laumer CE, Vahtera V, Libro S, Kaluziak S, Sharma PP, Pérez-Porro AR, Edgecombe GD, & Giribet G. (2014) Evaluating topological conflict in centipede phylogeny using transcriptomic data sets. Molecular biology and evolution, 31(6), 1500-13. PMID: 24674821
Fernández, R., Hormiga, G., & Giribet, G. (2014) Phylogenomic Analysis of Spiders Reveals Nonmonophyly of Orb Weavers. Current Biology, 24(15), 1772-1777. DOI: 10.1016/j.cub.2014.06.035
Fernández R, & Giribet G. (2015) Unnoticed in the tropics: phylogenomic resolution of the poorly known arachnid order Ricinulei (Arachnida). Royal Society open science, 2(6), 150065. PMID: 26543583
Novo M, Fernández R, Andrade SC, Marchán DF, Cunha L, & Díaz Cosín DJ. (2016) Phylogenomic analyses of a Mediterranean earthworm family (Annelida: Hormogastridae). Molecular phylogenetics and evolution, 94(Pt B), 473-8. PMID: 26522608
Fernández R, Edgecombe GD, & Giribet G. (2016) Exploring Phylogenetic Relationships within Myriapoda and the Effects of Matrix Composition and Occupancy on Phylogenomic Reconstruction. Systematic biology, 65(5), 871-89. PMID: 27162151
Sharma, P., Fernandez, R., Esposito, L., Gonzalez-Santillan, E., & Monod, L. (2015) Phylogenomic resolution of scorpions reveals multilevel discordance with morphological phylogenetic signal. Proceedings of the Royal Society B: Biological Sciences, 282(1804), 20142953-20142953. DOI: 10.1098/rspb.2014.2953
Rosa Fernandez, Prashant Sharma, Ana LM Tourinho, & Gonzalo Giribet. (2016) The Opiliones Tree of Life: shedding light on harvestmen relationships through transcriptomics. BioRxiv. DOI: 10.1101/077594
I'm gonna be fairly brief today and draw your attention to yet another systematic review and meta-analysis this time looking at how "probiotic supplementation can have a positive effect on mood and psychological symptoms such as depression and anxiety."  Probiotics by the way, include a variety of bacteria and related lifeforms that are thought to confer some health advantage.The review/re-analysis by Jennifer McKean and colleagues found 7 studies on this topic in the peer-reviewed research literature, that overall "showed that supplementation with probiotics resulted in a statistically significant improvement in psychological symptoms... compared with placebo." Personally, I wasn't surprised at these findings having covered a few bits of science on probiotics and psychology before on this blog (see here for example). Some recent discussions on how probiotics might be a possible 'stress-reliever' (see here) also add to this area.I know some people are still a little sceptical of the whole 'gut-brain' thing (i.e. what goes on in the gut might have the ability to influence what goes on the grey/pink matter floating in the skull) and all the associated 'hype' that has accompanied the new science around the gut microbiota including the use of probiotics. There is lots more to do in this area; also overlapping with how other interventions may more detrimentally affect the trillions of bacteria that call us home and onwards may have 'psychological consequences' too (see here).But it is getting rather more difficult not to think that there may be some important processes at work in these times of psychobiotics ...---------- McKean J. et al. Probiotics and Subclinical Psychological Symptoms in Healthy Participants: A Systematic Review and Meta-Analysis. J Altern Complement Med. 2016 Nov 14. Dinan TG. et al. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013 Nov 15;74(10):720-6.----------McKean J, Naug H, Nikbakht E, Amiet B, & Colson N (2016). Probiotics and Subclinical Psychological Symptoms in Healthy Participants: A Systematic Review and Meta-Analysis. Journal of alternative and complementary medicine (New York, N.Y.) PMID: 27841940... Read more »
McKean J, Naug H, Nikbakht E, Amiet B, & Colson N. (2016) Probiotics and Subclinical Psychological Symptoms in Healthy Participants: A Systematic Review and Meta-Analysis. Journal of alternative and complementary medicine (New York, N.Y.). PMID: 27841940
"CRP [C-reactive protein] concentrations are increased in bipolar disorder regardless of mood state, but are higher during mania than in depression and euthymia, suggesting an increased inflammatory burden in mania."So said the systematic review and meta-analysis published by Brisa Fernandes and colleagues  who surveyed the peer-reviewed literature on the topic of "measured serum and plasma CRP concentrations in adult patients with bipolar disorder (as defined by DSM-IV-TR) and healthy controls" and arrived at their conclusions based on an analysis of some 2000 people diagnosed with bipolar disorder (BD). CRP by the way, a member of the pentraxin family, is the molecule of choice when it comes to looking at response to inflammation. BD, previously known as manic depression, is a condition characterised by periods of depression and mania.Continuing an important theme in psychiatry - that the immune system or expression of the immune system whether in terms of genetics or biology, seems to show some important associations with behaviour (see here for example) - the Fernandes paper represents important work. Of course it's not the first time that CRP levels and bipolar disorder have been mentioned on this blog (see here) but the 'collecting' of results based on the use of systematic review and meta-analysis this time around strengthens the association between these variables.Where next I hear you ask? Well, the idea that CRP levels might be linked to cases of BD needs further research not least to ensure that certain over-represented medical comorbidity linked to BD are not an interfering variable when it comes to CRP levels (see here). The findings should also perhaps be seen in a larger context where CRP levels have been reported in other psychiatric / behavioural labels (see here). The non-specificity of CRP (i.e. not tied to just one label) also has implications for the idea that many different psychiatric / behavioural labels might show overlapping features (see here) for example.With no medical or clinical advice given or intended, there is also the intriguing idea that interventions targeting specific immune function findings may also have behavioural implications (see here for example). This alongside the idea that some medicines intended for the treatment or management of aspects of BD may already have some 'immune-modulating' actions (see here) potentially tied into their potential efficacy (or not). Again, further research is very much implied.---------- Fernandes BS. et al. C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry. 2016 Nov 9. pii: S2215-0366(16)30370-4.----------Fernandes BS, Steiner J, Molendijk ML, Dodd S, Nardin P, Gonçalves CA, Jacka F, Köhler CA, Karmakar C, Carvalho AF, & Berk M (2016). C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. The lancet. Psychiatry PMID: 27838212... Read more »
Fernandes BS, Steiner J, Molendijk ML, Dodd S, Nardin P, Gonçalves CA, Jacka F, Köhler CA, Karmakar C, Carvalho AF.... (2016) C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. The lancet. Psychiatry. PMID: 27838212
The results published by Robert Joseph and colleagues  provide some blogging fodder today, observing that as part of the ELGAN (Extremely Low Gestational Age Newborns) Research Study, gestational age might matter when it comes to offspring risk of autism spectrum disorder (ASD).Gestational age is a measure of how far along a pregnancy is but in the context of the Joseph study refers to premature birth or those "born at least 3 months early." Researchers included data for nearly 1000 children born extremely premature using a prospective (rather than retrospective) methodology who, at age 10, were "evaluated for ASD and ID [intellectual disability]." They also took into account various other 'pregnancy information' derived from both medical records and interviews with mums. This included instances of cervical-vaginal ‘infection’ among other things.The results: over 90% of their cohort were assessed for autism/ASD and ID. Rates of ASD alone (without ID) were 3.2%. Some 3.8% of participants screened positive for autism and ID and 8.5% of participants presented with ID but not autism. Whilst these autism (with or without ID) rates might seem high, I'm not actually convinced that they are 'significantly higher' than that suggested in modern times (see here). The authors also noted that: "The lowest gestational age category (23-24 weeks) was associated with increased risk of ASD+/ID+... and ASD+/ID-."Also: "Maternal report of presumed cervical-vaginal ‘infection’ during pregnancy was associated with increased risk of ASD+/ID+." The sorts of things included under the heading of cervical-vaginal infection were "bacterial infection (n = 4), bacterial vaginosis (n = 30), yeast infection (n = 62), mixed infection (n = 4) or other/unspecified infection (n=43; e.g., chlamydia, trichomonas or herpes, etc.)."I agree with the authors that "low gestational age is associated with increased risk for ASD" and this research does seem to tally with other studies on this topic (see here for example). The one caveat I do want to make however is that the absolute numbers of children diagnosed with autism (with or without ID) were quite low (27 and 32 children respectively out of a total of 840) and somewhat dwarfed in comparison to those presenting with ID without autism (71 children out of 840). Still, preferential screening for autism and ID might be implied from these results; assuming that is, that the screening instrument in question is up to the job .As to potential mechanisms of effect... well, it's rather difficult to pin any 'excess autism risk' to any one mechanism in light of the various factors that can accompany prematurity. Aside from the immaturity of various biological system associated with premature birth (including the brain), the obvious effect of a reduced birth weight is something to consider (see here). I am also interested in the idea that infection (using the term quite broadly) during pregnancy might also impact on offspring autism risk in light of other data (see here). Specific pathogens during pregnancy affecting offspring developmental risks have already made a mark on the peer-reviewed research literature (see here for example) and could provide a template for the processes pertinent to infection plus prematurity too.---------- Joseph RM. et al. Extremely low gestational age and very low birth weight for gestational age are risk factors for ASD in a large cohort study of 10-year-old children born at 23-27 weeks gestation. American Journal of Obstetrics and Gynecology. 2016. Aug 13. Kim SH. et al. Predictive Validity of the Modified Checklist for Autism in Toddlers (M-CHAT) Born Very Preterm. J Pediatr. 2016 Nov;178:101-107.e2.----------Joseph, R., Korzeniewski, S., Allred, E., O’Shea, T., Heeren, T., Frazier, J., Ware, J., Hirtz, D., Leviton, A., & Kuban, K. (2016). Extremely low gestational age and very low birth weight for gestational age are risk factors for ASD in a large cohort study of 10-year-old children born at 23-27 weeks gestation American Journal of Obstetrics and Gynecology DOI: 10.1016/j.ajog.2016.11.1009... Read more »
Joseph, R., Korzeniewski, S., Allred, E., O’Shea, T., Heeren, T., Frazier, J., Ware, J., Hirtz, D., Leviton, A., & Kuban, K. (2016) Extremely low gestational age and very low birth weight for gestational age are risk factors for ASD in a large cohort study of 10-year-old children born at 23-27 weeks gestation. American Journal of Obstetrics and Gynecology. DOI: 10.1016/j.ajog.2016.11.1009
I don’t mean to brag, but I’ve got irritable bowel syndrome, says a character of a sitcom.
Irritable bowel syndrome used to be a rare condition, but became a problem of epidemic proportions, until the disease "came out of the closet". Then Internet searches and doctor visits started to dwindle down and less than halved compared to earlier decades.
Is IBS no longer a problem? [...]... Read more »
Camilleri M, Oduyebo I, & Halawi H. (2016) Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions. American journal of physiology. Gastrointestinal and liver physiology, 311(5). PMID: 27609770
Lacy BE, Patel H, Guérin A, Dea K, Scopel JL, Alaghband R, Wu EQ, & Mody R. (2016) Variation in Care for Patients with Irritable Bowel Syndrome in the United States. PloS one, 11(4). PMID: 27116612
Dorn, S., & Meek, P. (2013) Su1024 Ambulatory Care for Irritable Bowel Syndrome in the United States, 1993-2010. Gastroenterology, 144(5). DOI: 10.1016/S0016-5085(13)61392-X
Lackner, J., Brasel, A., Quigley, B., Keefer, L., Krasner, S., Powell, C., Katz, L., & Sitrin, M. (2010) The ties that bind: perceived social support, stress, and IBS in severely affected patients. Neurogastroenterology , 22(8), 893-900. DOI: 10.1111/j.1365-2982.2010.01516.x
The Zoo Hypothesis Hello? Anybody out there in the starry skies? If there are extra-terrestrial civilizations, why haven’t we heard from them yet? The sheer magnitude of the universe with its billions upon billions of stars has led many to suggest that life must have arisen more than once in the cosmos. Some have gone […]... Read more »
de Magalhães, J. (2016) A direct communication proposal to test the Zoo Hypothesis. Space Policy. DOI: 10.1016/j.spacepol.2016.06.001
Follicular lymphoma is a B-cell lymphoma that remains incurable with conventional therapies. Ying et al. (2016) present a new study exploring the biological and genetic features of follicular lymphoma and identifying potential new therapeutic targets. The authors identified recurrent mutations in the mTOR regulator RRAGC, a small G-protein, in approximately 10% of follicular lymphoma cases. Mutations in RRAGC localized to one protein surface area surrounding the GTP/GDP–binding sites. In stable retrovirally transfected HEK293T cells, multiple RRAGC mutations showed higher mTOR activation. A similar phenotype was observed in lymphoma cell lines and in yeast. Mutated RRAGC proteins showed increased binding to RPTOR, a binding protein for RRAG heterodimers, and decreased interactions with FLCN , a known tumour suppressor that plays a role in mTOR signalling and the causative gene of BHD syndrome.... Read more »
Ying ZX, Jin M, Peterson LF, Bernard D, Saiya-Cork K, Yildiz M, Wang S, Kaminski MS, Chang AE, Klionsky DJ.... (2016) Recurrent Mutations in the MTOR Regulator RRAGC in Follicular Lymphoma. Clinical cancer research : an official journal of the American Association for Cancer Research, 22(21), 5383-5393. PMID: 27267853
Consider this short blog post an extension of some previous discussions (see here and see here) on a rather peculiar 'association' between urinary tract infections (UTIs) and psychosis. UTIs basically refer to an infection in any part of the urinary system (kidneys, bladder, etc) typically treated with antibiotics. Psychosis is a state that causes a person to perceive or interpret things around them in an atypical way, usually accompanied by delusions or hallucinations. For a while now research has been connecting these two conditions.The paper by Chelsea Carson and colleagues  further adds to the peer-reviewed literature in this area with the observation of: "an association between UTIs and children and adolescents with acute non-affective psychosis." Based on a "retrospective chart review of 227 subjects ages 10–18 who were hospitalized between 2005 and 2014 for an acute episode of DSM-IV non-affective psychosis" compared with those presenting with depression with and without psychotic features, researchers noted that a UTI was not an uncommon diagnosis (20%). Bearing in mind the lack of any asymptomatic control group, authors concluded that screening for [comorbid] UTI in those presenting with acute psychosis might be warranted.I can't disagree with these findings and conclusions. Combined with other work  looking at "an association between an increased prevalence of UTI and acute psychotic relapse" in those diagnosed with schizophrenia, the idea that infection or immunological response to infection might have behavioural as well as physiological outcomes gathers strength from such findings. We still don't know all the hows-and-whys of such an association outside of the idea that inflammatory mechanisms may be at work (see here) but further investigations are most definitely implied.---------- Carson CM. et al. Urinary tract infections in children and adolescents with acute psychosis. Schizophrenia Research. 2016. Nov 10. Miller BJ. et al. A prevalence study of urinary tract infections in acute relapse of schizophrenia. J Clin Psychiatry. 2013 Mar;74(3):271-7.----------Carson, C., Phillip, N., & Miller, B. (2016). Urinary tract infections in children and adolescents with acute psychosis Schizophrenia Research DOI: 10.1016/j.schres.2016.11.004... Read more »
Carson, C., Phillip, N., & Miller, B. (2016) Urinary tract infections in children and adolescents with acute psychosis. Schizophrenia Research. DOI: 10.1016/j.schres.2016.11.004
Do you write about peer-reviewed research in your blog? Use ResearchBlogging.org to make it easy for your readers — and others from around the world — to find your serious posts about academic research.
If you don't have a blog, you can still use our site to learn about fascinating developments in cutting-edge research from around the world.
Research Blogging is powered by SMG Technology.
To learn more, visit seedmediagroup.com.