the infection of both mice and non-human primates with various ZIKV strains including the original ZIKV MR766 strain as well as strains from Asia (ZIKV FSS13025), Oceania (ZIKV H/PF/2013) and the Americas (ZIKV Paraiba 2015) as well as the infection of human placenta explants (ZIKV MR766 and ZIKV Nica-1/-2 2016) suggest that ZIKV can cross the placenta probably by infecting maternal cytotrophoblast cells (CTB) and maternal decidual fibroblast cells combined with placental injury due to the release of inflammatory cytokines. In addition, it has been proposed that either maternal antibodies against ZIKV or the closely related DENV might promote the entry of ZIKV-IgG complexes into cells in a process known as “Antibody-dependent Enhancement (ADE)”. ADE has been implicated in the development of severe forms of DENV associated hemorrhagic fever (Dengue hemorrhagic fever, DHF, or Dengue Shock Syndrome, DSS) which is generally thought to be caused by cross-reactive but not cross protective antibodies in which the antibodies produced during the infection with one DENV serotype fail to neutralize viral particles of a different serotype but instead facilitate the entry of DENV into cells bearing the Fc receptor such as monocyte derived macrophages or monocyte derived dendritic cells. Here the role of neutralising and non-neutralising antibodies against ZIKV in ZIKV ADE of infection is discussed. ... Read more »
Huang X, Yue Y, Li D, Zhao Y, Qiu L, Chen J, Pan Y, Xi J, Wang X, Sun Q.... (2016) Antibody-dependent enhancement of dengue virus infection inhibits RLR-mediated Type-I IFN-independent signalling through upregulation of cellular autophagy. Scientific reports, 22303. PMID: 26923481
Nour AM, Li Y, Wolenski J, & Modis Y. (2013) Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses. PLoS pathogens, 9(9). PMID: 24039574
Panyasrivanit M, Greenwood MP, Murphy D, Isidoro C, Auewarakul P, & Smith DR. (2011) Induced autophagy reduces virus output in dengue infected monocytic cells. Virology, 418(1), 74-84. PMID: 21813150
Dai L, Song J, Lu X, Deng YQ, Musyoki AM, Cheng H, Zhang Y, Yuan Y, Song H, Haywood J.... (2016) Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody. Cell host , 19(5), 696-704. PMID: 27158114
Charles AS, & Christofferson RC. (2016) Utility of a Dengue-Derived Monoclonal Antibody to Enhance Zika Infection In Vitro. PLoS currents. PMID: 27660733
Dejnirattisai W, Supasa P, Wongwiwat W, Rouvinski A, Barba-Spaeth G, Duangchinda T, Sakuntabhai A, Cao-Lormeau VM, Malasit P, Rey FA.... (2016) Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus. Nature immunology, 17(9), 1102-8. PMID: 27339099
Chan JF, Yip CC, Tsang JO, Tee KM, Cai JP, Chik KK, Zhu Z, Chan CC, Choi GK, Sridhar S.... (2016) Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs. Emerging microbes . PMID: 27553173
Sapparapu G, Fernandez E, Kose N, Cao B, Fox JM, Bombardi RG, Zhao H, Nelson CA, Bryan AL, Barnes T.... (2016) Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice. Nature. PMID: 27819683
Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Wang C, Fang-Hoover J, Harris E, & Pereira L. (2016) Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission. Cell host , 20(2), 155-66. PMID: 27443522
It's been quite a week hasn't it? Indeed for quite a few people it's been a stressful few days so perhaps timely that I'm talking about the 'attenuation of stress' in today's post.Despite the relatively small sample size included in the paper by by AP Allen and colleagues  there is something rather tantalising about their results suggesting that in healthy volunteers "consumption of B. longum [Bifidobacterium longum 1714] 1714 is associated with reduced stress and improved memory."Tantalising because as well as further directing research attention towards the important relationship that is the gut-brain axis (see here for another example) the findings provide initial support for the concept of "psychobiotics—live microorganisms with a potential mental health benefit" set within a human (not mouse) context.The Allen paper (who incidentally is on Twitter) is open-access and has previously provided signs that it was to be published (see here). Here are a few choice details:Take 22 (male) volunteers aged between 18 and 40 years of age who fitted various inclusion/exclusion criteria including no "self-report habitually taking any probiotic products" and ask them to take B. longum 1714 for 4 weeks after giving them a placebo preparation containing just maltodextrin and magnesium stearate and no probiotic for 4 weeks. Deliver various physical, psychometric and self-report questionnaires/tests at various intervals covering things like the "Socially evaluated cold pressor procedure" (SECPT) and other measures and see how things pan out according to placebo/psychobiotic use and after "a 2-week post-probiotic follow-up."Results: well, as per the opening paragraph of this post, there did seem to be some effects to be had potentially associated with B. longum administration. So, when it came to that 'put your hand in cold water' test (SECPT), participants as a group lasted slightly longer in the cold water than on previous testing occasions. When researchers looked at salivary cortisol levels (a measure of psychological stress) following this acute stress test, they observed some potentially important differences between the initial (baseline) test, the period covering placebo use and the period covering the psychobiotic use. This accompanied some differences in reported state anxiety. Such acute stress findings were also complemented by some subtle but potentially important differences in self-reported daily stress levels (lower) following the period of psychobiotic use (something that "returned to a higher level during the 2-week follow-up period"). The authors also report on some findings associated with testing cognition across the various phases of the study but I'm gonna stay focused on the stress part of things for now before anyone moves towards describing B. longum 1714 as some sort of nootropic of choice just yet.Of course there is still much to do in this area before anyone gets too carried away with things (how about a few more blinded RCTs pitting placebo against psychobiotic?) but the results are interesting. You could argue that there may have been some influence of practice effects associated with some of the results given the short timescales but I'm gonna take the findings at face-value. More so when when set in the context of other microbial preparations also potentially dealing with certain types of stress under experimental conditions (see here for example).Mode of action? Well, the authors mention the 'vagus nerve' as potentially being important given the suggestion of a connection between the trillions of wee beasties that populate our gut (the gut microbiota) and brain function(s). The specifics however are yet to be decided upon; and it is also worth noting that as part of the probiotic formulation called VSL#3, B. longum 1714 might have some important 'bowel' effects as per other findings (see here) onwards to behaviour(s) and labels (see here). I'm also intrigued by the finding that post-probiotic there was a suggestion of a waning of some of the previously reported effects implying that far from probiotics being accepted and 'assimilated' into our collected gut microbiota, there may be mechanisms at work tied to going back to the status quo."Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects." Wise words before anyone makes a run on B. longum 1714 or any related preparations but this is an interesting piece of research. Given also the so-far relatively good safety profile of various probiotics, there is an important argument for experimentally testing such stress relief and/or cognition-aiding properties under a wide range of contexts.To close, we lost another one in 2016. There must be a helluva party going on upstairs...---------- Allen AP. et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational Psychiatry. 2016; 6: e939.----------Allen AP, Hutch W, Borre YE, Kennedy PJ, Temko A, Boylan G, Murphy E, Cryan JF, Dinan TG, & Clarke G (2016). Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational psychiatry, 6 (11) PMID: 27801892... Read more »
Allen AP, Hutch W, Borre YE, Kennedy PJ, Temko A, Boylan G, Murphy E, Cryan JF, Dinan TG, & Clarke G. (2016) Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational psychiatry, 6(11). PMID: 27801892
Renal cell carcinoma (RCC) is by far the most common type of kidney cancer and it can be caused by genetic conditions such as BHD (Randall et al., 2014). BHD patients can develop multiple kidney tumours. In most cases these tumours can be surgically removed. However, surgery and traditional chemotherapies can leave patients with reduced renal function and at risk of relapse. In addition, advanced or metastatic RCC is difficult to treat with surgery. Therefore, the development and improvement of molecular targeted drug treatments is becoming a very active field. The standard first-line treatment for RCC is an anti-angiogenic and anti-proliferative tyrosine kinase inhibitor (TKI) such as sunitinib or sorafenib. This blog summarises recent results from a clinical trial assessing a new RCC drug treatment and the initiation of a new study.... Read more »
Randall, J., Millard, F., & Kurzrock, R. (2014) Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art. Cancer and Metastasis Reviews, 33(4), 1109-1124. DOI: 10.1007/s10555-014-9533-1
by Piter Kehoma Boll Most of you likely know what diatoms are, microscopic algae with a silica shell that are very abundant in the world’s oceans and one of the main oxygen producers. You may have seen images like the … Continue reading →... Read more »
Ianora, A., Poulet, S., Miralto, A., & Grottoli, R. (1996) The diatom Thalassiosira rotula affects reproductive success in the copepod Acartia clausi. Marine Biology, 125(2), 279-286. DOI: 10.1007/BF00346308
Krawiec, R. (1982) Autecology and clonal variability of the marine centric diatom Thalassiosira rotula (Bacillariophyceae) in response to light, temperature and salinity. Marine Biology, 69(1), 79-89. DOI: 10.1007/BF00396964
The important Doctor-Patient relationshipIn a slight departure from the typical material discussed on this blog, I want to briefly direct readers to the paper by (Prof) Paul Aveyard and colleagues  and results suggesting that: "A behaviourally-informed, very brief, physician-delivered opportunistic intervention is acceptable to patients and an effective way to reduce population mean weight."The title of this post comes from some of the media coverage of the Aveyard study summarising how general practitioners (GPs) in particular, might be ideally placed to bring up the topic of 'weight issues' when seeing some of their patients for other health matters.Minus any charges of plagiarism, I'd like to particularly draw readers attention to the example given in the Aveyard paper of a 'typical physician intervention'. So:"Physician: While you're here, I just wanted to talk about your weight. You know the best way to lose weight is to go to [Slimming World or Rosemary Conley] and that's available free on the NHS?Patient: Oh?Physician: Yes, and I can refer you now if you are willing to give that a try?Patient: Yes, ok.Physician: Ok, what you need to do is take this envelope back outside to the person who weighed you and they will book you into the weight loss course now.Patient: Ok.Physician: Good, but I'd like to see how you're getting on, so come and see me again in 4 weeks, please. Ok?Patient: Ok, see you then."In these days of the 10-minute consultation combined with something of an 'epidemic' of obesity and overweightedness I like the idea that a 30-second chat from an authority figure like a GP with a patient can potentially transform lives, even if only a proportion of the intended market. Despite the fact that only 40% of those offered weight reduction classes actually attended, there are some pretty decent statistics included in the paper to suggest that for this group, weight change was better than for those who weren't offered any additional support ("mean weight change at 12 months was 2·43 kg with the support intervention and 1·04 kg with the advice intervention, giving an adjusted difference of 1·43 kg"). And with decreasing weight, so the risk of various other health complaints also decreases accepting the old/new adage of 'not out-running a bad diet' .In these days of the soundbite and 140-characters or less, it makes me wonder what other health promotion advice might be amenable to a very brief chat from someone like a GP?To close, lest we forget...---------- Aveyard P. et al. Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial. Lancet. 2016. Oct 24. Malhotra A. et al. It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet. Br J Sports Med. 2015 Aug;49(15):967-8.----------Aveyard, P., Lewis, A., Tearne, S., Hood, K., Christian-Brown, A., Adab, P., Begh, R., Jolly, K., Daley, A., Farley, A., Lycett, D., Nickless, A., Yu, L., Retat, L., Webber, L., Pimpin, L., & Jebb, S. (2016). Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial The Lancet DOI: 10.1016/S0140-6736(16)31893-1... Read more »
Aveyard, P., Lewis, A., Tearne, S., Hood, K., Christian-Brown, A., Adab, P., Begh, R., Jolly, K., Daley, A., Farley, A.... (2016) Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial. The Lancet. DOI: 10.1016/S0140-6736(16)31893-1
Highlights of the month include a Special Issue on Blastocystis appearing in Parasitology International, a study of mitochondrial genomes, relationships between gut parasites and gut bacteria, and a announcement of an EMBO anaerobic protist conference next year in the UK.... Read more »
Dogruman-Al F, Stensvold CR, & Yoshikawa H. (2016) Editorial - PAR INT - special issue on Blastocystis. Parasitology international, 65(6 Pt B), 749. PMID: 27742000
Jacob AS, Andersen LO, Pavinski Bitar P, Richards VP, Shah S, Stanhope MJ, Stensvold CR, & Clark CG. (2016) Blastocystis mitochondrial genomes appear to show multiple independent gains and losses of start and stop codons. Genome biology and evolution. PMID: 27811175
Iebba V, Santangelo F, Totino V, Pantanella F, Monsia A, Di Cristanziano V, Di Cave D, Schippa S, Berrilli F, & D'Alfonso R. (2016) Gut microbiota related to Giardia duodenalis, Entamoeba spp. and Blastocystis hominis infections in humans from Côte d'Ivoire. Journal of infection in developing countries, 10(9), 1035-1041. PMID: 27694739
Smith DR. (2016) The past, present and future of mitochondrial genomics: have we sequenced enough mtDNAs?. Briefings in functional genomics, 15(1), 47-54. PMID: 26117139
In a year of impossible things...I was rather interested to read the recent paper by Renee Goodwin and colleagues  observing that: "Atopy appears to be associated with increased vulnerability to affective and anxiety problems, compared to youth without atopy."Atopy, referring to a predisposition to developing allergic diseases such as eczema, asthma and/or hayfever, is something on the 'up' in research terms when it comes to aspects of psychiatry and/or developmental outcomes (see here for example). Goodwin et al set about further testing the possibility of a link based on data "drawn from the Raine Study (N = 2868) [a favourite initiative on this blog], a population-based birth cohort study in Western Australia."Looking at signs of atopy - "using parent report and objective biological confirmation (sera IgE)" - at ages 1-5 years and "the range of internalizing and externalizing mental health problems at ages 5-17 years" authors reported on some interesting patterns/correlations in relation to affective and anxiety problems potentially being linked. Authors also described how their results held strong even "after adjusting for a range of potential confounders."Whilst there are always going to be issues associated with studies linking one or two variables across various years, the Goodwin paper represents yet another example of how further research resources need to be ploughed into the area of immune function and behaviour. Yes, I appreciate that we are entering the era of immunopsychiatry (if I can call it that) and that there is some good science emerging in this area (see here) but questions about the [various] hows and whys still need answering .---------- Goodwin RD. et al. Childhood atopy and mental health: a prospective, longitudinal investigation. Psychol Med. 2016 Oct 20:1-9. Hatfield SJ. et al. What's new in atopic eczema? An analysis of systematic reviews published in 2014. Part 1. Epidemiology, risk factors and outcomes. Clin Exp Dermatol. 2016 Nov 2.----------Goodwin RD, Robinson M, Sly PD, & Holt PG (2016). Childhood atopy and mental health: a prospective, longitudinal investigation. Psychological medicine, 1-9 PMID: 27762174... Read more »
Goodwin RD, Robinson M, Sly PD, & Holt PG. (2016) Childhood atopy and mental health: a prospective, longitudinal investigation. Psychological medicine, 1-9. PMID: 27762174
I am weathering the US election in Tampa, Florida. For this week, I am back at the Moffitt Cancer Center to participate in the 6th annual IMO Workshop. The 2016 theme is one of the biggest challenges to current cancer treatment: therapy resistance. All five teams participating this year are comfortable with the evolutionary view […]... Read more »
Ball M, List AF, & Padron E. (2016) When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia. Blood. PMID: 27707735
"Many individuals with ASD [autism spectrum disorder] have a distinctive behavioral presentation that is recognizable within moments, a phenomenon we call "frank" ASD." So said the paper by Ashley de Marchena & Judith Miller  who carried out an "empirical study of frank ASD" and by the looks of my Twitter feed when I initially posted about this study, there are quite a few varied opinions about the concept of 'frank' autism.Although 'frank autism' makes up a significant portion of the chatter about the de Marchena/Miller paper, the authors do provide an alternative description using the term "classic autism" and how "there is no unitary "classic" presentation, and classic autism does not seem to correspond to level of functioning." On that basis, they set about surveying just over 150 clinicians involved in the diagnostic assessment of autism/ASD using a "13-item questionnaire about frank ASD" and report results on just how many people in their cohort were familiar with this term, how widespread they thought it might be as well as how it might be comprised.Results: "Ninety-seven percentage of respondents were familiar with the phenomenon. Respondents estimated that 40% of the ASD population has a frank presentation." The sorts of behaviours respondents thought were most frequently associated with frank autism were things like eye contact issues, the "presence of motor mannerisms, and atypical gait or posture" and communicative styles. Surprisingly: "respondents reported detecting frank features rapidly, with the majority forming their impressions within the first ten minutes of interaction or observation." Ten minutes, eh?"We discuss these findings within the context of diagnostic decision-making and behavioral phenotyping of ASD" said the authors, as some important insights into clinical decisions about autism assessments are potentially revealed in this paper.In line with the comments received about this paper on social media, there are a few things to note. First and foremost is the idea that clinicians might be pretty good at spotting [some] autism fairly quickly. I don't think this should surprise anyone given that autism is diagnosed by behaviour (and developmental history) and whilst nothing beats a comprehensive assessment, experienced clinicians are always going to have 'hunches' or mental tick-boxes based on their previous experiences of diagnosing autism (or not). I might add that one needs only read some of the literature behind the development of the ICF core sets for autism (which are due out in the not-so-distant-future) to see such expertise in action (see here).But... experts whilst being experts aren't always correct as we've seen on other occasions when it comes to experts and autism screening/diagnosing (see here). There is also the suspicion that bias could be creeping into clinical decision-making too which could potentially affect diagnostic rates for specific groups for example (see here). Indeed, with all the changes being applied to some of the diagnostic criteria for autism as per the introduction of DSM-5, one wonders how such 'bias' is going to affect groupings such as the SCD 'catch-all' description (see here) for example?I would also be a little concerned that behaviours "absent from diagnostic criteria (e.g., atypical gait or posture)" are being potentially used to form clinical opinions/decisions. Yes, I appreciate that motor issues - potentially linked to gait and posture - are in the ascendancy again when it comes to autism (see here for example) but in light of known comorbidity accompanying autism such as dyspraxia for example  I think we have to be quite cautious about the mindset being applied here and how comorbidity is potentially being grouped into core autism. I might also add that the growing interesting in tic disorder(s) being 'over-represented' in autism is something else that could potentially be affected by such 'frank' thinking (see here).I'm a great believer in appropriate screening and detailed diagnostic assessment when it comes to autism on the basis of many variables, not least that autism rarely comes as a stand-alone diagnosis (see here) and that autistic traits are seemingly present across various other different labels too (see here and see here). Whilst it is not unexpected that those assessing and diagnosing day-after-day may build up a mental picture of what autism is (and isn't), there are cautions attached to the idea that clinical impressions are being formed seemingly so early during 'interaction or observation' and what this could mean for the heterogeneity of autism and the presentation of its important over-represented comorbidities.Music to close and something a little relaxed to ease your 2016 worries: Erik Satie - Gymnopédie No.1.---------- de Marchena A. & Miller J. "Frank" presentations as a novel research construct and element of diagnostic decision-making in autism spectrum disorder. Autism Res. 2016 Oct 21. MacNeil LK. & Mostofsky SH. Specificity of dyspraxia in children with autism. Neuropsychology. 2012 Mar;26(2):165-71.----------de Marchena, A., & Miller, J. (2016). “Frank” presentations as a novel research construct and element of diagnostic decision-making in autism spectrum disorder Autism Research DOI: 10.1002/aur.1706... Read more »
de Marchena, A., & Miller, J. (2016) “Frank” presentations as a novel research construct and element of diagnostic decision-making in autism spectrum disorder. Autism Research. DOI: 10.1002/aur.1706
Do you find gruyère gross? Are you repelled by roquefort?
Neuroscientists are now investigating why this might be. A new paper claims to reveal The Neural Bases of Disgust for Cheese.
French (heh) researchers Jean-Pierre Royet and colleagues used fMRI to scan 15 people who liked cheese and 15 who "hated" it. During the scan, the participants were shown images of cheese and were exposed to cheese odors.
The six neuro-cheeses were blue cheese, cheddar, goat cheese, gruyère, parmesan, ... Read more »
Royet JP, Meunier D, Torquet N, Mouly AM, & Jiang T. (2016) The Neural Bases of Disgust for Cheese: An fMRI Study. Frontiers in human neuroscience, 511. PMID: 27799903
Contrary to Murphy's Law - 'never repeat a successful experiment' - replication or reproducibility is a cornerstone of good science. Today, I'm blogging about a piece of research that aimed to do just that as per the findings reported by Stephen Walker and colleagues  (open-access).The title of this post has been borrowed from the title of the Walker paper to illustrate how moving on from the quite widely known 'fact' that functional gastrointestinal (GI) symptoms are over-represented when it comes to the label of autism (see here for example) so further research focus is required on more pathological bowel conditions potentially linked to autism too (see here). Yes, I know this potentially takes us into some uncomfortable territory but for those with autism suffering with various bowel issues (and I do mean suffering) this marks some important science for them and their families onward to the resolution of any further health inequalities.The latest Walker paper follows on from their original findings  which have been previously covered on this blog (see here) observing that: "ASDGI children have a gastrointestinal mucosal molecular profile that overlaps significantly with known inflammatory bowel disease (IBD), yet has distinctive features that further supports the presence of an ASD-associated IBD variant, or, alternatively, a prodromal phase of typical inflammatory bowel disease." ASDGI by the way, referred to their small grouping of "twenty five consecutive ASDGI cases (6 autism; 19 autism spectrum disorder) with histopathologic findings of ileitis, colitis, or both."This latest time around authors report on the extending of their 'initial findings' in "an additional case/control cohort." Further they "report a gene expression profile in peripheral blood that may reflect the presence of ASD-associated ileocolitis and provide a putative surrogate biomarker that, upon validation, would be of significant clinical relevance." Potentially, big words.The paper is open-access but here are a few choice details:Biopsy samples - "a specimen from each of seven anatomic locations (from the terminal ileum to rectum)" - and blood samples were provided by 21 participants (patients) diagnosed with an autism spectrum disorder (ASD). All presented with gastrointestinal (GI) symptoms and all had "a history of normal development for at least 12 months followed by developmental regression and onset of gastrointestinal symptoms." All also had "histologically-confirmed ileitis, colitis, or both in at least one of seven collected and archived colonic biopsies." A control group of 21 'typically-developing' children "without ASD who had gastrointestinal symptoms... but no identifiable histologic inflammation on any biopsies in either the ileum or colon" were also included for analysis.Part 1 of the study "compared whole genome gene expression profiles of inflamed ASD GI mucosal tissue (ASDIC+) to non-inflamed TD mucosal tissue (TDIC−) in biopsies from both the terminal ileum and colon." This is pretty much what was done by the authors during their first research voyage in this area. Part 2 was more novel insofar as blood gene expression profiles were compared between the groups. It's also important to note that: "blood was obtained from the same patients, and at the same time, as their respective mucosal tissue samples."Results: applying a statistical technique called Principal Component Analysis (PCA) looking at gene expression in those mucosal (bowel) samples, authors were again able to say that there were differences between inflamed and non-inflamed samples/groups. They also observed some potentially important differences in those blood samples too: "Nine of these DETs [gene transcripts that are differentially-expressed] were also differentially expressed in blood in our most recent cohort." You might ask what does this actually tell us about the autism+GI group? Well, nothing and something, insofar as it is not really being ethical to start taking bowel biopsies from children with autism without any indication to do so, which means that comparisons between non-GI and GI+ children with autism were not possible. The data do however suggest that a "putative peripheral marker could provide a proxy for gastrointestinal inflammation and also provide functional insights."Insofar as the details of what genes were being differentially expressed in ASDIC+ vs. TDIC- samples and how these overlapped with the previous study from the authors, there were some interesting candidates including "a key mitochondrial folate pathway gene, MTHFD2 (methylenetetrahydrofolate dehydrogenase (NADP + dependent) 2, methenyltetrahydrofolate cyclohydrolase)" hinting at an effect beyond just immune function and inflammation/inflammatory signalling. Authors modelled various combinations of these genes expressed (or not) to try and come up with some preliminary Receiver Operating Characteristic (ROC) curve analysis. Regular readers of this blog will probably have heard me talk about ROC analyses before (see here for example) with regards to the search for potential classifiers or biomarker profiles associated with autism. Bearing in mind the small participant numbers included in this study and the final figures arrived at, I'd suggest that quite a bit more work is required before anyone takes the reported findings as gospel just yet. But they are interesting...So, there you have it. This is important work for two reasons: (i) more pathological bowel states can and do present alongside autism  (the diagnosis of autism is seemingly protective of very little as science is learning) and (ii) with the strong requirement for further investigations in this area, science is seemingly starting on a path to potentially identifying blood-based 'biomarkers' possibly useful in identifying those who might benefit from further screening for such bowel issues.Given the history and debate in the area of bowel disease accompanying some autism, I'm not expecting giant fanfares to greet these results nor any big rush to try and prove/disprove these latest findings. That is an unfortunate truth and in the end, it is the children/adults with autism and significant GI issues who lose out as a consequence. The fact that this and the previous work by the authors is peer-reviewed science and not just speculation however will I think eventually be important, as talk about medical comorbidity accompanying autism continues at a pace  (see here too) and further moves towards 'what can we do about such issues?' eventually start to come to the forefront.And just before I go, there may also be other research uses for biopsies as and when they have to be taken from children/adults under clinical investigation ...To close, I note there is an election across the Pond. With all the nastiness that has followed the campaign, surely there's an easier way to pick the Leader of the Free World...---------- Walker SJ. et al. A Putative Blood-Based Biomarker for Autism Spectrum Disorder-Associated Ileocolitis. Sc... Read more »
Walker SJ, Beavers DP, Fortunato J, & Krigsman A. (2016) A Putative Blood-Based Biomarker for Autism Spectrum Disorder-Associated Ileocolitis. Scientific reports, 35820. PMID: 27767057
Superman donned glasses to disguise himself and blend in with other people. One snake hides its identity using a similar trick: when threatened, it changes the shape of its pupils. This makes it resemble a much more dangerous animal.
The mock viper (Psammodynastes pulverulentus) is mild-mannered, not superpowered. It's common across much of Asia, and—as you might have guessed from its name—looks a lot like a viper. Actual vipers are a widespread family of venomous snakes. Like true vipers... Read more »
Silva, I., Crane, M., Artchawakom, T., Suwanwaree, P., & Strine, C. (2016) More than meets the eye: change in pupil shape by a mock viper. Frontiers in Ecology and the Environment, 14(8), 453-454. DOI: 10.1002/fee.1420
In humans, the most common infectious neuroteratogenic agents are summarised by the mnemonic “TORCH(S)” (Toxoplasmosis, Others, Rubella, (Human) Cytomegalovirus, Herpes Simplex, Syphilis) with ZIKV either classified as “Others” or by expanding the mnemonic to TORCHSZ and indeed health authorities in affected countries regularly test cases of microcephaly suspected to be associated with neurological infections not only for ZIKV but also for the presence of TORCH(S). Microcephaly however is only one outcome of CNS defects that are associated with the infection of foetal neural cells with infectious agents, as illustrated by the wide range of symptoms of neonate that include hydrocephalus, cerebellar dysplasia, hypomyelinogenesis or microphthalmia.
Common to all pathogens is, that they infect the foetus in utero rather than intra partum or vertical by breastfeeding, suggesting that the infection of neural precursor or mature neurons during the development of the foetal brain causes abnormal foetal brain development. Therefore, it is crucial to examine both the ability of neuroteratogenic viruses to infect and replicate in vaginal tissue as well to examine the mechanism of transplacental transmission and thus infection of embryonic and/or foetal cells. Here the mechanism of foetal ZIKV infection via the maternal placenta is discussed. ... Read more »
Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL, Stutz B, Szigeti-Buck K, Van den Pol A, Lindenbach BD, Horvath TL.... (2016) Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection. Cell, 166(5), 1247-12560000. PMID: 27565347
Bayless NL, Greenberg RS, Swigut T, Wysocka J, & Blish CA. (2016) Zika Virus Infection Induces Cranial Neural Crest Cells to Produce Cytokines at Levels Detrimental for Neurogenesis. Cell host , 20(4), 423-428. PMID: 27693308
El Costa H, Gouilly J, Mansuy JM, Chen Q, Levy C, Cartron G, Veas F, Al-Daccak R, Izopet J, & Jabrane-Ferrat N. (2016) ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy. Scientific reports, 35296. PMID: 27759009
Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Wang C, Fang-Hoover J, Harris E, & Pereira L. (2016) Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission. Cell host , 20(2), 155-66. PMID: 27443522
Quicke KM, Bowen JR, Johnson EL, McDonald CE, Ma H, O'Neal JT, Rajakumar A, Wrammert J, Rimawi BH, Pulendran B.... (2016) Zika Virus Infects Human Placental Macrophages. Cell host , 20(1), 83-90. PMID: 27247001
Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S, Marques ET Jr, Cherry S, Sadovsky Y, & Coyne CB. (2016) Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection. Cell host , 19(5), 705-12. PMID: 27066743
Ning F, Liu H, & Lash GE. (2016) The Role of Decidual Macrophages During Normal and Pathological Pregnancy. American journal of reproductive immunology (New York, N.Y. : 1989), 75(3), 298-309. PMID: 26750089
Lash GE, Pitman H, Morgan HL, Innes BA, Agwu CN, & Bulmer JN. (2016) Decidual macrophages: key regulators of vascular remodeling in human pregnancy. Journal of leukocyte biology, 100(2), 315-25. PMID: 26819320
Salamonsen LA, Hannan NJ, & Dimitriadis E. (2007) Cytokines and chemokines during human embryo implantation: roles in implantation and early placentation. Seminars in reproductive medicine, 25(6), 437-44. PMID: 17960528
Olagnier D, Amatore D, Castiello L, Ferrari M, Palermo E, Diamond MS, Palamara AT, & Hiscott J. (2016) Dengue Virus Immunopathogenesis: Lessons Applicable to the Emergence of Zika Virus. Journal of molecular biology, 428(17), 3429-48. PMID: 27130436
"Epilepsy was reported to co-occur in 8.6 % of ASD [autism spectrum disorder] cases."That was the headline conclusion reported by Shiny Thomas and colleagues  as they drew on data from "the most recent U.S. National Survey of Children's Health, 2011-2012" to add to the extensive literature looking at how common epilepsy is when it comes to autism.Including some 1600 children/young adults diagnosed with autism - equivalent to a prevalence of 1.8% of the entire 85,000-strong cohort - researchers "examined parent-reported prevalence of co-occurring epilepsy" and eventually came up with that 8-9% figure. Further, they also observed that: "the co-occurrence of epilepsy was associated with increasing child age, female gender, intellectual disability, speech problems and lower socioeconomic status."This is important work. Epilepsy or seizure disorder is not something to be taken lightly under any circumstances; more so when applied to autism and the 'burden' of medical comorbidity that seems to be over-represented following a diagnosis (see here). The use of the U.S. National Survey of Children's Health (NSCH), 2011-2012 also has some significant strengths in terms of numbers of participants and has previously informed quite a few areas of autism research (see here for example).There is another important detail attached to the Thomas paper that is also worthy of comment in relation to how their prevalence figure compares with other independent studies in terms of epilepsy appearing comorbid to autism (readers should click on the 'Supplementary material' attachment shown here). Bearing in mind their data was derived from children "ages 2-17" and includes the term 'parent-reported' (as opposed to medical records reported) the 8.6% figure seems to be quite a conservative one. I say this on the basis that previous data from NSCH has observed slightly higher rates of epilepsy (see here) and other data sources have even talked about 1 in 5 children on the autism spectrum manifesting with a seizure or seizure disorder (see here). I of course realise that the word 'epilepsy' covers quite a bit of diagnostic ground and seizures/seizure disorder can present for a variety of reasons, but nonetheless I stand by the 8.6% comorbidity figure as perhaps being one of the lower values published in the peer-review domain.The additional observations that 'increasing age' and presence of intellectual (learning) disability might influence the presence of epilepsy in relation to autism are interesting but by no means novel findings. They do however offer something of a roadmap to monitoring those on the autism spectrum who may be at some enhanced risk of developing epilepsy and indeed, implementing the relevant strategies in a timely fashion to ensure that epilepsy is managed safely.Many questions still remain concerning the hows and whys of epilepsy intersecting with autism (and indeed, autism intersecting with epilepsy) including those related to more 'non-traditional' aspects (see here for example). What however is abundantly clear from the peer-reviewed and other literature in this area is that epilepsy is an important part of life for quite a few people on the autism spectrum and as many resources as possible should be pumped into looking at the relationship and offsetting / averting the potentially life-changing consequences that epilepsy can have on a person and their loved ones (see here).To close, when one mentions 'God Save the Queen' one should really specify which version one requires?---------- Thomas S. et al. Brief Report: Prevalence of Co-occurring Epilepsy and Autism Spectrum Disorder: The U.S. National Survey of Children's Health 2011-2012. J Autism Dev Disord. 2016 Oct 17.----------Thomas S, Hovinga ME, Rai D, & Lee BK (2016). Brief Report: Prevalence of Co-occurring Epilepsy and Autism Spectrum Disorder: The U.S. National Survey of Children's Health 2011-2012. Journal of autism and developmental disorders PMID: 27752862... Read more »
Thomas S, Hovinga ME, Rai D, & Lee BK. (2016) Brief Report: Prevalence of Co-occurring Epilepsy and Autism Spectrum Disorder: The U.S. National Survey of Children's Health 2011-2012. Journal of autism and developmental disorders. PMID: 27752862
by Piter Kehoma Boll This information was known by me and some other people for quite a while, but only recently has caught attention of the general public. Obama is the newest threat in Europe. No, I’m not talking about the … Continue reading →... Read more »
Álvarez-Presas, M., Mateos, E., Tudó, À., Jones, H., & Riutort, M. (2014) Diversity of introduced terrestrial flatworms in the Iberian Peninsula: a cautionary tale. PeerJ. DOI: 10.7717/peerj.430
Boll, P., & Leal-Zanchet, A. (2016) Preference for different prey allows the coexistence of several land planarians in areas of the Atlantic Forest. Zoology, 119(3), 162-168. DOI: 10.1016/j.zool.2016.04.002
Carbayo, F., Álvarez-Presas, M., Jones, H., & Riutort, M. (2016) The true identity of Obama (Platyhelminthes: Geoplanidae) flatworm spreading across Europe. Zoological Journal of the Linnean Society, 177(1), 5-28. DOI: 10.1111/zoj.12358
"This is the first study to identify the existence of sensory subtypes among older children and adolescents with ASD [autism spectrum disorder] and explore their association with anxiety levels."Far be it from me to question the above quote provided in the paper by Mirko Uljarević and colleagues  but I'm inclined to suggest that there has already been some research published on the link between sensory issues and anxiety in the context of the autism spectrum before (see here and see here). Indeed, I do wonder whether the assertions put forward by Mazurek and colleagues  on how gastrointestinal (GI) issues (yes, they are over-represented) might be an important part of any sensory/anxiety mix in autism could be something that is further looked at by Uljarević in their cohort?Anyhow, the Uljarević paper is an interesting one given the idea that within the vast heterogeneity that is autism (or even the autisms) sensory issues as measured by "the short sensory profile" are notuniform in their presentation (a shocker, I know). The finding that anxiety scores, as measured by the Spence anxiety scales, were potentially a little different according to sensory subtype (sensory adaptive, sensory moderate, sensory severe) particularly when it came to the sensory adaptive grouping - "Children and adolescents from the adaptive subtype had significantly lower anxiety scores when compared with other two subtypes" - is important. The implication being that with various other variables not differing (chronological age, expressive language, or severity of autism diagnostic features) sensory issues might be one important driver of the presentation of anxiety when it comes to autism.As I've mentioned quite a few times on this blog, the topic of anxiety and autism is an important one (see here for example). There are a few different 'types' of anxiety (or anxiety diagnoses) that might be more applicable to autism alongside some discussion about how to measure anxiety when it comes to autism (see here). But the primary messages are: (i) anxiety is pretty rife in terms of accompanying a diagnosis of autism and (ii) the effects of anxiety can be absolutely, utterly disabling. Set in this light, if there are things that can be done to overcome anxiety over and above what might be traditionally offered (see here) by for example, 'affecting' those sensory issues, many people potentially stand to benefit.Next question: how does one go about 'intervening' when sensory issues are present alongside autism? Well, the science is still a little sparse here outside of the odd case report on something like bumetanide showing a potential effect  for example. I might draw your attention to some preliminary work on how visual sensory issues might be a target for other interventions (see here) but there is still some way to go in that area too and one needs to be mindful of how ophthalmologic disorder(s) may also contribute (see here). Going back to the Mazurek paper and the 'triad' of sensory issues, anxiety and bowel problems hinted at with at least some autism in mind, one could speculate that treating said bowel issues *might* have further positive effects on sensory and anxiety issues too. Indeed, in the more general context of how anxiety and another important label - depression - may well have a functional bowel issue link (see here), there is plenty of research fodder to draw on hinting at a 'gut-brain' link in some cases. No doubt there are other ways and means to tackle sensory issues as and when they impact on quality of life and by the sounds of other research  sensory issues in autism as described by the DSM-5 are going to be pretty widespread.To close, it's 'Remember, remember the 5th of November, gunpowder, treason and plot..' day here in the UK today. So here's V and his revolutionary chatter again and please, be careful this Bonfire night.---------- Uljarević M. et al. Sensory subtypes and anxiety in older children and adolescents with autism spectrum disorder. Autism Res. 2016 Oct;9(10):1073-1078. Mazurek MO. et al. Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders. J Abnorm Child Psychol. 2013 Jan;41(1):165-76. Grandgeorge M. et al. The effect of bumetanide treatment on the sensory behaviours of a young girl with Asperger syndrome. BMJ Case Rep. 2014 Jan 31;2014. pii: bcr2013202092 Green D. et al. Brief Report: DSM-5 Sensory Behaviours in Children With and Without an Autism Spectrum Disorder. J Autism Dev Disord. 2016 Nov;46(11):3597-3606.----------Uljarević M, Lane A, Kelly A, & Leekam S (2016). Sensory subtypes and anxiety in older children and adolescents with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research, 9 (10), 1073-1078 PMID: 26765165... Read more »
Uljarević M, Lane A, Kelly A, & Leekam S. (2016) Sensory subtypes and anxiety in older children and adolescents with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research, 9(10), 1073-1078. PMID: 26765165
Furuya et al. (2016) present a new study describing genetic, epidemiologic and clinicopathologic features of 312 Asian individuals with BHD manifestations based on data from 120 probands from different families (119 Japanese and 1 Taiwanese), 36 siblingss with genetic testing and 156 siblings without genetic testing.... Read more »
Furuya M, Yao M, Tanaka R, Nagashima Y, Kuroda N, Hasumi H, Baba M, Matsushima J, Nomura F, & Nakatani Y. (2016) Genetic, epidemiologic and clinicopathologic studies of Japanese Asian patients with Birt-Hogg-Dubé syndrome. Clinical genetics, 90(5), 403-412. PMID: 27220747
by Piter Kehoma Boll Found throughout most of the world, you probably have encountered this fellow many times in your life, but did not pay any attention. After all, it is just a moss! Scientifically known as Bryum argenteum and popularly … Continue reading →... Read more »
Shaw, A., & Albright, D. (1990) Potential for the Evolution of Heavy Metal Tolerance in Bryum argenteum, a Moss. II. Generalized Tolerances among Diverse Populations. The Bryologist, 93(2), 187. DOI: 10.2307/3243622
The findings reported by Naushad Shaik Mohammad and colleagues  provide some blogging fodder today and the suggestion of a link between some of the genetics of the folate pathway and the finding of elevated levels of homocysteine with [some] autism in mind.OK, from the start, the genetics of folate metabolism mentioned in the context of autism typically means reference to the quite well replicated finding of issues with the gene methylenetetrahydrofolate reductase (MTHFR) (see here for some background). This gene (product) serves an important purpose in relation to the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate; the latter helping to convert the amino acid homocysteine to methionine. Outside of the importance of methionine to the process of DNA methylation (yep, some of that epigenetics stuff that you keep hearing about), there is quite a body of literature emerging to suggest that elevated levels of homocysteine might also have some important health effects.For quite a few years now, a specific genetic issue with MTHFR - MTHFR C677T - has been reported in quite a few people on the autism spectrum (see here). This allied to other independent research suggesting that the downstream effects of issues with MTHFR linked to elevations in levels of homocysteine may not also be an uncommon finding (see here). Shaik Mohammad et al therefore set about looking at the relationship between genetic issues with MTHFR and hyperhomocysteinemia in the context of autism.They did this by use of an "artificial neural network (ANN) model" where data initially from "138 autistic and 138 nonautistic children" on various genetic issues linked to folate metabolism (including MTHFR) were used as potential "predictors of autism risk." We are also told that: "Meta-analyses were carried out on 1361 ASD children and 6591 nonautistic children to explore the association of MTHFR C677T and homocysteine with the risk for ASD [autism spectrum disorder]."Results: well, the model wasn't exactly brilliant at predicting the risk of autism (63.8% accuracy). The authors call this a 'moderate' finding but I'd probably suggest that their results are yet another very good example of how heterogeneous the autism spectrum actually is. The idea of not using the term 'autism' as a research starting point in this context (see here) also receives support. Perhaps of greater importance were their findings linked to homocysteine and autism and how: "Hyperhomocysteinemia was observed in autistic children" to a greater extent that controls. They did also confirm that the MTHFR C677T genetic polymorphism was linked to 'inflating homocysteine levels' alongside another genetic issue called MTRR A66G (methionine synthase reductase). This is not an unusual finding in the context of what is already known about MTRR and homocysteine. The MTRR bit potentially linked to autism is however, something that this research group have previously suggested to 'reduce the risk' of autism .In terms of what these results mean in the context of autism, there are a few possibilities. First, screening. Knowing what we now seem to know about MTHFR and homocysteine in relation to quite a lot of people with autism, I would have thought it would be good practice to screen genetics/biochemistry. Minus any scaremongering or sweeping generalisations, the observation that hyperhomocysteinemia 'may' have links to cardiovascular disease and other adverse states for example, also perhaps implies screening save any further charges of health inequality when it comes to the label of autism. Next management. Far from being a 'nothing can be done about it' state, there is some good evidence that small adjustments to nutrition can potentially have positive effects on some of these parameters. With no medical or clinical advice given or intended, high levels of homocysteine seem in some cases, to be reactive to certain vitamin supplementation. The focus on vitamin B12 could also be set in the context of other recent studies of this vitamin (and its vitamers) with autism in mind (see here) (but I am careful not to link the two parameters just yet). And just recently there is news that there is a new way of assaying for vitamin B12 on the horizon which could also be useful. Finally, more research is indicated. As per my discussions not so long ago about another potentially important link to folate metabolism and autism (see here), there does appear to be quite a bit more to see when it comes to the folate cycle intersecting with homocysteine metabolism (and it's downstream effects). Yes, we can talk about whether folate is 'protective' or not when it comes to 'risk' of autism (see here and see here) but what this latest work suggests is that this area is complicated and potentially includes many genetic/epigenetic/biochemical variables that need to be taken into account.---------- Shaik Mohammad N. et al. Clinical utility of folate pathway genetic polymorphisms in the diagnosis of autism spectrum disorders. Psychiatr Genet. 2016 Oct 17. Mohammad NS. et al. Aberrations in folate metabolic pathway and altered susceptibility to autism. Psychiatr Genet. 2009 Aug;19(4):171-6.----------Shaik Mohammad N, Sai Shruti P, Bharathi V, Krishna Prasad C, Hussain T, Alrokayan SA, Naik U, & Radha Rama Devi A (2016). Clinical utility of folate pathway genetic polymorphisms in the diagnosis of autism spectrum disorders. Psychiatric ge... Read more »
Shaik Mohammad N, Sai Shruti P, Bharathi V, Krishna Prasad C, Hussain T, Alrokayan SA, Naik U, & Radha Rama Devi A. (2016) Clinical utility of folate pathway genetic polymorphisms in the diagnosis of autism spectrum disorders. Psychiatric genetics. PMID: 27755291
A new paper could prompt a rethink of a basic tenet of neuroscience. It is widely believed that the motor cortex, a region of the cerebral cortex, is responsible for producing movements, by sending instructions to other brain regions and ultimately to the spinal cord. But according to neuroscientists Christian Laut Ebbesen and colleagues, the truth may be the opposite: the motor cortex may equally well suppress movements.
Ebbesen et al. studied the vibrissa motor cortex (VMC) of the rat, ... Read more »
Ebbesen CL, Doron G, Lenschow C, & Brecht M. (2016) Vibrissa motor cortex activity suppresses contralateral whisking behavior. Nature Neuroscience. PMID: 27798633
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