Whilst the package inserts of the various drugs that modern medicine has at its disposal provides important information on potential mode of action, there is a growing realisation that drugs generally have quite a few more molecular targets than are perhaps listed. Take for example the quite commonly used (in some parts of the world anyway) compound called melatonin that in some instances can provide almost miraculous relief when it comes to sleeping issues under certain circumstances. A derivative of the amino acid tryptophan, melatonin might however be quite the molecular handy-person when it comes to its biological targets including its actions on something called leaky gut for example...The paper by Lin Yuan and colleagues  similarly suggests that everyone's favourite 'cuddle hormone' (oxytocin) might also have a wider range of biological effects than has hitherto been fully appreciated. Drawing on cell line results and intra-nasal administration of oxytocin (OT) to [artificially] immune-stimulated mice, authors reported that "OT possesses anti-neuroinflammatory activity and might serve as a potential therapeutic agent for treating neuroinflammatory diseases."One of the primary analytical targets of the Yuan study were microglia, those 'constant gardeners' according to one description, and how administration of OT might have some interesting effects on the activation of microglia under certain circumstances. "BV-2 cells and primary microglia were pre-treated with OT (0.1, 1, and 10 μM) for 2 h followed by LPS [lipopolysaccharides] treatment" we are told, and microglia activation and "pro-inflammatory mediators" subsequently monitored. The results tallied with those 'anti-neuroinflammatory' sentiments previously expressed as authors report on various possible reasons for such an effect: "OT suppressed the expression of TNF-α, IL-1β, COX-2, and iNOS at the mRNA and proteins levels and reduced the elevation of [Ca2+]i in LPS-stimulated microglia cells." If that wasn't enough, researchers also looked at what happened following OT pre-treatment when a certain strain of mouse was 'immune stimulated' again in terms of microglia activation and those pro-inflammatory mediators. We are similarly told that: "pre-treatment with OT showed marked attenuation of microglial activation and pro-inflammatory factor levels." So we have something of a match in the lab and in an animal model.These are interesting results. Yet again, one has to be a little cautious about the use of mouse models or indeed, cell lines (humans are so much more than a group of cells in a petri dish) and further, independent investigations are indicated. But: "These data suggested that OT would be a potential therapeutic agent for alleviating neuroinflammatory processes in neurodegenerative diseases."I was inclined to talk about the Yuan paper because of the various 'connections' that have been made between oxytocin and autism (see here). With a growing interest in the oxytocin-autism connection in the peer-reviewed literature, this nonapeptide (9 amino acids long) has attracted quite a few researchers to its cause  as a function of the idea that: "Oxytocin increases the salience of social stimuli and promotes parental nurturing and social bonds" . As per my interpretation of the current state of the oxytocin-autism research base, there are some interesting results available but once again, universal 'effects' are nowhere to be seen - Autisms, people. Autisms. The Yuan and other results focusing on the 'anti-neuroinflammatory' activity of oxytocin perhaps add another dimension to the possible hows and whys of efficacy when it comes to a label like autism. That also a growing number of people are coming around to the idea that neuroinflammation might be a facet of 'some' autism (see here) and including some mention of microglia (see here) offers an additional correlate to add into the future research mix. Could those with autism who have more prominent signs of neuroinflammatory issues potentially be 'best responders' to oxytocin for example? I did also wonder whether the idea that inflammation or inflammatory issues might feature in complex behaviours like social cognitive processing (see here) could provide another explanation for some of the reported results observed following use of oxytocin in [some] autism?Much more research is indicated but again the message is... don't be too dogmatic when it comes to pharmacological targets and actions of medicines indicated for conditions such as autism. You might just end up being surprised...---------- Yuan L. et al. Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice. Journal of Neuroinflammation. 2016; 13:77. Okamoto Y. et al. The Potential of Nasal Oxytocin Administration for Remediation of Autism Spectrum Disorders. CNS Neurol Disord Drug Targets. 2016 Apr 13. Young LJ. & Barrett CE. Neuroscience. Can oxytocin treat autism? Science. 2015 Feb 20;347(6224):825-6.----------Yuan L, Liu S, Bai X, Gao Y, Liu G, Wang X, Liu D, Li T, Hao A, & Wang Z (2016). Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice. Journal of neuroinflammation, 13 (1) PMID: 27075756... Read more »
Yuan L, Liu S, Bai X, Gao Y, Liu G, Wang X, Liu D, Li T, Hao A, & Wang Z. (2016) Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice. Journal of neuroinflammation, 13(1), 77. PMID: 27075756
The whole of human intelligence, right at your fingertips. Sure it might not make the layman an engineer or physicist, but if we want to learn about a particular topic the internet can give us that information. But you better hold on tight before you lose it. New research finds retweeting or otherwise sharing information creates a “cognitive overload” that interferes with learning and retaining what you’ve just seen.
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Jiang, T., Hou, Y., & Wang, Q. (2016) Does micro-blogging make us “shallow”? Sharing information online interferes with information comprehension. Computers in Human Behavior, 210-214. DOI: 10.1016/j.chb.2016.02.008
Human behavioral scientists argue that extra-pair copulation is adaptive in human females, as through extra-pair copulation, women can acquire good genes from other potential mates. This is suggested because it is found that women experience greater sexual attraction to particular extra-pair men, but not their own partners, during their highest peak of fertility (Gangestad & […]... Read more »
Greeff, J., & Erasmus, J. (2015) Three hundred years of low non-paternity in a human population. Heredity, 115(5), 396-404. DOI: 10.1038/hdy.2015.36
Treating immune disorders might have gotten easier with a new mouse model.... Read more »
Beura, L., Hamilton, S., Bi, K., Schenkel, J., Odumade, O., Casey, K., Thompson, E., Fraser, K., Rosato, P., Filali-Mouhim, A.... (2016) Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature, 532(7600), 512-516. DOI: 10.1038/nature17655
Mestas, J., & Hughes, C. (2004) Of Mice and Not Men: Differences between Mouse and Human Immunology. The Journal of Immunology, 172(5), 2731-2738. DOI: 10.4049/jimmunol.172.5.2731
Signatures of Mutational Processes Extracted from the Mutational Catalogs of 21 Breast Cancer Genomes. Credit:http://dx.doi.org/10.1016/j.celrep.2012.12.008Cancer is the second leading cause of death worldwide, with approximately 14 million new cases and 8.2 million cancer related deaths each year (Source: WHO). A family history of cancer typically increases a person's risk of developing the disease, yet most cancer cases have no family history at all. This suggests that a combination of both genetics and environmental exposures contribute to the etiology of cancer. In this context, "genetics" means the genetic make-up we are born with and inherited from our parents. For example, women born with specific mutations in the BRCA1 and BRCA2 genes are known to have a much higher risk of developing breast cancer later in life.However, besides the genetic make-up we carry from birth, there are many geographical and environmental factors that contribute to the risk of cancer. For example, the incidence of breast cancer is over 4 times higher in North and West Europe compared to Asia and Africa (Source: WHO). Stomach cancer, on the other hand, is much more prevalent in Asia than the US. If you think that this may be linked to the genetic differences across ethnicities, think again. The National Cancer Institute published a summary of several studies that compared the incidence of first and second generation immigrants in the US with the local population. They found that:"cancer incidence patterns among first-generation immigrants were nearly identical to those of their native country, but through subsequent generations, these patterns evolved to resemble those found in the United States. This was true especially for cancers related to hormones, such as breast, prostate, and ovarian cancer and neoplasms of the uterine corpus and cancers attributable to westernized diets, such as colorectal malignancies."According to the World Health Organization (WHO), "around one third of cancer deaths are due to the 5 leading behavioral and dietary risks: high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, alcohol use."Cancer is the result of a series of cellular mechanisms gone awry: every time a cell divides, somatic mutations accumulate in the cell's genome. These are not mutations we are born with, inherited from our parents. Rather, these are changes that accumulate in certain cells as we grow old and are not the same across all cells in the body. Many environmental exposures contribute to this process and affect the rate at which these mutations accumulate. However, cells have various mechanisms that are normally able to repair harmful mutations or, when the damage is beyond repair, to trigger cell death. The immune system is also "trained" to recognize cancer cells and destroy them.When all these defense mechanisms fail, cancer cells start dividing uncontrollably.As a result, all cancer cells carry a number of somatic mutations that set them apart from healthy cells, and some tend to be the same across different cancer patients: for example, specific mutational patterns found in lung cancer have been attributed to tobacco exposure and were indeed reproduced in animal models. Another set of mutations has been attributed to UV exposure and has been found in skin cancers [1, 2].This prompts the ambitious question: can we find common mutations across individuals with the same cancer? And how many of these mutational patterns that are common across individuals can we attribute to particular exposures and/or biological processes? Distinguished postdoctoral researcher Ludmil Alexandrov, from the Los Alamos National Laboratory, has been working on this problem since his he was a PhD student at the Wellcome Trust Sanger Institute."It's like lifting fingerprints," Alexandrov explains. "The mutations are the fingerprints, but now we have to do the investigative work and find the 'perpetrator', i.e., the carcinogens that caused them." During his graduate studies, under the supervision of Mike Stratton of the Wellcome Trust Sanger Institute, Alexandrov developed a mathematical model that, given the cancer genomes from a number of patients, is able to pick the "common signals" across the patients -- i.e. mutation patterns that are common across the patients -- and classify them into "signatures." "When formulated mathematically," Alexandrov explains, "the question can be expressed as the classic 'cocktail party' problem, where multiple people in a room are speaking simultaneously while several microphones placed at different locations are recording the conversations. Each microphone captures a combination of all sounds and the problem is to identify the individual conversations from all the recordings." Taking from this analogy, each cancer genome is a "recording", and the task of the mathematical model is to reconstruct each conversation, in other words, the mutational patterns. These are sets of somatic mutations that are the observed across the cancer genomes and that characterize certain types of cancers.In 2013, Alexandrov and colleagues analyzed 4,938,362 mutations from 7,042 patients, spanning 30 different cancers, and extracted more than 20 distinct mutational signatures . "Some patterns were expected, like the known ones caused by tobacco and UV light," Alexandrov says. "Others were completely new."Of the new signatures found, many are involved in defective DNA repair mechanisms, suggesting that drugs targeting these specific mechanisms may benefit cancers exhibiting these signatures . But the most exciting part of this research will be finding the 'perpetrator' or, as Alexandrov explains, the mutations triggered by carcinogens like tobacco, UV radiation, obesity, and so on. The challenge will be to experimentally associate these mutational patterns to the exposures that caused them. In order to do this, the scientists will have to expose cultured cells and model organisms to known carcinogens and then analyze the genomes of the experimentally induced cancers.In the meantime, the signatures found so far are only the beginning: Alexandrov and colleagues have teamed up with the Los Alamos High Performance Computing Organization in order to analyze the genomes of almost 30,000 cancer patients. "The amount of data we will have to handle for this task is enormous, on the order of petabytes," Alexandrov says. "Few places in the world have the capability to handle this many data. Under normal circumstances, it takes months to answer a question on 10 petabytes of data. The supercomputing facility at Los Alamos can provide an answer within a day." Because of his research, in 2014 Alexandrov was listed by Forbes magazine as one of the “30 brightest stars under the age of 30” in the field of Science and Healthcare. In 2015 he was awardedthe AAAS Science & SciLifeLab Prize for Young Scientists in the category Genomics and Proteomics  and the Weintraub Award for Graduate Research. He is now the recipient of the prestigious Oppenheimer fellowship at Los Alamos National Laboratory.Disclaimer: Elena E. Giorgi is a computational biologist in the Theoretical Division of the Los Alamos National Laboratory. She does not represent her employer’s views. LA-UR-16-xxxx.ReferencesSiegel, R., Miller, K., & Jemal, A. (2015). Cancer statistics, 2015 ... Read more »
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale AL.... (2013) Signatures of mutational processes in human cancer. Nature, 500(7463), 415-21. PMID: 23945592
Alexandrov LB, Nik-Zainal S, Siu HC, Leung SY, & Stratton MR. (2015) A mutational signature in gastric cancer suggests therapeutic strategies. Nature communications, 8683. PMID: 26511885
by Rita Handrich in The Jury Room
It’s time to run down some articles that are curious, but not substantial enough to justify a full blog post. Once again, we have kept a few pearls in our virtual filing cabinet, and have combined them here for your curiosity and possibly entertainment. This is one of those combination posts that will offer you […]
The Fear of Missing Out (FoMO) Scale
Red, redux: Men won’t pay attention to Tammy in red
Does this mean we need to pay no attention to 1 in 10 research findings?
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Roberts, J., & David, M. (2016) My life has become a major distraction from my cell phone: Partner phubbing and relationship satisfaction among romantic partners. Computers in Human Behavior, 134-141. DOI: 10.1016/j.chb.2015.07.058
Drug Discovery, Part III
How is a an Initial Hit optimised and turned into a Lead Compound?... Read more »
They say you should never mix business and pleasure but in reality many of us find that we become friends with the people who we work with. No wonder, when you consider the hours spent together and the deep bonds formed through collaboration and sharing the highs and lows of the job.A new study in Personnel Psychology is among the first to examine the effects on job performance of having more "multiplex relationships" – colleagues you work with directly who are also your friends outside of work. The researchers say these relationships are "a mixed blessing", but on balance they found that the more of them people had, the better their work performance as judged by their supervisors. Jessica Methot and her colleagues first surveyed 301 staff at a large insurance company in southeastern United States. These staff, who had varied roles across the firm, provided a list of 10 colleagues they worked with closely in pursuit of their responsibilities and 10 staff who they considered to be friends and who they socialised with outside of work. The more overlap there was between a person's two lists, the more multiplex relationships they had. The participants also completed measures of emotional exhaustion and work-related positive emotions. Four weeks later, the participants' supervisors were contacted and rated the participants' job performance.The more multiplex relationships that participants had, the better their job performance. What's more, this was explained in part by the fact that such relationships were associated with experiencing more positive work-related emotions, like feeling excited and proud. In short, being friends with more of colleagues appeared to be good for staff and for their employer.However, the picture gets a little more complicated because the researchers dug deeper and found that multiplex relationships were also associated with more emotional exhaustion – presumably because of the effort involved in maintaining more complex relationships and of providing support to friends. In turn, emotional exhaustion was related to poorer work performance, hence the researchers describing workplace friendships as a mixed blessing. Overall though, the benefits to work performance outweighed the costs.The second study was similar but involved 182 workers at three shops and six restaurants. This time the participants also completed measures of the emotional support, trust, felt obligation, and "maintenance difficulty" (the effort of sustaining and juggling relationships) experienced in their work relationships. The results were similar, with more multiplex relationships again correlating with superior work performance – and this time the association was explained in part by feelings of greater trust towards colleagues who are also friends. But once more, although the overall association was positive, there were signs that these relationships can be a mixed blessing – the more multiplex relationships a person had, the more they tended to report having difficulties maintaining their relationships, which in turn was related to poorer job performance.We need to be aware these studies were correlational so they haven't demonstrated that work friendships causes better job performance, although that is certainly a plausible interpretation, especially in light of the mediating factors that the researchers identified. Given that having more friends at work appears to be beneficial overall, Methot and her colleagues recommended that "organisations should focus on practices that promote friendship among coworkers who can interact for work-related purposes" such as introducing friendly competition between staff, or implementing social intranet systems "that simultaneously allow employees to collaborate and share task information while getting to know each other on a social level"._________________________________ Methot, J., Lepine, J., Podsakoff, N., & Christian, J. (2016). Are Workplace Friendships a Mixed Blessing? Exploring Tradeoffs of Multiplex Relationships and their Associations with Job Performance Personnel Psychology, 69 (2), 311-355 DOI: 10.1111/peps.12109 Post written by Christian Jarrett (@psych_writer) for the BPS Research Digest.Our free weekly email will keep you up-to-date with all the psychology research we digest: Sign up!
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Methot, J., Lepine, J., Podsakoff, N., & Christian, J. (2016) Are Workplace Friendships a Mixed Blessing? Exploring Tradeoffs of Multiplex Relationships and their Associations with Job Performance. Personnel Psychology, 69(2), 311-355. DOI: 10.1111/peps.12109
"Children with higher urinary DMP [dimethylphosphate] concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD [attention-deficit hyperactivity disorder]."So said the results presented in the paper by Yu and colleagues  who looking at "97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age" examined urine and blood samples for various factors including "biomarkers of OP [organophosphate] pesticide exposure." They concluded that, adjusting for creatinine, urine levels of DMP but not other dialkylphosphate (DAP) metabolites were higher in the ADHD group compared with the non-ADHD group. Further: "Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD." At the same time, Yu et al also reported nothing very much to see when it came to blood lead levels (BLLs) between the groups.This is not the first time that examination of urinary metabolites of OPs have turned up something of a potential relationship with behavioural outcomes related to ADHD. The paper by Bouchard and colleagues  also reported a possible connection supporting a "hypothesis that organophosphate exposure, at levels common among US children, may contribute to ADHD prevalence." There too urine was the analytical medium and dialkylphosphate concentrations the target compounds. This and other research looking at this issue have led to statements  to the effect that: "Children's exposures to pesticides should be limited as much as possible." I don't think many people would disagree with that sentiment.I've talked about OPs quite a bit on this blog (see here and see here) and how various conditions/labels might be 'associated' with this class of compounds either when used as insecticides or as something rather more ominous. I've tried not to be too alarmist about the possibility of a connection with health because OPs do serve an important purpose (as an insecticide) and have probably saved quite a few lives as a result. But it is getting increasingly difficult to ignore the possibility that this and other classes of pesticides either alone or in combination with other factors, seem to be implicated in various conditions/labels and more needs to be done looking at the hows and whys. This can however be done without scaremongering.The Yu results whilst interesting are not however without some cautions. DAP metabolites as markers for OP exposure still requires further investigations , not least from which specific OP they are derived from. That other factors such as exposure to second-hand tobacco smoke might also link into the presentation of specific metabolites such as DMP  is another consideration. Continuing the theme that combinatorial exposures might also exert an effect  other research illustrates how difficult it might be to pin one specific type of exposure to specific behavioural outcomes. And then also we have the added layer of complexity that is the genetics of xenobiotic metabolism with specific focus on OPs. Relationships are likely to be pretty complicated as a result.Having said all that does not however mean that results like the ones from Yu et al can be just brushed under the carpet...Music to close, and having watched Guardians of the Galaxy for the Nth time last evening, all I can say is the film soundtrack is kinda cool...---------- Yu CJ. et al. Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children. Andrology. 2016 Apr 12. Bouchard MF. et al. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics. 2010 Jun;125(6):e1270-7. Roberts JR. et al. Pesticide exposure in children. Pediatrics. 2012 Dec;130(6):e1765-88. Sudakin DL. & Stone DL. Dialkyl phosphates as biomarkers of organophosphates: the current divide between epidemiology and clinical toxicology. Clin Toxicol (Phila). 2011 Nov;49(9):771-81. Jain RB. Levels of dialkylphosphate metabolites in urine among general U.S. population. Environ Toxicol Pharmacol. 2016 Feb 26;43:74-82. Osaka A. et al. Exposure characterization of three major insecticide lines in urine of young children in Japan-neonicotinoids, organophosphates, and pyrethroids. Environ Res. 2016 May;147:89-96.----------Yu CJ, Du JC, Chiou HC, Chung MY, Yang W, Chen YS, Fuh MR, Chien LC, Hwang B, & Chen ML (2016). Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children. Andrology PMID: 27070915... Read more »
Yu CJ, Du JC, Chiou HC, Chung MY, Yang W, Chen YS, Fuh MR, Chien LC, Hwang B, & Chen ML. (2016) Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children. Andrology. PMID: 27070915
Coronaviruses (CoV) are positive sense RNA viruses with a genome size of 29-32 kb with four genera (Alpha-, Beta-, Gamma- and Delta CoV) belonging to the family of the Coronaviridae within the order of Nidovirales, with the Betacoronaviruses further divided into four lineages (A-D).
Most CoV identified until now are causing severe disease only in animals including agricultural important animals such as chicken, cattle, and pigs. To date only six human CoV (HCoV) have been identified, namely HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, Severe Respiratory Syndrome (SARS)-CoV and most recently Middle Eastern Respiratory Syndrome (MERS)-CoV, although a SARS-like CoV, WIV1-CoV, replicates in primary human epithelial cells at low levels as well as in mice expressing the human SARS-CoV receptor ACE2 albeit at lower levels compared to SARS-CoV.
Here recent advances concerning the inhibition of the antiviral response with a focus on the viral orf4b and M proteins derived from MERS-CoV are discussed. ... Read more »
Chan JF, Lau SK, To KK, Cheng VC, Woo PC, & Yuen KY. (2015) Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clinical microbiology reviews, 28(2), 465-522. PMID: 25810418
Han HJ, Yu H, & Yu XJ. (2016) Evidence for zoonotic origins of Middle East respiratory syndrome coronavirus. The Journal of general virology, 97(2), 274-80. PMID: 26572912
Han, H., Wen, H., Zhou, C., Chen, F., Luo, L., Liu, J., & Yu, X. (2015) Bats as reservoirs of severe emerging infectious diseases. Virus Research, 1-6. DOI: 10.1016/j.virusres.2015.05.006
Wong LY, Lui PY, & Jin DY. (2016) A molecular arms race between host innate antiviral response and emerging human coronaviruses. Virologica Sinica, 31(1), 12-23. PMID: 26786772
Lin R, Heylbroeck C, Pitha PM, & Hiscott J. (1998) Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Molecular and cellular biology, 18(5), 2986-96. PMID: 9566918
Yang XL, Hu B, Wang B, Wang MN, Zhang Q, Zhang W, Wu LJ, Ge XY, Zhang YZ, Daszak P.... (2015) Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus. Journal of virology, 90(6), 3253-6. PMID: 26719272
Menachery VD, Yount BL Jr, Sims AC, Debbink K, Agnihothram SS, Gralinski LE, Graham RL, Scobey T, Plante JA, Royal SR.... (2016) SARS-like WIV1-CoV poised for human emergence. Proceedings of the National Academy of Sciences of the United States of America. PMID: 26976607
Munster, V., Adney, D., van Doremalen, N., Brown, V., Miazgowicz, K., Milne-Price, S., Bushmaker, T., Rosenke, R., Scott, D., Hawkinson, A.... (2016) Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis). Scientific Reports, 21878. DOI: 10.1038/srep21878
Yang Y, Ye F, Zhu N, Wang W, Deng Y, Zhao Z, & Tan W. (2015) Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets. Scientific reports, 17554. PMID: 26631542
Siu KL, Kok KH, Ng MH, Poon VK, Yuen KY, Zheng BJ, & Jin DY. (2009) Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex. The Journal of biological chemistry, 284(24), 16202-9. PMID: 19380580
Matthews, K., Schäfer, A., Pham, A., & Frieman, M. (2014) The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity. Virology Journal, 11(1). DOI: 10.1186/s12985-014-0209-9
Siu, K., Yeung, M., Kok, K., Yuen, K., Kew, C., Lui, P., Chan, C., Tse, H., Woo, P., Yuen, K.... (2014) Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response. Journal of Virology, 88(9), 4866-4876. DOI: 10.1128/JVI.03649-13
Lui PY, Wong LY, Fung CL, Siu KL, Yeung ML, Yuen KS, Chan CP, Woo PC, Yuen KY, & Jin DY. (2016) Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3. Emerging microbes . PMID: 27094905
Matthews KL, Coleman CM, van der Meer Y, Snijder EJ, & Frieman MB. (2014) The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling. The Journal of general virology, 95(Pt 4), 874-82. PMID: 24443473
Thornbrough JM, Jha BK, Yount B, Goldstein SA, Li Y, Elliott R, Sims AC, Baric RS, Silverman RH, & Weiss SR. (2016) Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation. mBio, 7(2). PMID: 27025250
Li Y, Banerjee S, Wang Y, Goldstein SA, Dong B, Gaughan C, Silverman RH, & Weiss SR. (2016) Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses. Proceedings of the National Academy of Sciences of the United States of America, 113(8), 2241-6. PMID: 26858407
Banerjee S, Chakrabarti A, Jha BK, Weiss SR, & Silverman RH. (2014) Cell-type-specific effects of RNase L on viral induction of beta interferon. mBio, 5(2). PMID: 24570368
Malathi, K., Dong, B., Gale, M., & Silverman, R. (2007) Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature, 448(7155), 816-819. DOI: 10.1038/nature06042
Shao Q, Xu W, Guo Q, Yan L, Rui L, Liu J, Zhao Y, & Li Z. (2015) RIG-I from waterfowl and mammals differ in their abilities to induce antiviral responses against influenza A viruses. The Journal of general virology, 96(Pt 2), 277-87. PMID: 25371516
Xu W, Shao Q, Zang Y, Guo Q, Zhang Y, & Li Z. (2015) Pigeon RIG-I Function in Innate Immunity against H9N2 IAV and IBDV. Viruses, 7(7), 4131-51. PMID: 26205406
Neuroscientists have a schizophrenic view of how neurons. On the one hand, we say, neurons are ultra-efficient and are as precise as possible in their encoding of the world. On the other hand, neurons are pretty noisy, with the variability in … Continue reading →... Read more »
The paper introducing our new tree visualisation tool Phylo.io was just published in MBE.
Yet another tool to display trees, you might say, and indeed, so it is. But for all the tools that have been developed over the years, there are very few that scale to large trees, make it easy to compare trees side-by-side, and simply run in a browser on any computer or mobile device.
To fill this gap, we created Phylo.io.
Story behind the paper
The project started as a student summer internship project, with the aim of producing a tree visualiser that facilitates comparison of trees built on the same set of leaves. After reading the project description, Oscar Robinson, a brilliant student from the Computer Science department at UCL, decided to work on this project during a three month internship. He saw a chance to apply his experience in the development of web tools and to develop his knowledge in the field of data visualisation, one of his major interests.
What is phylo.io and what can it do?
Phylo.io is a web tool that works in any modern browser. All computations are performed client-side and the only restriction on performace is the machine it is running on. Trees can be input in Newick and Extended Newick format. Phylo.io offers many features that other tree viewers have. Branches can be swapped, the rooting can be changed, the thickness, font and other parameters are adaptable. Many of these operations can be performed directly by clicking on a branch or a node in the tree. Importantly, it features an automatic subtree collapsing function: this facilitates the visualisation of large trees and hence the analysis of splits that are deep in the tree.
Next to basic tree visualisation/manipulation it features a compare mode. This mode allows to compare two trees computed using different tools or different models. Similarities and differences are highlighted using a colour scheme directly on the individual branches, making it clear where the differences in two topologies actually are. Additionally, since the output of different tools provides trees with very different rootings and leaf order, Phylo.io has a function to root one of the trees according to the other one and adapt the order of the leaves according to a fixed tree.
How do you use phylo.io?
In order to save you some time below you find a screencast explaining the major features and usage of Phylo.io to visualise and compare trees.
Robinson, O., Dylus, D., & Dessimoz, C. (2016). Phyla.io: interactive viewing and comparison of large phylogenetic trees on the web
Molecular Biology and Evolution DOI: 10.1093/molbev/msw080
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Robinson, O., Dylus, D., & Dessimoz, C. (2016) Phyla.io: interactive viewing and comparison of large phylogenetic trees on the web . Molecular Biology and Evolution. DOI: 10.1093/molbev/msw080
It was the summer of 1882, and grape farmers in the Médoc region of southwest France (north of Bordeaux, on the Atlantic coast) had a problem.Schoolchildren (or university students, or just anyone travelling the roads along which the grapevines grew, depending on what source you're reading) were pilfering their grapes. To try and ward them off, some farmers decided to dissolve some slaked lime and copper sulfate in water and spray it on their grapevines closest to the roads. The idea was... Read more »
Pimentel J, & Marques F. (1969) 'Vineyard sprayer's lung': A new occupational disease. Thorax, 24(6), 678-688. DOI: 10.1136/thx.24.6.678
I recently pointed out that the widespread belief that migrants refuse to learn the language of their new country does not stack up against the realities of adult language learning. I summarized the research that shows that adult language learning is complex and difficult and rarely an all-out success; to blame migrants for their failure to learn a new language (well) is adding insult to injury.
The German-language club (“Stammtisch”) in New York founded by Graf met until 2015 (Source: derstandard.at)
These well-established facts do not mean that individual migrants may not actively choose not to learn a new language. Unfortunately, we know surprisingly little about people who refuse to learn a new language. Partly, this is a problem of methods: how would one collect data about language refusal? While many non-migrants in Western societies believe themselves surrounded by language shirkers, it seems unlikely that advertising for research participants “who are refusing to learn the national language” would produce too many volunteers. Not only because, as I have shown, unadulterated language refusal is rare but also because migrants who actually might refuse to learn the language of their new society are, of course, in a double bind that would make it difficult to admit to language shirking.
Does that mean we are stuck between believing either those who see themselves surrounded by language shirkers or those who doubt their existence – depending on whether we are inclined to take a pessimistic or an optimistic view of our fellow humans? Not quite.
Let me introduce an unabashed language shirker, the German-language author Oskar Maria Graf, who spent almost half of his life in New York but was quite open about the fact that he had little interest in even trying to learn English.
Oskar Maria Graf (1894-1967) was a Bavarian “provincial author” (as he called himself) with an anarchist bent. As a committed socialist and pacifist, and an active participant in the socialist Munich revolution of 1919, which had established a short-lived Soviet republic in Bavaria, Graf fled Germany immediately after Hitler came to power in early 1933. He spent time in neighbouring Austria and Czechoslovakia but, as European countries of exile became increasingly precarious, Graf, like all German refugees, had to look for a safe haven further afield. In 1938 he and his wife were granted a US visa. They arrived in New York in September 1938 and continued to live there until their deaths.
Oskar Maria Graf, 1927, painting by Georg Schrimpf (Source: Wikipedia)
Back home, Graf had been a successful author during the interwar period. An autodidact (he left school when he was twelve years old and was apprenticed as a baker), Graf specialized in social realism with a focus on local Bavarian themes. After he had to leave his native country, the whole basis of his literary work – based as it was in the German language and the close observation of the mundane lives of Bavarian peasants – disappeared. He continued to write in German and his best-known book, Das Leben meiner Mutter (“The life of my mother”), was, in fact, written in exile but the success of his Munich years eluded him. Between 1933 and 1945, his opportunities to publish in German were severely limited; and he never returned to live in Germany even after the war despite the fact that his career was tied to German-language publishing.
Having been forced from home and wanting to retain the lost home are themes that, for Graf, are deeply connected to linguistic questions of maintaining the German language and not learning the English language. Let’s now examine what Graf’s language refusal looked like.
Graf almost celebrated the fact that he did not know how to speak English; it is a topic that comes up again and again in his later writing. A good example comes from his 1959 novel Die Flucht ins Mittelmäßige (“Taking refuge in mediocrity”), which is concerned with a group of German emigrants in New York. One of the main characters, Martin Ling, is commonly taken to be Graf’s alter ego, and Ling’s English language proficiency is introduced early in the novel as follows:
Ling had been living in New York for almost twenty years and up to now understood little more than a few indispensable English phrases. He made no efforts to improve his language skills, either; he had adopted nothing ‘American’ apart from what seemed automatically and mechanically comfortable to him. As a result, of course, he had made no progress and never got anywhere.
Ling lebte schon fast zwanzig Jahre in New York und verstand bis jetzt immer noch kaum mehr als einige notwendige englische Redewendungen. Er gab sich auch gar keine Mühe, seine Sprachkenntnisse zu vervollständigen, und ausser demjenigen, was ihm gewissermaßen automatisch-mechanisch komfortabel erschien hatte er auch sonst noch nichts ‘Amerikanisches’ angenommen. Dadurch kam er natürlich nie vorwärts und weiter. (Flucht ins Mittelmäßige, p. 8)
That his lack of English language proficiency was not only coy self-effacement has been confirmed by the observations of many others who knew him in New York. Lisa Hoffman, for instance, who was his lover in the 1950s, described in a 2010 newspaper interview how his English was j... Read more »
Azuélos, D. (2008) L'exil dans l'exil Les stratégies linguistiques contradictoires des exilés aux États-Unis (Thomas Mann, Klaus Mann, Hans Sahl, Oskar Maria Graf). Études Germaniques, 252(4), 723. DOI: 10.3917/eger.252.0723
Back in 2013, I wondered if we would ever discover the neural basis of spontaneous thoughts. Why, I asked, do certain ideas just "pop" into our minds at particular times? Now a new paper published in Neuroimage, Canadian neuroscientists Melissa Ellamil and colleagues reports on the neural basis of spontaneous thoughts.
Ellamil et al. recruited a group of 18 volunteers, all of whom were highly experienced practitioners of mindfulness meditation. These individuals were selected, the authors... Read more »
Ellamil M, Fox KC, Dixon ML, Pritchard S, Todd RM, Thompson E, & Christoff K. (2016) Dynamics of neural recruitment surrounding the spontaneous arising of thoughts in experienced mindfulness practitioners. NeuroImage. PMID: 27114056
"Parents ultimately wanted therapists to produce positive outcomes for their children and were willing to sacrifice other desired qualities, as long as the therapy program was effective."and"The SLPs [Speech-Language Pathologists] expressed strong support for evidence-based practice (EBP) and indicated that they thought parents expected their children would be provided with evidence-based interventions."Those quotes come from two papers recently published in the same journal; the first by Amelia Edwards and colleagues  attempting to identify "the qualities parents seek in therapists who work with their children with ASD [autism spectrum disorder]" and the second from David Trembath and colleagues  titled: 'What do speech-language pathologists think parents expect when treating their children with autism spectrum disorder?'Providing what is a quite fascinating (albeit small scale) insight into the expectations of therapists and parents who use therapists for their children when it comes to autism, these papers put some science to what many people might already have suspected. The Edwards paper also carried an important sentence in the paper title - "More than blowing bubbles" - implying how positive real world outcomes are always going to be the most important elements of any intervention program when it comes to autism or indeed, any other label. The idea that avenues towards those positive outcomes should be 'evidence-based' is perhaps a sentiment noted in the views and opinions of [many of] those professionals delivering intervention but might not necessarily be first and foremost for parents whose natural instinct is to want the best for 'their child'.The link between the concept of 'evidence-based' and autism is particularly interesting. A few years back I covered a paper by Gary Mesibov & Victoria Shea  (see here) carrying the idea that there may be both "benefits and limitations" when it came to the application of evidence-based policy and autism intervention. The sorts of variables that made evidence-based policy difficult when applied to autism ranged from the vast heterogeneity present under the label (or labels) to the idea that the gold-standard 'randomised controlled trial' (RCT) might not be all that suitable when assessing comprehensive intervention programs that for example, contain multiple elements. In subsequent years we've also learned that autism rarely appears in some sort of diagnostic vacuum (see here), something that might also impact on evidence-based policy with regards to intervention (see here). For scientific puritans, the Mesibov-Shea discussions could be construed as heresy. For me, there was some substance in their arguments and some lessons on how autism research in particular, needs to adapt and change away from the notion that 'autism' universally covers everyone with autism in terms of similar aetiology and pathology. Endophenotypes and 'snowflakes' people...It should of course be recognised that quite a lot of the 'not-knowing' when it comes to the autism spectrum has set the field of autism intervention up for a variety of 'unusual' proposals for interventions, many of which have not been suitably scientifically tested (see here). Some are even downright unsafe but are still pursued for one reason or another, probably pertinent to that opening sentence on 'effectiveness' and no doubt playing into other emotions as and when a child presents with autism . Feelings run high on this topic as I once again refer you to the post by Tom Insel on the 'kingdoms of autism' (see here) with a suggestion that different views be respected but at the same time, safety should be paramount.Acknowledging that there is no 'one-size-fits-all- approach when it comes to autism intervention and that for some, mention of the words 'therapy' and 'intervention' are not necessarily high on their list of priorities, the Edwards and Trembath papers invite quite a bit more investigation. The possibility of a 'disconnect' between what parents want for their children and what therapists are currently able to deliver for their children represents something that could potentially impact on the delivery of intervention and the importance of the parent-professional relationship in this context. I'm also going to throw the paper by Paynter and colleagues  into this mix too...To close, I feel old. Jossy's Giants is 30 years old (although I'm more inclined to the Red and White)...---------- Edwards A. et al. "More than blowing bubbles": What parents want from therapists working with children with autism spectrum disorder. Int J Speech Lang Pathol. 2016 Apr 4:1-13. Trembath D. et al. What do speech-language pathologists think parents expect when treating their children with autism spectrum disorder? Int J Speech Lang Pathol. 2016 Mar 10:1-9. Mesibov GB. & Shea V. Evidence-based practices and autism. Autism. 2011 Jan;15(1):114-33. Ooi KL. et al. A meta-synthesis on parenting a child with autism. Neuropsychiatric Disease and Treatment. 2016; 12: 745-762. Paynter JM. et al. Utilisation of evidence-based practices by ASD early intervention service providers. Autism. 2016. April 18.----------Edwards, A., Brebner, C., Mccormack, P., & Macdougall, C. (2016). “More than blowing bubbles”: What parents want from therapists working with children with autism spectrum disorder International Journal of Speech-Language Pathology, 1-13 DOI: 10.3109/17549507.2015.1112835Trembath, D., Hawtree, R., Arciuli, J., & Caithness, T. (2016). What do speech-language p... Read more »
Edwards, A., Brebner, C., Mccormack, P., & Macdougall, C. (2016) “More than blowing bubbles”: What parents want from therapists working with children with autism spectrum disorder. International Journal of Speech-Language Pathology, 1-13. DOI: 10.3109/17549507.2015.1112835
Trembath, D., Hawtree, R., Arciuli, J., & Caithness, T. (2016) What do speech-language pathologists think parents expect when treating their children with autism spectrum disorder?. International Journal of Speech-Language Pathology, 1-9. DOI: 10.3109/17549507.2016.1139625
Why does one person who tries cocaine get addicted, while another might use it and then leave it alone? Why do some people who kick a drug habit manage to stay clean, while others relapse? And why do some families seem more prone to addiction than others? According to a new study, the road to answering these questions may have a lot to do with specific genetic factors that vary from individual to individual.
... Read more »
Flagel, S., Chaudhury, S., Waselus, M., Kelly, R., Sewani, S., Clinton, S., Thompson, R., Watson, S., & Akil, H. (2016) Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model. Proceedings of the National Academy of Sciences, 201520491. DOI: 10.1073/pnas.1520491113
Happiness. It’s something we all strive for, but how do we measure it — as a country? A global community? Not so surprisingly, researchers are turning to social media to answer these questions and more. In a newly published study, computer scientists used two years of Twitter data to measure users’ life satisfaction, a component of happiness.
... Read more »
Yang, C., & Srinivasan, P. (2016) Life Satisfaction and the Pursuit of Happiness on Twitter. PLOS ONE, 11(3). DOI: 10.1371/journal.pone.0150881
Sometimes at the climax of a Star Trek episode, the captain would yell out "Battle stations!" and send the crew scurrying frantically through the corridors. It wasn't really clear what those battle stations were. Presumably, crew members headed to posts they'd been previously assigned, and this let the whole ship react to the crisis efficiently.
Certain ants respond to a crisis by binding their bodies together into floating rafts. And like the Star Trek crew, they seem to have designated ... Read more »
Avril, A., Purcell, J., & Chapuisat, M. (2016) Ant workers exhibit specialization and memory during raft formation. The Science of Nature, 103(5-6). DOI: 10.1007/s00114-016-1360-5
We know that diet, exercise and low-stress life will keep the heart healthy. But sometimes things happen that are beyond our control. Thanks to more coordinated, faster emergency response and improved treatment, heart attacks aren't as deadly as they used to be. But survivors still face a substantial risk of further cardiovascular events. How to restore after a heart attack and prevent another one? What to do besides obvious things such as taking medications, reducing stress, calories, avoiding urban air pollution and getting rid of bad lifestyle habits like smoking? Dietary fiber helps to lower cholesterol levels (as it inhibits cholesterol synthesis, increases the production of short-chain fatty acid and the rate of bile excretion), blood pressure, glucose absorption, improving insulin sensitivity, and increasing levels of antioxidants. A high-fiber diet, in general, was associated with a 31% reduction in dying from any cause and a 35% reduction in death from heart disease among over 4 thousand heart attack survivors from the Health Professionals Study and the Nurses’ Health Study.More recent Harvard study went a step further analyzing the types of fiber consumed by thousands of men and women who survived a first myocardial infarction (MI). All participants of the study increased their average dietary fiber intake after MI, and the greater the increase, the lower was the risk of subsequent all cause and cardiovascular mortality. among cereal fiber, fruit fiber, and vegetable fiber, only intake of cereal fiber was strongly inversely associated with lower all cause and cardiovascular mortality: pooled hazard ratio 0.73 (0.58 to 0.91) for all cause mortality, 0.72 (0.52 to 0.99) for cardiovascular mortality. In the general population, a 20-40% risk reduction in coronary heart disease has consistently been observed among those who consume fiber-rich whole grains regularlyAn earlier study of over 31,000 California Seventh-day Adventists found a 44% reduced risk of nonfatal coronary heart disease and an 11% reduced risk of fatal coronary heart disease for those who ate whole wheat bread compared with those who ate white bread.One minor change in diet could, indeed, save a life. Don't overdo it on the proteinLow carbohydrate plant diets might be beneficial in reducing blood pressure and reducing cholesterol.Yet, Dr Shanshan Li and her Harvard colleagues did not find a health benefit for heart attack survivors from a low carbohydrate diet even if it was low in fat and came from plant sources.Greater adherence to a low carbohydrate diet high in animal sources of fat and protein was associated with higher all-cause and cardiovascular mortality post-MI.According to the Institute of Medicine. healthy individuals should get at least 10% of their daily calories, but not more than 35%, from protein. Heart attack survivors in the Harvard and the Nurses’ Health Study ate from 15% to 20% protein (65 to 40% carbohydrates) and the lowest intake of protein seemed to be the best. It also correlated with the lowest intake of fat. Associations between the animal-based low carbohydrate diets and mortality were diminished after additionally adjusting for saturated fat.A few older studies suggested that low carbohydrate plant-based diet may slightly decrease coronary heart disease in women and heart-healthy individuals, but there might be different dietary benefits in those survived from a heart attack. Plant diets are definitely good for restoring the hearts. A study by Cleveland clinic found that a plant-based diet in conjunction with cholesterol-reducing medication reversed heart disease in 70% of patients over a 12-year period. Vegetable oils high in linoleic acid (afflower oil, soybean oil, sunflower oil, and cottonseed oil.), though, failed to reduce heart disease and overall mortality and seemed to be actually worse for heart health than eating butter.Nuts - eaten several times a week in small amounts - shown a consistent 30% to 50% lower risk of myocardial infarction, sudden cardiac death, or cardiovascular disease, as seen from several of the largest cohort studies, including the Adventist Study, the Iowa Women’s Health Study, the Nurses’ Health Study, and the Physicians’ Health Study.The Stanford Coronary Risk Intervention Project followed 300 people with coronary artery disease for four years and found the best predictor of new coronary blockages was dietary fat intake. As fat intake rose, the number of coronary blockages rose. Those patients with the lowest intake of dietary fat (about 10% to 15%) had the greatest amount of improvement and plaque shrinkage.... Read more »
Li S, Flint A, Pai JK, Forman JP, Hu FB, Willett WC, Rexrode KM, Mukamal KJ, & Rimm EB. (2014) Low carbohydrate diet from plant or animal sources and mortality among myocardial infarction survivors. Journal of the American Heart Association, 3(5). PMID: 25246449
Li S, Flint A, Pai JK, Forman JP, Hu FB, Willett WC, Rexrode KM, Mukamal KJ, & Rimm EB. (2014) Dietary fiber intake and mortality among survivors of myocardial infarction: prospective cohort study. BMJ (Clinical research ed.). PMID: 24782515
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