TDP-43 is a DNA/RNA binding protein whose cytoplasmic aggregation is associated with neuronal death in ALS and frontotemporal lobar degeneration (FTLD). TDP-43 has multiple cellular functions and shuttles between the nucleus and cytoplasm. However, in ALS and FTLD nuclear clearance of TDP-43 results in increased cytoplasmic localisation – a precursor to TDP-43 aggregation and stress granule formation. The mechanisms that regulate TDP-43 transport are not well understood but new research from Xia et al. (2015) has uncovered a role for FLCN in its nuclear export and the formation of stress granules.... Read more »
Xia Q, Wang G, Wang H, Hu Q, & Ying Z. (2015) Folliculin, a tumor suppressor associated with Birt-Hogg-Dubé (BHD) syndrome, is a novel modifier of TDP-43 cytoplasmic translocation and aggregation. Human molecular genetics. PMID: 26516189
"Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME [Chronic fatigue syndrome/myalgic encephalomyelitis]."That was the headline finding from the study by Per Magnus and colleagues  looking at whether large population data might provide some clues about 'associated' variables when it comes to the various debilitating conditions headed under the terms CFS/ME.I'm blogging at a slight disadvantage with regards to the Magnus study because I don't yet have the full-text paper. Looking at the source data - "Using the unique personal identification number assigned to everybody who is registered as resident in Norway" - and observing some notable names on the authorship list, I'm inclined to suspect that this study might have some MoBa undertones (see here) bearing in mind the focus on the "complete Norwegian population" not just pregnant women and their offspring. Indeed, other research from this authorship group provides some further clues about data derivation .Focusing on those specifically diagnosed with CFS/ME - "diagnostic code G93.3 in the International Classification of Diseases, Version 10" researchers calculated hazard ratios (HRs) for CFS/ME "after influenza infection and/or vaccination." A few details emerged including:"The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk." At this point I might direct you towards some details on the difference between incidence and prevalence.Influenza infection seemed to confer something of an enhanced risk for CFS/ME as per the finding of an adjusted HR of 2.04 (95% CI: 1.78-2.33). That being said, the authors report "no indication of increased risk of CFS/ME after [pandemic] vaccination." This has potentially important public health implications (see here).They conclude by suggesting that such natural infection = increased risk of CFS/ME vs. antigenic stimulation (vaccination) = no increased risk of CFS/ME might indicate "a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME."The first thing that struck me about these findings was the 'overlap' noted with a familiar concept to this blog: maternal immune stimulation and offspring outcomes. This is the idea that immune 'stimulation' during critical periods of pregnancy might have the propensity to affect offspring developmental outcomes in a behavioural fashion (see here for example). Two of the big names in this area (Alan Brown and the late Paul Patterson) wrote rather a good review of this area focused on how some of the tools of public health such as vaccination might already be affecting the risk of development/onset of schizophrenia in relation to the maternal immune activation (MIA) model  with viruses such as influenza in mind. More detailed work is of course indicated.Without trying to equate CFS/ME with schizophrenia or any other related label, I do find it interesting that infection and the associated biological response associated with it, might show some 'connection' to CFS/ME in the same/similar way that such biology might also be involved in priming a person for later-life schizophrenia. If we've learned anything about CFS/ME this year aside from it being 'a real illness' (see here if you really needed telling) it is that in amongst the multitude of findings on the condition, there is some really interesting 'immune-related' features coming through (see here). I know the term 'immune-related features' covers a lot of ground but alongside the already tantalising idea that infection is linked to CFS/ME onset (see here) (why else would it be also referred to as post-viral fatigue syndrome), I'm talking about how infection and response to infection might so severely impact on a person and what could be done to potentially prevent it.Further work is indicated on the basis of the Magnus findings including a focus not just on influenza and CFS/ME but other biological agents such as the really, really interesting prospect of a connection between cases of CFS/ME and acute enterovirus infection  for example. Assuming that genetic make-up probably plays an important role in the handling of such viruses in relation to labels like CFS/ME, I'd like to think that research is heading in the right direction to offer viable prevention / treatment options for such devastating disorders bearing in mind the heterogeneity present ...Music: Therapy? - Nowhere.---------- Magnus P. et al. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine. 2015 Oct 13. pii: S0264-410X(15)01433-4. Bakken IJ. et al. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012. BMC Med. 2014 Oct 1;12:167. Brown AS. & Patterson PH. Maternal Infection and Schizophrenia: Implications for Prevention. Schizophrenia Bulletin. 2011;37(2):284-290. Chia J. et al. Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and viral persistence. J Clin Pathol. 2010 Feb;63(2):165-8. Zdunek M. et al. A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS. Int J Psychol Behav Sci. 2015;5(2):98-107.----------Magnus P, Gunnes N, Tveito K, Bakken IJ, Ghaderi S, Stoltenberg C, Hornig M, Lipkin WI, Trogstad L, & Håberg SE (2015). Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine PMID: 26475444... Read more »
Magnus P, Gunnes N, Tveito K, Bakken IJ, Ghaderi S, Stoltenberg C, Hornig M, Lipkin WI, Trogstad L, & Håberg SE. (2015) Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine. PMID: 26475444
When people are listening to music, their emotional reactions to the music are reflected in changes in their pupil size. Researchers from the University of Vienna and the University of Innsbruck, Austria, are the first to show that both the emotional content of the music and the listeners’ personal involvement with music influence pupil dilation. This study demonstrates that pupil size measurement can be effectively used to probe listeners’ reactions to music.... Read more »
Gingras, B., Marin, M., Puig-Waldmüller, E., & Fitch, W. (2015) The Eye is Listening: Music-Induced Arousal and Individual Differences Predict Pupillary Responses. Frontiers in Human Neuroscience. DOI: 10.3389/fnhum.2015.00619
In mountainous regions throughout much of Europe and Asia there grows an evergreen shrub by the name of Juniperus sabina (savin juniper). Being a juniper, it produces berry-like cones and is occasionally infected by members of everyone's favourite genus of sinister orange tentacled fungi, Gymnosporangium.This shrub takes no prisoners (Source)Crushing the leaves of J. sabina produces a strong unpleasant odour, a harbinger of the ability of the plant to poison many of the creatures who consume it. It contains a mixture of smelly water-insoluble compounds, which when extracted together are called its essential oil.Included in this oil are toxins capable of disrupting the growth of many of the major insect pests of cruciferous and cereal crops, such as Pieris rapae (cabbage white, a butterfly) and Tribolium castaneum (red flour beetle). Two of the insecticidal toxins produced by the plant are deoxypodophyllotoxin and deoxypicropodophyllotoxin. These are structurally related to podophyllotoxin, which is found in the roots of the American mayapple and can be used to treat warts. The anticancer drugs etoposide and teniposide, which work by selectively killing fast-growing cells, are synthesized using podophyllotoxin as a starting material.In folk medicine, J. sabina is used to treat ulcers, rheumatic diseases, coughs, and diarrhea. It also acts on the female reproductive system, and for this reason an oil derived from the tops of the plant, taken by mouth, has been used since ancient times to induce abortion. It appears to work by preventing implantation. However, this effect only occurs at toxic doses, making it an incredibly unsafe means of terminating a pregnancy. Eating the plant can cause damage to the gastrointestinal and genitourinary tracts, resulting in pain and bleeding. It also harms the brain, potentially leading to convulsions, coma, and death.Based on laboratory experiments, J. sabina essential oil appears to inhibit the welding of sugar molecules onto blood-based proteins such as insulin and hemoglobin. This process, otherwise known as glycation, underlies the various hotspots of blood vessel damage associated with diabetes (e.g. retinopathy and nephropathy). There's hope that certain components of the essential oil might one day help to prevent and treat such complications.ReferencesAsgary S, Naderi GA, Sahebkar A, Ardekani MRS, Kasher T, Aslani S, et al. 2013. Essential oils from the fruits and leaves of Juniperus sabina possess inhibitory activity against protein glycation and oxidative stress: An in vitro phytochemical investigation. Journal of Essential Oil Research 25(1):70-77.Fournier G, Baduel C, Tur N, Rusnac M. 1996. Sabinyl acetate, the main component of Juniperus sabina L'Herit. essential oil, is responsible for antiimplantation effect. Phytotherapy Research 10(5):438-440.Gao R, Gao C, Tian X, Yu X, Di X, Xiao H, Zhang X. 2004. Insecticidal activity of deoxypodophyllotoxin, isolated from Juniperus sabina L, and related lignans against larvae of Pieris rapae L. Pest Management Science 60(11):1131-1136.Goodman L, Gilman A. 1941. The pharmacological basis of therapeutics. Macmillan Company.http://www.canadaplants.ca/display.php?id=102... Read more »
Gao R, Gao C, Tian X, Yu X, Di X, Xiao H, & Zhang X. (2004) Insecticidal activity of deoxypodophyllotoxin, isolated from Juniperus sabina L, and related lignans against larvae of Pieris rapae L. Pest Management Science, 60(11), 1131-1136. DOI: 10.1002/ps.922
Accepting the notions that (i) correlation is not necessarily the same as causation and that (ii) case-control observational studies in particular are not the best way to ascertain whether A causes B, I was rather interested in the findings reported by Ido Lurie and colleagues  and that: "Recurrent antibiotic exposure is associated with increased risk for depression and anxiety but not for psychosis."Starting from the idea that: "Changes in the microbiota (dysbiosis) were suggested to increase the risk of several psychiatric conditions through neurologic, metabolic, and immunologic pathways", y'know, the old microbiota-gut-brain axis that everyone seems to be talking about these days (see here), researchers set about looking at how one particular set of agents - antibiotics - known to affect the balance of the trillions of wee beasties that call out gut home, might play a role in said relationship. Analysing "3 nested case-control studies during the years 1995–2013 using a large population-based medical record database from the United Kingdom" Lurie et al pulled in several thousand participants ("202,974 patients with depression, 14,570 with anxiety, and 2,690 with psychosis and 803,961, 57,862, and 10,644 matched controls"). Receipt of antibiotic therapy - 1 of 7 antibiotic classes - more than 1 year before an index date was the "primary exposure of interest" taking into account various other potential confounding variables.The results: "Treatment with a single antibiotic course was associated with higher risk for depression with all antibiotic groups." The risk, or rather odds ratios, wasn't massively increased but given the participant numbers was deemed significant enough to report. Further, the risk stats increased when multiple antibiotic exposures figured, potentially indicating something of a dose-dependent relationship. Authors also noted that further attention to the use of anti-fungal medicines might also figure in any further research in this area.Going back and reiterating the caveats with which I started this post, these are interesting results. The idea that the various bacteria, fungi and viruses that inhabit our gut might be doing much more than we ever truly realised is gaining some significant research traction these days (see here for example). Yes, we have to beware of the hype and inevitable sweeping generalisations that accompany the whole 'gut bugs doing more than digesting food' mantra but data are data and this recent data strengthens the calls for more research inspection in this area including on the longer-term effects of 'swallowing a grenade'. I might add that facets of the gut bacteria and depression have been talked about before in the research literature (see here).Although perhaps not looking at precisely the same aspect of the gut bacteria - behaviour link, it is timely that the Lurie paper coincides at the time of writing with some new reports coming out of this years Society for Neuroscience (SfN) conference. The headline ran with: "Probiotic bacteria may aid against anxiety and memory problems" highlighting some interesting results on the use of a daily capsule containing Bifidobacterium longum 1714 on aspects of mild anxiety and other parameters. What this and other research suggests is that when it comes to mental health and wellbeing, it may be advisable to pay due consideration to the idea of a 'gut feeling' alongside the idea that supplementing with probiotics or even eating certain foods (see here) might actually be heading to a psychiatrist near you...Music: Saint Etienne - Nothing Can Stop Us.---------- Lurie I. et al. Antibiotic Exposure and the Risk for Depression, Anxiety, or Psychosis: A Nested Case-Control Study. J Clin Psychiatry. 2015. October 15.----------Lurie, I., Yang, Y., Haynes, K., Mamtani, R., & Boursi, B. (2015). Antibiotic Exposure and the Risk for Depression, Anxiety, or Psychosis The Journal of Clinical Psychiatry DOI: 10.4088/JCP.15m09961... Read more »
Lurie, I., Yang, Y., Haynes, K., Mamtani, R., & Boursi, B. (2015) Antibiotic Exposure and the Risk for Depression, Anxiety, or Psychosis. The Journal of Clinical Psychiatry. DOI: 10.4088/JCP.15m09961
A group at the Pasteur Institute succeeded in generating a bioluminescent strain of Leptospira interrogans. Their study was published last year in PLOS Neglected Tropical Diseases.The benefit of having a bioluminescent strain is that infections of small laboratory rodents can be monitored without sacrificing the animals. Instead, the animals are placed in a special whole-body imager that detects light emitted from the bodies. The location of the infection in the animals can be determined from the images, and the light intensity measured by the imager gives an idea of the bacterial load in infected tissues. After imaging, the animal can be returned to its cage, and additional images of the same animal can be taken later as the infection progresses.Another advantage of using bioluminescent bacteria is that the luciferase reaction requires ATP, meaning that the bacteria must be metabolically active to light up. Dead bacteria containing luciferase will not generate light, unlike green fluorescent protein (GFP), another reporter used to image bacteria (see this post that describes an experiment with Borrelia burgdorferi expressing GFP).To generate bioluminescent L. interrogans, the researchers hooked the firefly luciferase gene up to a strong L. interrogans promoter and inserted the construct into a transposon carried on a suicide plasmid. The plasmid was then introduced into L. interrogans by conjugation (see this blog post for details of the process). Cultures of the engineered spirochetes lit up when luciferin, the luciferase substrate, was added. The amount of light emitted depended on the culture density: more light was detected at higher culture densities.Mice are ideal models to study persistent infection of the kidney since many rodents are chronic carriers of Leptospira out in nature. These rodents don't get sick from the infection, but they contaminate the environment with the spirochete every time they urinate.To see how chronic infection is established, the investigators injected a sublethal dose of 107 bioluminescent L. interrogans cells into the abdominal cavity of C57BL6/J mice and took sequential images of the animals over the following months. Albino mice were used because dark fur blocks the signal emitted by the bioluminescent bacteria. (They later showed that standard C57BL6/J mice with black fur could be used as long as they shaved the fur off before placing them in the imager.) The mice were injected with luciferin 10 minutes prior to imaging. There turned out to be two phases of infection (see the "MFlum1" plot in the graph below). In the acute phase, the bioluminescent signal rose to a peak by day 4 and quickly declined to background levels by day 7. The signal then started increasing again slowly and plateaued after a month.Figure 2A from Ratet et al., 2014. Images of a single mouse taken sequentially are shown below the graph. Click for larger image. Source.Images of a single mouse taken at different times after inoculation are shown below the graph. Thirty minutes after inoculation, signal was detected in the abdominal cavity. By day 3, the signal consumed the entire mouse. At this point, the bacteria were probably circulating in the bloodstream. By day 6, the signal was almost completely gone. After day 6, the signal appeared again, but it was confined to the kidneys. The intensity of the signal in the kidneys increased with time. They did not detect signal anywhere else in the animals during the second phase. They even sacrificed some of the infected mice 2 months into the infection to check the organs directly, but they failed to detect Leptospira by bioluminescence and qPCR in the brain, lungs, spleen, liver, or blood. Not surprisingly, bioluminescence was detected in urine, confirming that the mice were shedding live L. interrogans.Next, the investigators tested the effectiveness of antibiotics in treating mice infected with the bioluminescent L. interrogans. Several antibiotics are used to treat acute leptospirosis in humans, including penicillin and azithromycin. It is generally believed that antibiotics are more effective if provided early in acute illness. Therefore, the investigators tested whether the timing of antibiotic treatment was important for effectiveness.As expected, penicillin treatment was most effective when treatment was started at the beginning of the acute phase. In mice treated with daily injections of penicillin for 5 days starting a day after infection, no bioluminescence was detected in the kidneys, and urine was free of L. interrogans as measured by qPCR. However, if treatment was delayed until three days after inoculation, during the peak of acute infection, a low level of L. interrogans was detected in urine by qPCR even though no bioluminescence was detected in the kidneys. It is likely L. interrogans was present in the kidneys but at levels too low to be detected by the imager. The bioluminescence approach clearly does not have the sensitivity of qPCR. Additional experiments revealed that the limit of detection was 100 bioluminescent L. interrogans cells in 100 μl of buffer.Penicillin was even less effective when administered after the spirochetes settled in the kidneys. When penicillin treatment was initiated at peak bacterial load in the kidneys, day 25 of infection, the signal diminished by over 90% but then bounced back to the level observed before treatment began (see figure below). Ciprofloxacin also failed to eradicate the bacteria.Figure 5A from Ratet et al., 2014. Antibiotics were administered for 5 days started on day 25 of infection. Cipr, ciprofloxacin; Pen, penicillin. Source.On the other hand, azithromycin managed to knock the signal in the kidneys down to background levels (see graph below). However, the signal came back within a week, although not to the high levels seen in untreated mice. A second course of antibiotics starting on day 112 knocked the signal back down to near background levels, but again, spirochete numbers rebounded, although not to the levels seen before retreatment.Figure 5B from Ratet et al., 2014. Azithromycin was administered for 5 days starting on day 25 and day 112 of infection. Source.Why are antibiotics ineffective in eradicating L. interrogans during the chronic phase? Like other bacteria, L. interrogans can form biofilms in vitro. Scientists who work with Leptospira believe that they also assemble into biofilms within the kidney tubules during chronic infection. Biofilms are hard to eliminate in part because they harbor persister cells that tolerate antibiotics. (See this post for some background on persister cells.)I should caution readers from concluding that tolerance accounts for the poor effectiveness of antibiotics in treating human cases of acute leptospiro... Read more »
Ratet G, Veyrier FJ, Fanton d'Andon M, Kammerscheit X, Nicola MA, Picardeau M, Boneca IG, & Werts C. (2014) Live imaging of bioluminescent Leptospira interrogans in mice reveals renal colonization as a stealth escape from the blood defenses and antibiotics. PLoS Neglected Tropical Diseases, 8(12). PMID: 25474719
Goris MG, Kikken V, Straetemans M, Alba S, Goeijenbier M, van Gorp EC, Boer KR, Wagenaar JF, & Hartskeerl RA. (2013) Towards the burden of human leptospirosis: duration of acute illness and occurrence of post-leptospirosis symptoms of patients in the Netherlands. PloS One, 8(10). PMID: 24098528
Fanton d'Andon M, Quellard N, Fernandez B, Ratet G, Lacroix-Lamandé S, Vandewalle A, Boneca IG, Goujon JM, & Werts C. (2014) Leptospira Interrogans induces fibrosis in the mouse kidney through Inos-dependent, TLR- and NLR-independent signaling pathways. PLoS Neglected Tropical Diseases, 8(1). PMID: 24498450
Researchers at Case Western Reserve University and the University of Michigan have produced the first image of an important human protein as it binds with ribonucleic acid (RNA), a discovery that could offer clues to how some viruses, including HIV, control expression of their genetic material. That information could lead to new strategies to block viruses from replicating, thereby limiting or halting infection.... Read more »
Morgan, C., Meagher, J., Levengood, J., Delproposto, J., Rollins, C., Stuckey, J., & Tolbert, B. (2015) The First Crystal Structure of the UP1 Domain of hnRNP A1 Bound to RNA Reveals a New Look for an Old RNA Binding Protein. Journal of Molecular Biology, 427(20), 3241-3257. DOI: 10.1016/j.jmb.2015.05.009
We all have our standards. For humans, it's the five-second rule. For macaques, it's "think twice before eating food off a pile of poop." The monkeys have several ways of keeping their food (sort of) clean. And the most fastidious macaques, it seems, are rewarded with fewer parasites.
On the Japanese island of Koshima, scientists have been studying Japanese macaques (Macaca fuscata) for nearly seven decades. The tiny, forested island is overrun with the monkeys, which live there naturally... Read more »
Sarabian C, & MacIntosh AJ. (2015) Hygienic tendencies correlate with low geohelminth infection in free-ranging macaques. Biology letters, 11(11). PMID: 26538539
This week’s video tip is longer than usual. But if you want to dig deeper into all the data that you know is coming in to the UCSC Genome Browser, you want to use the Table Browser. If you’ve only used the genome browser interface, you are missing a lot of opportunity to mine for […]... Read more »
Rosenbloom, K., Armstrong, J., Barber, G., Casper, J., Clawson, H., Diekhans, M., Dreszer, T., Fujita, P., Guruvadoo, L., Haeussler, M.... (2014) The UCSC Genome Browser database: 2015 update. Nucleic Acids Research, 43(D1). DOI: 10.1093/nar/gku1177
Mangan ME, Williams JM, Kuhn RM, & Lathe WC. (2014) The UCSC Genome Browser: What Every Molecular Biologist Should Know. Current Protocols in Molecular Biology., 107(19.9), 199-199. DOI: 10.1002/0471142727.mb1909s107
As you grab your rake or leaf-blower this fall, you might wonder how it is possible for trees to make so many leaves. Learn where they all came from.... Read more »
Pijpers, J., Winkler, M., Surendranath, Y., Buonassisi, T., & Nocera, D. (2011) Light-induced water oxidation at silicon electrodes functionalized with a cobalt oxygen-evolving catalyst. Proceedings of the National Academy of Sciences, 108(25), 10056-10061. DOI: 10.1073/pnas.1106545108
E. fishelsoni s a bacterium that breaks the rules. It grows from 10 µm long to a fully visible 0.7 mm….in twelve hours! Normally, diffusion isn’t adequate for a bacterium this big because it takes too long for two interacting proteins to find one another. But what if the bacterium make more of the protein, so much more that it can find a partner all the time. How can you make that much of each protein? E. fishelsoni does it by making 85,000 copies of its genome….. every single day!... Read more »
Bresler V, Montgomery WL, Fishelson L, Pollak PE. (1998) Gigantism in a bacterium, Epulopiscium fishelsoni, correlates with complex patterns in arrangement, quantity, and segregation of DNA. J Bacteriol., 180(21), 5061-5611. info:/9791108
"Immune clue to preventing schizophrenia" went the BBC headline, as the paper by Peter Bloomfield and colleagues  garnered some significant media interest recently specifically tied into their findings suggesting that: "neuroinflammation is linked to the risk of psychosis and related disorders, as well as the expression of subclinical symptoms."Based on the use of "second-generation radioligand [11C]PBR28 and PET to image microglial activity in the brains of participants at ultra high risk for psychosis", researchers reported on 56 participants looking to record their microglial activity. Microglia, as I've talked about before, are something like the constant gardeners of our immune defences in their role as macrophages (big eaters of the immune system) of the brain and spinal cord. Bloomfield et al reported that some of the highest levels of microglia activity were seen in those participants diagnosed with schizophrenia. There also appeared to be something of a potentially important dose related relationship between microglial activity and those at ultra-high risk of psychosis too. Ergo: "Microglial activity is elevated in patients with schizophrenia and in persons with subclinical symptoms who are at ultra high risk of psychosis and is related to at-risk symptom severity." Quite a nice write-up of the study can be read here.It's not necessarily new news that immune activation and inflammatory processes may be part and parcel of at least some schizophrenia. I've covered the topic quite a few times on this blog (see here and see here for example). The novelty in the Bloomfield results is that researchers actually looked at neuroinflammation as being part of the process linked to excess immune activation in their cohort including people on the schizophrenia-psychosis spectrum.Where next with this work? Well, replication - independent replication - is a must-have for this area and might also include some analysis of other more general circulating markers of inflammation such as C-reactive protein (CRP) and other pentraxins for example. That also the orchestra of immune-related chemicals that fall under the banner of cytokines (see here) might also be included in further work would also be a valuable scientific addition bearing in mind that not all schizophrenia/psychosis might be immune related: remember the schizophrenias (plural). I might also forward the idea that we might already have some clues as to the possible agents involved in such immune stimulation as per the interesting work looking at Toxoplasma gondii and some schizophrenia (see here).With regards to the BBC and other media talking about possible treatments focused on some 'anti-inflammatory' action, this again is not new news as per reports such as the one by Friedrich . With other psychiatric labels in mind also talking about inflammation as being part and parcel of pathology (see here) there may be a variety of anti-inflammatory strategies requiring scientific analysis within the context of schizophrenia and/or psychosis. Indeed, such work might overlap across various different labels (see here) and even point to some rather unorthodox intervention ideas (see here and see here).The times are a changin' for psychiatry methinks.Music: All I Wanna Do Is Have Some Fun...---------- Bloomfield PS. et al. Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [11C]PBR28 PET Brain Imaging Study. American Journal of Psychiatry. 2015. Oct 16. Friedrich MJ. Research on Psychiatric Disorders Targets Inflammation. JAMA. 2014; 312: 474-476.----------Bloomfield, P., Selvaraj, S., Veronese, M., Rizzo, G., Bertoldo, A., Owen, D., Bloomfield, M., Bonoldi, I., Kalk, N., Turkheimer, F., McGuire, P., de Paola, V., & Howes, O. (2015). Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [ C]PBR28 PET Brain Imaging Study American Journal of Psychiatry DOI: 10.1176/appi.ajp.2015.14101358... Read more »
Bloomfield, P., Selvaraj, S., Veronese, M., Rizzo, G., Bertoldo, A., Owen, D., Bloomfield, M., Bonoldi, I., Kalk, N., Turkheimer, F.... (2015) Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [ C]PBR28 PET Brain Imaging Study . American Journal of Psychiatry. DOI: 10.1176/appi.ajp.2015.14101358
An overview of my PhD so far...... Read more »
Ottenburghs, J., Ydenberg, R., Van Hooft, P., Van Wieren, S., & Prins, H. (2015) The Avian Hybrids Project: gathering the scientific literature on avian hybridization. Ibis, 157(4), 892-894. DOI: 10.1111/ibi.12285
A new cholesterol-lowering vaccine leads to reductions in ‘bad’ LDL cholesterol in mice and macaques, according to research. The authors of the study, from the University of New Mexico and the National Institutes of health in the United States, say the vaccine has the potential to be a more powerful treatment than statins alone.... Read more »
Crossey, E., Amar, M., Sampson, M., Peabody, J., Schiller, J., Chackerian, B., & Remaley, A. (2015) A cholesterol-lowering VLP vaccine that targets PCSK9. Vaccine, 33(43), 5747-5755. DOI: 10.1016/j.vaccine.2015.09.044
A dozen or so solitary trees scattered within a remote part of northeastern Madagascar are all that remains of Voanioala gerardii in its natural setting.In Malagasy, the national language of the large African island, the plant is called voanio-ala. This translates to 'forest coconut', which is appropriate given that the coconut (Cocos nucifera) is one of its closer relatives. Incidentally, the genus names assigned to several other palm trees found on Madagascar (e.g. Marojejya and Raphia) were also derived from the Malagasy language.The species is named for Gerard Jean, who collected the tree fragments that sparked the interest of John Dransfield, a palm researcher at Kew. Dransfield came over from the UK to investigate the tree and subsequently named and described it in a scientific publication.Like the coconut, V. gerardii grows as a tall tree (15-20 m high, compared to the 30 m maximum height attained by coconut trees) with a bare trunk and a bunch of long leaves (~5 m in length) at the very top. Both trees are harvested for their palm hearts (the scrumptious inner core of the stems of young trees) and large edible fruit (which grow in clusters).While coconuts naturally occur on beaches (spreading via the ocean due to their buoyant fruit), V. gerardii tends to grow inland (thus being called the forest coconut).It's been suggested that its seeds, which currently pile up under mature trees, were once dispersed by now extinct birds or mammals who were large enough to carry them around. This helps to explain why the tree hasn't spread elsewhere and is going extinct (habitat loss and being eaten by humans aren't helping much either).DNA-filled nuclei of (a) Voanioala gerardii and (b) an onion (Source)Among monocots, V. gerardii has the highest known number of chromosomes, with each of its cells containing close to 600 of the DNA threads. This large number is due to many instances over the evolutionary history of the plant where its existing set of chromosomes (i.e. its genome) underwent duplication. Cells of the plant also contain a relatively large amount of DNA, as shown in the above image.ReferencesDransfield J. 1989. Voanioala (Arecoideae: Cocoeae: Butiinae), a new palm genus from Madagascar. Kew Bulletin 44(2):191-198. [First page]Dransfield J. 1992. Voanioala, the forest coconut. Principes 36(3):124-127. [Full text]Johnson MAT, Kenton AY, Bennett MD, Brandham PE. 1989. Voanioala gerardii has the highest known chromosome number in the monocotyledons. Genome 32(2):328-333. [Full text]http://www.arkive.org/forest-coconut/voanioala-gerardii/http://www.palmpedia.net/wiki/Voanioala_gerardii... Read more »
Dransfield J. (1989) Voanioala (Arecoideae: Cocoeae: Butiinae), a new palm genus from Madagascar. Kew Bulletin, 44(2), 191. DOI: 10.2307/4110796
"Psychiatric comorbidities in children with autism spectrum disorder (ASD) are rather a rule than an exception."That was the opening sentence to the paper by Verheij and colleagues  (open-access available here) who charted the stability of such comorbidity in a "7-year follow-up of 74 6-12 year old children with Pervasive Developmental Disorder-Not Otherwise Specified [PDD-NOS]."Continuing a theme from this research group  looking longitudinally at what happened to individuals who "were initially referred for diagnostic evaluation to the Department of Child and Adolescent Psychiatry/Psychology of the Erasmus Medical Center—Sophia Children’s Hospital between July 2002 and September 2004", researchers examined various comorbid psychiatric disorders such as anxiety and mood disorder(s) via the use of the Diagnostic Interview Schedule for Children IV Parent Version (DISC-IV-P) over the course of two testing waves (aged 6-12 years and aged 12-20 years).They found that: "The rate of comorbid psychiatric disorders dropped significantly from childhood (81 %) to adolescence (61 %)." Specifically, the frequency of anxiety disorders dropped from 55% in wave 1 (6-12 years) to 31% in wave 2 (12-20 years) (based on an average follow-up time between waves of nearly 7 years). The frequency of social phobia also seemed to drop between the testing waves (~11% vs. 1%) as did the frequency of specific phobias (40% vs. 25%); these differences were noted to be significant.But it was not all good news, as we are told that: "The rates for externalizing (i.e. disruptive) disorders did not significantly change from childhood (i.e. 61 %) to adolescence (i.e. 51 %)"; this categorisation including diagnoses such as attention-deficit hyperactivity disorder (ADHD) (various types) and conduct disorder. Indeed also, when it came to issues such as major depressive disorder, the authors noted a non-significant increase in the frequency of this label examined over the course of the testing waves. Further: "Of the individuals who had no comorbid psychiatric disorder in childhood (n = 14), 50 % (n = 7) stayed free of a comorbid psychiatric disorder in adolescence, whereas 50 % (n = 7) of the individuals developed at least one comorbid psychiatric disorder in adolescence."In terms of predicting stability across the comorbidity and non-comorbidity groups - "the “persistent presence” group (n = 38) versus the “presence to absence” group (n = 22)" - parent-reported stereotyped behaviours and reduced social interest in childhood as measured on the Children’s Social Behavior Questionnaire (CSBQ) seemed to play something of a role, albeit with the requirement for much further study.Set within the context of PDD-NOS falling into at least some descriptions of the autism spectrum (newer diagnostic criteria don't mention this category) these are interesting results. That certain psychiatric comorbidity wax and wane as a function of issues such as maturation for example, provides something of a ray of hope that these often disabling comorbidity (yes, anxiety can be utterly disabling) may not always be set in stone. At least that is, with regards to their reaching clinical significance and diagnostic thresholds.Following a trend in autism research suggesting that the core traits of autism are also probably more dynamic than anyone has hitherto appreciated (see here), I might also advance the idea that where issues such as anxiety wane, so to this might have an effect on the core presentation of autism in terms of things like intervention success for example (see here). I might also refer you back to the idea of optimal outcome (OO) in relation to autism and what this might also mean for the presence of psychiatric comorbidity (see here).The suggestion that certain psychiatric elements however may not be as likely to retreat when it comes to some autism, such as certain types of ADHD and/or major depressive disorder, remains a worrying prospect. As per the Myriam De-la-Iglesia / José-Sixto Olivar discussion piece  (see here for my take) on depression and at least some autism, the often far-reaching effects of depression in conjunction with autism is something that really does need to be tackled, and tackled effectively. Not least because of the "high index of depression in this collective emphasises the need to detect suicidal tendencies." A sad but all too real outcome I'm afraid (see here).I end with a few caveats to bear in mind about the Verheij data: "Results are based on parental interviews in a relatively small sample of individuals with PDD-NOS with an average to high IQ who were referred to one particular center, thus clinicians should make careful considerations regarding their own specific clients, and further research on samples with more phenotypic variation in ASD severity and cognitive ability using multiple informants is needed." That also there were gaps in important variables such as medication history and other more socially-related variables should also be noted.Still, this kind of longitudinal research is the kinda thing that autism science really needs to do a lot more of, allied to the idea that psychiatric comorbidity is probably over-represented when it comes to the label of autism .To close, the Japanese trailer for the next Star Wars instalment has some new scenes to tantalise...---------- Verheij C. et al. The Stability of Comorbid Psychiatric Disorders: A 7 Year Follow Up of Children with Pervasive Developmental Disorder-Not Otherwise Specified. J Autism Dev Disord. 2015 Oct 12. Louwerse A. et al. ASD Symptom Severity in Adolescence of Individuals Diagnosed with PDD-NOS in Childhood: Stability and the Relation with Psychiatric Comorbidity and Societal Participation. J Autism Dev Disord. 2015 Sep 22. De-la-Iglesia M. & Olivar JS. Risk Factors for Depression in Children and Adolescents with High Functioning Autism Spectrum Disorders. ScientificWorldJournal. 2015;2015:127853. Russell AJ. et al. The mental health of individuals referred for assessment of autism spectrum disorder in adulthood: A clinic report. Autism. 2015 Oct 15. pii: 1362361315604271.----------... Read more »
Verheij C, Louwerse A, van der Ende J, Eussen ML, Van Gool AR, Verheij F, Verhulst FC, & Greaves-Lord K. (2015) The Stability of Comorbid Psychiatric Disorders: A 7 Year Follow Up of Children with Pervasive Developmental Disorder-Not Otherwise Specified. Journal of autism and developmental disorders. PMID: 26456972
New research shows that drinking one 16-ounce energy drink can increase blood pressure and stress hormone responses significantly. This raises the concern that these response changes could increase the risk of cardiovascular events.... Read more »
Svatikova, A., Covassin, N., Somers, K., Somers, K., Soucek, F., Kara, T., & Bukartyk, J. (2015) A Randomized Trial of Cardiovascular Responses to Energy Drink Consumption in Healthy Adults. JAMA, 1. DOI: 10.1001/jama.2015.13744
Copper and silver have a lot in common. Unlike most metals, they occasionally occur on their own (i.e. in a native metallic form) in nature. This easy access meant they were among the first metals we used to make stuff. Being easy to work, fairly resilient, and nice to look at, they've been shaped into decorative items, coins, and musical instruments. Both metals are great at conducting electricity and can readily be stretched into wires. During WWII, the extensive use of copper in the paraphernalia of war led to its replacement by silver in a couple of key manufacturing systems back at home. In particular, silver was used in place of copper to wire up aluminum smelters and to construct electromagnets for enriching uranium (as part of the Manhattan Project).Native copper with silver crystals (Source)Another commonality between copper and silver is their ability to kill bacteria and fungi. Pretty much every ancient civilization used the metals as a means of controlling microbial growth, usually for the purposes of preventing or treating infections.In the late 19th century, doctors began applying drops of dilute silver nitrate solutions to the eyes of very recently born babies. This was done to prevent infections, particularly conjunctivitis due to Chlamydia trachomatis or Neisseria gonorrhoea being transmitted from infected mothers to their offspring during birth. The prophylactic use of silver nitrate in newborns remains in practice in many countries. Silver nitrate (solution) and silver sulfadiazine (cream) are applied to burns and other skin wounds to prevent infections. Similarly, silver-based textiles (e.g. silver-coated nylon) are used to dress burns and large open wounds. Medical devices that are stuck inside people (e.g. catheters, endotracheal tubes, and prosthetic heart valves) can be coated with silver to inhibit their colonization by microbes and thus reduce healthcare-associated infections such as UTIs and pneumonia.During a 1832 cholera outbreak in Paris, it became apparent that copper workers were less likely to be struck down by the bacterial illness. This ushered in the widespread use of copper salts for the treatment of various infections (e.g. impetigo, tuberculosis, and syphilis), which continued into the early 20th century. These days, touch surfaces such as door handles, railings, and bathroom fixtures in hospitals are increasingly being made out of the metal. In the 18th century, folks began treating crop seeds with copper sulfate to inhibit disease-causing fungi that hitch a ride on them (it's a useful way to stay alive between plant generations). Starting in the 19th century, copper-based solutions (e.g. Bordeaux mixture) were widely used in vineyards to control the growth of grape-eating fungi.Cuprum sulfuratum (copper sulfate) was a fixture in the pharmacies of yesterday (Source)Copper and silver can also be put to work disinfecting water, reducing the potential for exposure to harmful microbes via the plethora of uses we seem to have for this weirdo liquid. This is appealing because chlorine, the big cheese of the water disinfection scene, has a couple of problems with it. Chlorine is not a particularly pleasant substance to work with. It can react with bits of organic carbon in water to form harmful chlorinated compounds such as trihalomethanes. It can corrode equipment and is less effective at high temperature or pH. Finally, isn't great at killing certain pathogens like Cryptosporidium or Legionella.It's long been recognized that storing water in a copper or silver vessel makes it safer to drink. The Smith Papyrus, an ancient Egyptian medical text, mentions using copper to disinfect drinking water. Alexander the Great brought along silver containers for storing water during his efforts to conquer the world. Old Ayurvedic medical texts advise keeping water in copper or silver pots. The Aztecs, ancient Greeks, and Romans were also into this disinfection approach. American pioneers making their way west during the late 19th century dropped copper or silver coins in their water barrels to slow the growth of microbes during their travels. During WWII, Japanese soldiers did something similar, placing copper pieces in their water bottles to try and avoid dysentery.In the early 20th century, a sterilization technique was developed based on adding a small amount of silver ions to water by passing an electrical current through a submerged silver anode. Along the same lines, there is evidence that applying a weak current to silver-containing wound dressings can accelerate wound healing.Spacecraft launched by NASA (e.g. Apollo) and the Soviet space program (e.g. Mir) utilized silver ions to purify the water consumed by astronauts during their time in space. This approach is currently being used aboard the International Space Station.Water purification units based on the introduction of microbe-killing copper and/or silver ions are currently used in water distribution systems in homes, hotels, and hospitals. They can also be found cleaning up the water flowing through swimming pools, spas, fountains, and the giant tanks of water we keep aquatic mammals in for our pleasure. Notably, there are concerns with the long-term use of silver-copper ionization systems in hospitals.There's a lot of interest in using copper and silver to disinfect water consumed in developing countries. Having access to safe drinking water is incredibly important. For example, if bacteria such as Salmonella and Vibrio cholerae get into water supplies, they can end up infecting the digestive tracts of those who drink the water, causing diarrhea and other flu-like symptoms. Worldwide, diarrhoeal disease is a substantial cause of death in children. Although there are many methods of disinfecting water, most are relatively expensive and/or not easily acquired (e.g. if you're a farmer living in an isolated rural area). Just as they did thousands of years ago, copper or silver can disinfect water for a household. One technique is to store water in a copper pot overnight. Alternatively, water can be disinfected in under an hour with a device consisting of a copper screen or foil placed inside a glass or plastic bottle. These devices are fairly inexpensive, durable, don't require energy, reusable, and easily maintained.ReferencesBarillo DJ, Marx DE. 2014. Silver in medicine: A brief history BC 335 to present. Burns 40(Suppl 1):S3-S8.... Read more »
Barillo D, & Marx D. (2014) Silver in medicine: A brief history BC 335 to present. Burns. DOI: 10.1016/j.burns.2014.09.009
Borkow G, & Gabbay J. (2009) Copper, an ancient remedy returning to fight microbial, fungal and viral infections. Current Chemical Biology, 3(3), 272-278. DOI: 10.2174/187231309789054887
Different colors and flavors of pig?
pig, micro pig, genetics, gene editing, agriculture, pets
The Chinese genomics institute BGI (Beijing Genomics Institute) has announced that tiny pigs, created through genetic-editing techniques, are now being sold as pets. The profits generated through revenue will be used to further develop research in this area.
Demand for pigs as pets has been growing, especially among the U.S public. Yong Li, director of BGI believes that in the future gene-editing techniques will allow the company to offer pigs with different colors and patterns, he told the Nature journal.... Read more »
Li F, Li Y, Liu H, Zhang H, Liu C, Zhang X, Dou H, Yang W, & Du Y. (2014) [Production of GHR double-allelic knockout Bama pig by TALENs and handmade cloning]. Yi chuan , 36(9), 903-11. PMID: 25252308
I read with interest the paper by Roberto Sacco and colleagues  providing some much needed clarity on the topic of head circumference and brain size in relation to autism spectrum disorder (ASD).Detailing the results of a systematic review and meta-analysis based on "27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls", researchers provided "conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism."So: "Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly." Further: "Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients." Something of an interaction was also reported between age and total brain volume "resulting in larger head circumference and brain size during early childhood."As per previous discussions on this topic, there was always a degree of confusion about the the research reporting abnormal head size to be linked to autism (see here). Previous, quite sweeping generalisations, about 'big heads' being linked to the presentation of autism turned out to be a little too sweeping despite some investigations even talking about head size and screening opportunities (see here). The recognition of specific 'types' of autism perhaps being linked to head size and brain enlargement (see here) perhaps offered a more 'real-world' perspective to this issue in-line with quite a lot of research direction in these days of more 'plural' autism (see here). The evidence for this endophenotype concept related to head size comes in a large part from the various studies of specific genetic issues being associated with autism and head size as per the example from Nebel and colleagues .Being careful not to over-generalise the issue of age related to head size  and understanding that where one draws comparison population norm data from might be important , I'd like to think that there are still some research benefits to continued study of head and brain size when it comes to autism. Not least are the various studies talking about connectivity with reference to brain regions in relation to autism, and whether brain size might be an important factor. That accelerated head circumference might be part and parcel of other growth parameters  is also an interesting observation and begs some interesting questions about [some] autism in relation to whole body physiology...'Everything I do' (but perhaps not the way remember).---------- Sacco R. et al. Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis. Psychiatry Res. 2015 Sep 28. pii: S0925-4927(15)30057-3. Nebel RA. et al. Reciprocal Relationship between Head Size, an Autism Endophenotype, and Gene Dosage at 19p13.12 Points to AKAP8 and AKAP8L. PLoS One. 2015 Jun 15;10(6):e0129270. Cederlund M. et al. Pre-schoolchildren with autism spectrum disorders are rarely macrocephalic: a population study. Res Dev Disabil. 2014 May;35(5):992-8. Raznahan A. et al. Compared to what? Early brain overgrowth in autism and the perils of population norms. Biol Psychiatry. 2013 Oct 15;74(8):563-75. Chawarska K. et al. Early generalized overgrowth in boys with autism. Arch Gen Psychiatry. 2011 Oct;68(10):1021-31.----------Sacco R, Gabriele S, & Persico AM (2015). Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis. Psychiatry research PMID: 26456415... Read more »
Sacco R, Gabriele S, & Persico AM. (2015) Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis. Psychiatry research. PMID: 26456415
Do you write about peer-reviewed research in your blog? Use ResearchBlogging.org to make it easy for your readers — and others from around the world — to find your serious posts about academic research.
If you don't have a blog, you can still use our site to learn about fascinating developments in cutting-edge research from around the world.
Research Blogging is powered by SMG Technology.
To learn more, visit seedmediagroup.com.