Monthly Archives: October 2009

Podcast Review: Nature Neuropod Oct 28th 2009

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In the 28th October edition of the Nature Neuropod, Kerri Smith interviews researchers who have published recent interesting research in the field of neuroscience. In one of the interviews Smith talks with researcher Ted Abel who has identified a cyclic AMP signalling pathway that is modified in the hippocampus during sleep deprivation such that the levels of phosphdiesterase-4, which degrades cAMP are increased. Further when this pathway was blocked, sleep deprivation-related memory impairment was reversed. There may be therapeutic implications pending further research. There is also an interview with Professor Pasko Rakic who has been looking at the evolution of the central nervous system in mammals. There is  a fascinating interview with Eve Marder about individual differences in the central nervous systems of crabs, moving away from the paradigm of averaging group properties. This question of the difference between individual and group properties is an important one which is relevant to many different areas of research in the life sciences including clinical sciences (see for instance the paper reviewed in this article). There is also a look at research on place cells – which code for spatial locations. The slow pace and clearly enunciation work well for the complex material that is carefully explained for the listeners.

 

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Book Review:The Greatest Show on Earth

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The book reviewed here is ‘The Greatest Show on Earth’ by Richard Dawkins. Both Dawkins and his wife actress Lalla Ward narrate the book in an engaging style and in the process convey the awe of nature that permeates the book. Indeed for those unfamiliar with Dawkin’s works – he is a champion of communicating the beautiful and at the same time inexorable logic of evolution while at the same time answering the common criticisms that have been levelled against evolution. In my opinion, Dawkins writing represents the embodiment of rationalism in search of an ephemeral eternal truth about nature which because of the subject of its enquiry takes on a transcendent quality. Dawkin’s latest work references many of his earlier works, reiterating important nuances in evolutionary theory such that it parallels a collection of axiomatic proofs building to a final conclusion. The conclusion in this case is the essence of several billion years of evolution on Earth. Dawkins examines the possible origins of life with a fascinating reference to Darwin’s profound passage on the chemicals in a pond which might contribute to the beginnings of life. He covers artificial, natural and sexual selection and illustrates each of these with elegant examples that reaffirm the concepts. Indeed what it is striking is Dawkin’s ability to effortlessly take such examples which are selected from across vast expanses of time as well as geographically and phylogenetically disparate regions and which reveal a supreme familiarity with the natural world. Indeed it seems that any debate about the underlying principles of evolution should begin with a demonstration on both sides of such familiarity particularly as the significance of the natural world is rarely contested. Dawkins also discusses the gene pool and this part in particular I had found interesting. I had overlooked that the individual and successful genes are part of a gene pool within the organism and this relationship between an individual gene and the remainder of the genome (or genomes if the wider group is considered) adds a necessary layer of complexity. For instance, the small changes in genes which may initially cause problems can be compensated by the actions of other gene products. This is interesting in the light of recent evidence that in people, each generation results in an average of 100 mutations in the genome*. In this regards it was also interesting to note that different parts of the genome have staggeringly different rates of mutational change with such changes being particularly rare in histone-related genes. On further reflection about some of the underlying evolutionary principles, I thought that these might easily be abstracted in mathematical form and this became more evident when Dawkins describes one of the computer programs he had written to simulate evolutionary changes (indeed genetic algorithms have been particularly successful in real world applications). This again testifies to the skills and effectiveness of Dawkins in translating such refined arguments into a format that is easily accessible. He has in the process developed a language which combines the underlying logic of evolution with those additional components of knowledge which reach out to a wider audience**. This is another indispensable work for those with an interest in the wonders of the natural world.

* It is tempting to suppose that multi-gene mutations may produce significant changes in a network effect although such an effect is improbable if such mutations are independent (given the size of the genome)

** It would be interesting to see if such rules could form the basis for an open-source educational and research software paradigm

References

Richard Dawkins. The Greatest Show on Earth. Narrated by Richard Dawkins and Lalla Ward. Random House Audio Books. 2009.

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Blog Review:Doctor Dymphna’s Diliberations

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The blog reviewed here is ‘Doctor Dymphna’s Diliberations‘.

Appearance and Design

The blog has a black background and a slightly off-black background in the central pane on which the white text of the articles is overlaid. The title pane consists of the blog name together with a colourful photo-like design. At the time of writing on the right hand pane there is an ‘About’ section for the blog, links to the associated twitters, blogroll, category cloud, recent posts and links to other websites. The blog can be navigated via an archived index also on the right hand pane. The blog is hosted at WordPress.

Articles

In the first post, there is an explanation of why the blog was started as well. Although there is a suggestion of abandoning anonymity, I couldn’t find a reference to the author’s name although this is apparently identifiable from the related twitter. As I couldn’t find a reference to the same name in the blog, I have refrained from using it in case they’re not equivalent. What I found interesting was that the author uses a combination of mindfulness-based therapy, cognitive-based therapy and pharmacotherapy. Some of the posts broached broader issues which could be argued by some to cross over into other distinct and separate domains. There are also interesting articles such as this on lifestyle approaches based on the research literature. The author also writes about her son’s condition and how this affects her. This article looks at some of the authors reasons for tweeting and indeed it is through the twitter account that I first came across this blog. There are also a number of book and film reviews.

Conclusions

This is a relatively young blog which usually has a few posts every month. The articles are sufficiently long to explore the topic of interest and to present these from the author’s perspective. I found some of the psychotherapeutic posts to be particularly interesting.

Addendum (10.11.09)

The About section has subsequently been updated – the author of the blog is indeed Dr Elizabeth Cordes

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Review: YouTube and ‘Neurological Knowledge’

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The article reviewed here is a short report in the Lancet Neurology by Adrian Burton on the applications of YouTube in neurology with a particular focus on neurodegenerative conditions (Burton, 2008). Burton looks at a few channels on YouTube and provides opinions on the likely success of such channgels with the helpf interviews with relevant figures in the field. Although a number of channels are discussed, two in particular are focused on – the UK Alzheimer’s Society channel and the UCSF Memory and Aging channel. There is a discussion of whether these channels will remain in the ‘background’ in terms of viewings given the competition they face from other videos on the site which include those from television companies as well as viral marketing videos from large companies trying to reach a global audience.

At the time of writing, the Alzheimer’s Society channel has 53 clips uploaded. In this clip for instance, Neil Hunt, Chief Executive of the Alzheimer’s Society talks about Alzheimer’s Disease. At the time of writing the channel also has videos in Urdu, Punjabi, Hindi and Bengali. There are also interviews with people with Alzheimer’s Disease who describe their experiences and discuss some of the stigma that has been associated with the condition as well as educating viewers about misconceptions which contribute to this stigma.

The University of California San Francisco channel contains a number of videos about dementia including one on cognition in dementia, moral reasoning in Frontotemporal Dementia (FTD), FTD and emotions, and in this video Dr Bruce Miller explains how useful YouTube can be in education about dementia.

I had looked at videos on vascular dementia on YouTube in this post and concluded at that point that it required a lot of searching to find a few videos that were useful (which of course depends on the purpose of the video and the needs of the audience). However it is only a matter of time before this becomes a very useful medium. There are a number of reasons why I would expect this to become a more important medium for education purposes. Firstly it is not unreasonable to assume that the number of videos on YouTube will continue to increase. If a static proportion of these videos comprises useful educational material then such an increase would be expected in such educational material also. Secondly indexing methods may be expected to improve, be this within the YouTube site itself or through external sites which index some of the useful material in YouTube. The assumption here is that the videos will remain on YouTube indefinitely. Thirdly the methods for video production within the general population may be expected to improve with time as more sophisticated technology becomes available to the general population thus facilitating communication. Fourthly the proportion of the population (globally) with internet access will be expected to increase with time and assuming that a certain proportion of this population contributes videos to YouTube this would again be expected to increase the amount of educational material available (which ties in with the first point) but may also improve the drive for video production as there should be a larger potential audience for this material.

The article is a useful starting point for discussion around this topic and it will be interesting to see developments even within the next year in this field.

References

Burton A. YouTub-ing Your Way to Neurological Knowledge. Lancet Neurology. Vol 7. December 2008. pp1086-1087.

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Review:Implicit and Explicit Aspects of Sequence Learning in Presymptomatic Huntington’s Disease

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The article reviewed here is ‘Implicit and Explicit Aspects of Sequence Learning in Presymptomatic Huntington’s Disease’ by Ghilardi and colleagues and freely available here. In the abstract, the authors conclude

These results suggest that both explicit and implicit aspects of sequence learning may be impaired before the onset of motor symptoms. However, when attentional demands decrease, explicit, but not implicit, learning may improve

Thus the authors compare and contrast implict and explicit learning in Huntington’s Disease (HD) for a very specific task. The study revolves around a sequencing task and some assumptions. The assumptions are that in this case, implicit and explicit learning can be demarcated according to different elements of the response to the task. Thus for instance they argue that as learning proceeds, the movements become more efficient, saving energy and that this occurs implicitly. They also argue that the number of anticipatory movements in the task is a proxy for explicit learning. However it could be argued that there can be an overlap. Thus the subject could tire of the movements involved in the task and consciously seek to perform these actions more efficiently. Further these actions could be accompanied by an internal dialogue which could almost certainly be considered an explicit form of learning or it could occur non-verbally where the subject nevertheless attends to this goal. Similarly for the initial period of learning the task involves consideration of the sequence of events but here too it could be asked ‘does the learning take place consciously’ (the same could, I think, be asked of this example where the question could be asked  ‘is this chimp consciously or explicitly aware of what he is doing?’). In effect then, it might be reasonable to ask if implicit or explict learning are continuous rather than discrete functions or even if this characterisation is task specific such that it might not be possible to generalise from single tasks.

The researchers have considered a large number of variables which are given in tables 2 and 3. Interestingly they mention that there is a ‘post-hoc analysis’ and a null hypothesis is not clearly stated although the authors do discuss their interpretation of the different components of the task response. The researchers have corrected for the multiple comparisons by using Bonferrini corrections. On the tasks, the subjects with presymptomatic HD (the number of CAG repeats averaged 41. The greater the number the greater is the risk of conversion) performed significantly worse on the implicit and explicit learning components of the tasks as interpreted by the researchers. My initial impression was that the explicit task involved sequencing and might under Baddeley’s model of working memory be attributed to the central executive. There would be expected to be executive dysfunction if the frontal-subcortical loops are affected by the disease process which is seen in HD. The only question here is whether or not there is interruption of the frontal-subcortical loops as this is prefmanifest HD. The researchers also found that if they reduced the complexity of the task there was no significant difference between the premanifest HD subjects and the controls on the ‘explicit learning’ but there was a significant difference on the ‘implicit learning’ task.

The researchers discuss their results and comment on the possible involvement of the dorsolateral prefrontal cortex and a number of other pathways. They also suggest that implicit memory involves primary motor cortex and supplementary motor areas but it is also interesting to note that the cerebellum is thought to play a significant role in this type of learning for motor tasks. I would be interested to see a larger replication study with clearly delineated primary outcome measures and a range of tasks examining both implicit and explicit memory.

 

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

Review: Beyond the Brain in Huntington’s Disease

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The paper reviewed here is ‘Beyond the Brain: widespread pathology in Huntington’s Disease’ by van der Burg and colleagues.The article is written by a group from the Swedish Lund Institute Neuronal survival unit and is classed as a ‘personal view’. However there is a small green box towards the end of the article which contains details of the search strategy and selection criteria which thus allows the reader to gain a better understanding of how the article was orginally constructed as well as providing a useful starting point for someone interested in updating the article. The article focuses on non-neuronal aspects of Huntington’s Disease (HD) in keeping with the expression of Huntingtin in such tissues. The article begins with a look at some of the posited functions of the Huntingtin protein which sets the scene for an exploration of non-neuronal manifestations of HD. There is a look at some of the processes that may contribute to weight loss including possible alterations to Insulin processing and adipocytes although much of the work here is in murine models. The potential impact of mutated Huntingtin on gene expression in myocytes, the expression of Huntingtin in cardiac myocytes, possible actions on osteoblasts or osteoclasts and altered immune response are all considered. The authors then return to the question of the cellular basis of these observations before looking at how such a discussion may inform the search for biomarkers and novel therapeutic paradigms. This is a concise review which references 110 papers and thus provides the reader interested in this area with a useful starting point for their investigations.

References

Van der Burg J M M, Bjorkqvist M and Brundin P. Beyond the brain: widespread pathology in Huntington’s Disease. Lancet Neurology. 2009. 8. 765-74.

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News Round-Up:October 2009 4th Edition

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Research In Dementia

The researchers found that gamma-secretase, an enzyme implicated in Alzheimer’s Disease pathology binds to a class of  transmembrane proteins known as tetraspanins  (Wakabayashi et al, 2009) as well as to a number of other proteins. The tetraspanins have a number of different functions within the cell and it will be interesting to see how gamma secretase relates to these functions. There is further coverage here.

News In Brief

Experimental evidence has shown that expression of IL-6 in murine brain can lead to removal of amyloid plaque by microglial cells. There has been significant evidence to suggest a role for inflammation in the disease process and these new findings show that the relationship between inflammation and build up of Amyloid Plaques in the brain is complex. In one study there was found to be an association between plasma levels of ABeta42 and risk of conversion from Mild Cognitive Impairment to Alzheimer’s Disease and it will be useful to see further replication of these findings. Levels of a class of transcription factors NFAT’s (Nuclear Factors of Associated T-Cells) was significantly elevated in the hippocampi of subjects with Mild Cognitive Impairment or Alzheimer’s Disease compared to controls and at least one pathway has been suggested between activation by Amyloid plaques and expression of regulated genes.

A study in the BMJ showed an increase in the number of prescriptions of antidepressants from 1993 to 2004 and this was attributed to the use of long term prescriptions. There is further coverage here. In the Proceedings of the National Academy of Sciences there is a paper on the use of a new genome sequencing technology – whole exome sequencing (which focuses on genes coding for proteins rather than the entire genome sequence) in a case which resulted in a rapid diagnosis and it will be interesting to see further developments in this area.

There is also evidence that neighbouring groups of Chimpanzees approach the same problem in different ways which the researchers have interpreted as cultural differences. Such interpretations may have implications for developing models of human culture.

Blogosphere

Over at Science Life there is coverage of the Neuroscience conference in Chicago which amongst other items reports on a talk by Erik Kandel, the genetics of anxiety and neuroscience in social media. October 19-23rd was Open Access week and over at Beta Science, Morgan Langille writes about the use of an open-access website BioTorrents for sharing data and other resources. Over at Medical News Today there is a look at an association between gamma synuclein and depression. Software Advice has an article on iPhone applications for doctors and medical students.

References

Wakabayashi T, Craessaerts K, Bammens L, Bentahir M, Borgions F, Herdewijn P,Staes A, Timmerman E, Vandekerckhove J, Rubinstein E, Boucheix C, Gevaert K, De Strooper B.Nat Cell Biol. 2009 Oct 18. [Epub ahead of print]. Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomains.

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