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Category Archives: Stell Cell Genetics

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Cai, D., Netzer, W. J., Zhong, M., Lin, Y., Du, G., Frohman, M., Foster, D. A., Sisodia, S. S., Xu, H., Gorelick, F. S., Greengard, P. Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation. Proc. Nat. Acad. Sci. 103: 1941-1946, 2006. [PubMed: 16449386] [Full Text: http://www.pnas.org/cgi/pmidlookup?view=long&pmid=16449386%5D

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Chau, D.-M., Crump, C. J., Villa, J. C., Scheinberg, D. A., Li, Y.-M. Familial Alzheimer disease presenilin-1 mutations alter the active site conformation of gamma-secretase. J. Biol. Chem. 287: 17288-17296, 2012. [PubMed: 22461631] [Full Text: http://www.jbc.org/cgi/pmidlookup?view=long&pmid=22461631%5D

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Cruts, M., van Duijn, C. M., Backhovens, H., Van den Broeck, M., Wehnert, A., Serneels, S., Sherrington, R., Hutton, M., Hardy, J., St George-Hyslop, P. H., Hofman, A., Van Broeckhoven, C. Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum. Molec. Genet. 7: 43-51, 1998. [PubMed: 9384602]

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De Jonghe, C., Cruts, M., Rogaeva, E. A., Tysoe, C., Singleton, A., Vanderstichele, H., Meschino, W., Dermaut, B., Vanderhoeven, I., Backhovens, H., Vanmechelen, E., Morris, C. M., Hardy, J., Rubinsztein, D. C., St George-Hyslop, P. H., Van Broeckhoven, C. Aberrant splicing in the presenilin-1 intron 4 mutation causes presenile Alzheimer's disease by increased A-beta-42 secretion. Hum. Molec. Genet. 8: 1529-1540, 1999. [PubMed: 10401002]

De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., Goate, A., Kopan, R. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398: 518-522, 1999. [PubMed: 10206645] [Full Text: https://doi.org/10.1038/19083%5D

De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K., Van Leuven, F. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391: 387-390, 1998. [PubMed: 9450754] [Full Text: https://doi.org/10.1038/34910%5D

De Strooper, B. Aph-1, Pen-2, and nicastrin with presenilin generate an active gamma-secretase complex. Neuron 38: 9-12, 2003. [PubMed: 12691659] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0896627303002058%5D

Dermaut, B., Cruts, M., Slooter, A. J. C., Van Gestel, S., De Jonghe, C., Vanderstichele, H., Vanmechelen, E., Breteler, M. M., Hofman, A., van Duijn, C. M., Van Broeckhoven, C. The glu318-to-gly substitution in presenilin 1 is not causally related to Alzheimer disease. (Letter) Am. J. Hum. Genet. 64: 290-292, 1999. [PubMed: 9915968] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)61682-6%5D

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Devi, G., Fotiou, A., Jyrinji, D., Tycko, B., DeArmand, S., Rogaeva, E., Song, Y.-Q., Medieros, H., Liang, Y., Orlacchio, A., Williamson, J., St George-Hyslop, P., Mayeux, R. Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease. Arch. Neurol. 57: 1454-1457, 2000. [PubMed: 11030797] [Full Text: https://jamanetwork.com/journals/jamaneurology/fullarticle/vol/57/pg/1454%5D

Dineley, K. T., Xia, X., Bui, D., Sweatt, J. D., Zheng, H. Accelerated plaque accumulation, associative learning deficits, and up-regulation of alpha-7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins. J. Biol. Chem. 277: 22768-22780, 2002. [PubMed: 11912199] [Full Text: http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11912199%5D

Dolzhanskaya, N., Gonzalez, M. A., Sperziani, F., Stefl, S., Messing, J., Wen, G. Y., Alexov, E., Zuchner, S., Velinov, M. A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very early onset and unusually fast progressing dementia as well as lysosomal inclusions typically seen in Kufs disease. J. Alzheimers Dis. 39: 23-27, 2014. [PubMed: 24121961] [Full Text: https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-131340%5D

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The potential therapeutic benefits of HESC research provide strong grounds in favor of the research. If looked at from a strictly consequentialist perspective, its almost certainly the case that the potential health benefits from the research outweigh the loss of embryos involved and whatever suffering results from that loss for persons who want to protect embryos. However, most of those who oppose the research argue that the constraints against killing innocent persons to promote social utility apply to human embryos. Thus, as long as we accept non-consequentialist constraints on killing persons, those supporting HESC research must respond to the claim that those constraints apply to human embryos.

In its most basic form, the central argument supporting the claim that it is unethical to destroy human embryos goes as follows: It is morally impermissible to intentionally kill innocent human beings; the human embryo is an innocent human being; therefore it is morally impermissible to intentionally kill the human embryo. It is worth noting that this argument, if sound, would not suffice to show that all or even most HESC research is impermissible, since most investigators engaged in HESC research do not participate in the derivation of HESCs but instead use cell lines that researchers who performed the derivation have made available. To show that researchers who use but do not derive HESCs participate in an immoral activity, one would further need to establish their complicity in the destruction of embryos. We will consider this issue in section 2. But for the moment, let us address the argument that it is unethical to destroy human embryos.

A premise of the argument against killing embryos is that human embryos are human beings. The issue of when a human being begins to exist is, however, a contested one. The standard view of those who oppose HESC research is that a human being begins to exist with the emergence of the one-cell zygote at fertilization. At this stage, human embryos are said to be whole living member[s] of the species homo sapiens [which] possess the epigenetic primordia for self-directed growth into adulthood, with their determinateness and identity fully intact (George & Gomez-Lobo 2002, 258). This view is sometimes challenged on the grounds that monozygotic twinning is possible until around days 1415 of an embryos development (Smith & Brogaard 2003). An individual who is an identical twin cannot be numerically identical to the one-cell zygote, since both twins bear the same relationship to the zygote, and numerical identity must satisfy transitivity. That is, if the zygote, A, divides into two genetically identical cell groups that give rise to identical twins B and C, B and C cannot be the same individual as A because they are not numerically identical with each other. This shows that not all persons can correctly assert that they began their life as a zygote. However, it does not follow that the zygote is not a human being, or that it has not individuated. This would follow only if one held that a condition of an entitys status as an individual human being is that it be impossible for it to cease to exist by dividing into two or more entities. But this seems implausible. Consider cases in which we imagine adult humans undergoing fission (for example, along the lines of Parfits thought experiments, where each half of the brain is implanted into a different body) (Parfit 1984). The prospect of our going out of existence through fission does not pose a threat to our current status as distinct human persons. Likewise, one might argue, the fact that a zygote may divide does not create problems for the view that the zygote is a distinct human being.

There are, however, other grounds on which some have sought to reject that the early human embryo is a human being. According to one view, the cells that comprise the early embryo are a bundle of homogeneous cells that exist in the same membrane but do not form a human organism because the cells do not function in a coordinated way to regulate and preserve a single life (Smith & Brogaard 2003, McMahan 2002). While each of the cells is alive, they only become parts of a human organism when there is substantial cell differentiation and coordination, which occurs around day-16 after fertilization. Thus, on this account, disaggregating the cells of the 5-day embryo to derive HESCs does not entail the destruction of a human being.

This account is subject to dispute on empirical grounds. That there is some intercellular coordination in the zygote is revealed by the fact that the development of the early embryo requires that some cells become part of the trophoblast while others become part of the inner cell mass. Without some coordination between the cells, there would be nothing to prevent all cells from differentiating in the same direction (Damschen, Gomez-Lobo and Schonecker 2006). The question remains, though, whether this degree of cellular interaction is sufficient to render the early human embryo a human being. Just how much intercellular coordination must exist for a group of cells to constitute a human organism cannot be resolved by scientific facts about the embryo, but is instead an open metaphysical question (McMahan 2007a).

Suppose that the 5-day human embryo is a human being. On the standard argument against HESC research, membership in the species Homo sapiens confers on the embryo a right not to be killed. This view is grounded in the assumption that human beings have the same moral status (at least with respect to possessing this right) at all stages of their lives.

Some accept that the human embryo is a human being but argue that the human embryo does not have the moral status requisite for a right to life. There is reason to think that species membership is not the property that determines a beings moral status. We have all been presented with the relevant thought experiments, courtesy of Disney, Orwell, Kafka, and countless science fiction works. The results seem clear: we regard mice, pigs, insects, aliens, and so on, as having the moral status of persons in those possible worlds in which they exhibit the psychological and cognitive traits that we normally associate with mature human beings. This suggests that it is some higher-order mental capacity (or capacities) that grounds the right to life. While there is no consensus about the capacities that are necessary for the right to life, some of the capacities that have been proposed include reasoning, self-awareness, and agency (Kuhse & Singer 1992, Tooley 1983, Warren 1973).

The main difficulty for those who appeal to such mental capacities as the touchstone for the right to life is that early human infants lack these capacities, and do so to a greater degree than many of the nonhuman animals that most deem it acceptable to kill (Marquis 2002). This presents a challenge for those who hold that the non-consequentialist constraints on killing human children and adults apply to early human infants. Some reject that these constraints apply to infants, and allow that there may be circumstances where it is permissible to sacrifice infants for the greater good (McMahan 2007b). Others argue that, while infants do not have the intrinsic properties that ground a right to life, we should nonetheless treat them as if they have a right to life in order to promote love and concern towards them, as these attitudes have good consequences for the persons they will become (Benn 1973, Strong 1997).

Some claim that we can reconcile the ascription of a right to life to all humans with the view that higher order mental capacities ground the right to life by distinguishing between two senses of mental capacities: immediately exercisable capacities and basic natural capacities. (George and Gomez-Lobo 2002, 260). According to this view, an individuals immediately exercisable capacity for higher mental functions is the actualization of natural capacities for higher mental functions that exist at the embryonic stage of life. Human embryos have a rational nature, but that nature is not fully realized until individuals are able to exercise their capacity to reason. The difference between these types of capacity is said to be a difference between degrees of development along a continuum. There is merely a quantitative difference between the mental capacities of embryos, fetuses, infants, children, and adults (as well as among infants, children, and adults). And this difference, so the argument runs, cannot justify treating some of these individuals with moral respect while denying it to others.

Given that a human embryo cannot reason at all, the claim that it has a rational nature has struck some as tantamount to asserting that it has the potential to become an individual that can engage in reasoning (Sagan & Singer 2007). But an entitys having this potential does not logically entail that it has the same status as beings that have realized some or all of their potential (Feinberg 1986). Moreover, with the advent of cloning technologies, the range of entities that we can now identify as potential persons arguably creates problems for those who place great moral weight on the embryos potential. A single somatic cell or HESC can in principle (though not yet in practice) develop into a mature human being under the right conditionsthat is, where the cells nucleus is transferred into an enucleated egg, the new egg is electrically stimulated to create an embryo, and the embryo is transferred to a womans uterus and brought to term. If the basis for protecting embryos is that they have the potential to become reasoning beings, then, some argue, we have reason to ascribe a high moral status to the trillions of cells that share this potential and to assist as many of these cells as we reasonably can to realize their potential (Sagan & Singer 2007, Savulescu 1999). Because this is a stance that we can expect nearly everyone to reject, its not clear that opponents of HESC research can effectively ground their position in the human embryos potential.

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Prof. Brian Catchpole – Our People – About – Royal …

Posted: March 14, 2019 at 10:43 am

Brians research interests centre around canine immunology and immunogenetics in relation to susceptibility to immune-mediated diseases and response to vaccination. Brian is currentlyinvestigating canine endocrine disease, more specifically working to understand the pathogenesis of diabetes mellitus, hypothyroidism and hypoadrenocorticism in dogs.

Brianis also involved in a studycharacterising canine innate immune response genes to determine whether these are involved in susceptibility to various disease syndromes (including anal furunculosis and inflammatory bowel disease). Alongside this, Brian is also examining the genetics of vaccine responses in dogs; how immune response genes can influence the response to vaccination and how immunosenescence impacts on the immune response as dogs get older.

Addisons disease (hypoadrenocorticism) is an autoimmune condition that occurs in dogs when the immune system attacks and destroys the adrenal gland, leading to a deficiency of steroid hormones.

We are interested in the genetics and autoimmune response in canine Addisons disease and have identified autoantibodies in the blood that react to proteins in the adrenal gland. We are interested in carrying out further research into this disease, to measure these autoantibodies, to see whether they can be used as part of diagnostic testing and potentially to identify dogs that have an autoimmune reaction, before they develop clinical signs. We are keen to recruit dogs that are undergoing blood sampling as part of diagnostic testing for Addisons disease or who are being monitored for their response to steroid replacement therapy.

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1: Dutton LC, Dudhia J, Catchpole B, Hodgkiss-Geere H, Werling D, Connolly DJ.Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2acting via the EP4 receptor. Sci Rep. 2018 Sep 6;8(1):13351. doi:10.1038/s41598-018-31569-1. PubMed PMID: 30190508; PubMed Central PMCID:PMC6127326.

2: Boag AM, Christie MR, McLaughlin KA, Syme HM, Graham P, Catchpole B. Alongitudinal study of autoantibodies against cytochrome P450 side-chain cleavageenzyme in dogs (Canis lupus familiaris) affected with hypoadrenocorticism(Addison's disease). Vet Immunol Immunopathol. 2018 Aug;202:41-45. doi:10.1016/j.vetimm.2018.05.013. Epub 2018 May 26. PubMed PMID: 30078597.

3: Soutter F, Martorell S, Solano-Gallego L, Catchpole B. Inconsistent MHC classII association in Beagles experimentally infected with Leishmania infantum. VetJ. 2018 May;235:9-15. doi: 10.1016/j.tvjl.2018.03.001. Epub 2018 Mar 7. PubMedPMID: 29704945.

4: Holder A, Jones G, Soutter F, Palmer DB, Aspinall R, Catchpole B.Polymorphisms in the canine IL7R 3'UTR are associated with thymic output inLabrador retriever dogs and influence post-transcriptional regulation by microRNA185. Dev Comp Immunol. 2018 Apr;81:244-251. doi: 10.1016/j.dci.2017.12.008. Epub2017 Dec 14. PubMed PMID: 29247721.

5: Holder A, Mirczuk SM, Fowkes RC, Palmer DB, Aspinall R, Catchpole B.Perturbation of the T cell receptor repertoire occurs with increasing age indogs. Dev Comp Immunol. 2018 Feb;79:150-157. doi: 10.1016/j.dci.2017.10.020. Epub2017 Oct 28. PubMed PMID: 29103899; PubMed Central PMCID: PMC5711257.

6: Dutton LC, Church SAV, Hodgkiss-Geere H, Catchpole B, Huggins A, Dudhia J,Connolly DJ. Cryopreservation of canine cardiosphere-derived cells: Implicationsfor clinical application. Cytometry A. 2018 Jan;93(1):115-124. doi:10.1002/cyto.a.23186. Epub 2017 Aug 22. PubMed PMID: 28834400.

7: O'Kell AL, Wasserfall C, Catchpole B, Davison LJ, Hess RS, Kushner JA,Atkinson MA. Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice,and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?Diabetes. 2017 Jun;66(6):1443-1452. doi: 10.2337/db16-1551. PubMed PMID:28533295; PubMed Central PMCID: PMC5440022.

8: Davison LJ, Holder A, Catchpole B, O'Callaghan CA. The Canine POMC Gene,Obesity in Labrador Retrievers and Susceptibility to Diabetes Mellitus. J VetIntern Med. 2017 Mar;31(2):343-348. doi: 10.1111/jvim.14636. Epub 2017 Feb 8.Erratum in: J Vet Intern Med. 2017 Jul;31(4):1362. PubMed PMID: 28176381; PubMedCentral PMCID: PMC5354034.

9: Scudder CJ, Niessen SJ, Catchpole B, Fowkes RC, Church DB, Forcada Y. Felinehypersomatotropism and acromegaly tumorigenesis: a potential role for the AIPgene. Domest Anim Endocrinol. 2017 Apr;59:134-139. doi:10.1016/j.domaniend.2016.11.005. Epub 2016 Dec 8. PubMed PMID: 28119176.

10: Peiravan A, Allenspach K, Boag AM, Soutter F, Holder A, Catchpole B, KennedyLJ, Werling D, Procoli F. Single nucleotide polymorphisms in majorhistocompatibility class II haplotypes are associated with potential resistanceto inflammatory bowel disease in German shepherd dogs. Vet Immunol Immunopathol.2016 Dec;182:101-105. doi: 10.1016/j.vetimm.2016.10.012. Epub 2016 Oct 22. PubMedPMID: 27863539.

11: Holder A, Mella S, Palmer DB, Aspinall R, Catchpole B. An Age-AssociatedDecline in Thymic Output Differs in Dog Breeds According to Their Longevity. PLoSOne. 2016 Nov 8;11(11):e0165968. doi: 10.1371/journal.pone.0165968. eCollection2016. PubMed PMID: 27824893; PubMed Central PMCID: PMC5100965.

12: Boag AM, Christie MR, McLaughlin KA, Syme HM, Graham P, Catchpole B.Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canislupus familiaris) Affected with Hypoadrenocorticism (Addison's Disease). PLoSOne. 2015 Nov 30;10(11):e0143458. doi: 10.1371/journal.pone.0143458. eCollection2015. PubMed PMID: 26618927; PubMed Central PMCID: PMC4664467.

13: Threlfall AJ, Boag AM, Soutter F, Glanemann B, Syme HM, Catchpole B. Analysisof DLA-DQB1 and polymorphisms in CTLA4 in Cocker spaniels affected withimmune-mediated haemolytic anaemia. Canine Genet Epidemiol. 2015 Jun 9;2:8. doi:10.1186/s40575-015-0020-y. eCollection 2015. PubMed PMID: 26401336; PubMedCentral PMCID: PMC4579385.

14: Holder AL, Kennedy LJ, Ollier WE, Catchpole B. Breed differences indevelopment of anti-insulin antibodies in diabetic dogs and investigation of therole of dog leukocyte antigen (DLA) genes. Vet Immunol Immunopathol. 2015 Oct15;167(3-4):130-8. doi: 10.1016/j.vetimm.2015.07.014. Epub 2015 Aug 2. PubMedPMID: 26272177.

15: Boag AM, Catchpole B. A review of the genetics of hypoadrenocorticism. TopCompanion Anim Med. 2014 Dec;29(4):96-101. doi: 10.1053/j.tcam.2015.01.001. Epub2015 Jan 5. Review. PubMed PMID: 25813849.

16: Killick DR, Stell AJ, Catchpole B. Immunotherapy for canine cancer--is ittime to go back to the future? J Small Anim Pract. 2015 Apr;56(4):229-41. doi:10.1111/jsap.12336. Epub 2015 Feb 23. Review. PubMed PMID: 25704119.

17: Soutter F, Kennedy LJ, Ollier WE, Solano-Gallego L, Catchpole B. Restricteddog leucocyte antigen (DLA) class II haplotypes and genotypes in Beagles. Vet J.2015 Mar;203(3):345-7. doi: 10.1016/j.tvjl.2014.12.032. Epub 2015 Jan 5. PubMedPMID: 25634081; PubMed Central PMCID: PMC4366010.

18: Adams JP, Holder AL, Catchpole B. Recombinant canine single chain insulinanalogues: insulin receptor binding capacity and ability to stimulate glucoseuptake. Vet J. 2014 Dec;202(3):436-42. doi: 10.1016/j.tvjl.2014.09.027. Epub 2014Oct 5. PubMed PMID: 25457265.

19: Short AD, Catchpole B, Boag AM, Kennedy LJ, Massey J, Rothwell S, HenthornPS, Littman MP, Husebye E, Ollier B. Putative candidate genes for caninehypoadrenocorticism (Addison's disease) in multiple dog breeds. Vet Rec. 2014 Nov1;175(17):430. doi: 10.1136/vr.102160. Epub 2014 Aug 14. PubMed PMID: 25124887.

20: Kathrani A, Lee H, White C, Catchpole B, Murphy A, German A, Werling D,Allenspach K. Association between nucleotide oligomerisation domain two (Nod2)gene polymorphisms and canine inflammatory bowel disease. Vet ImmunolImmunopathol. 2014 Sep 15;161(1-2):32-41. doi: 10.1016/j.vetimm.2014.06.003. Epub2014 Jun 26. PubMed PMID: 25017709.

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OMIM Entry – * 104311 – PRESENILIN 1; PSEN1

Posted: March 8, 2019 at 6:43 am

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The rest is here:
OMIM Entry - * 104311 - PRESENILIN 1; PSEN1

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Learn Zone – VetCompass – Royal Veterinary College, RVC

Posted: January 27, 2019 at 9:40 am

Veterinary Epidemiology in Practice - The VetCompass Programme

Dr. Dan O'Neill (VetCompass, RVC)

In this e-lecture, recorded as part of the VET Talks series hosted by the RVC, Dr Dan O'Neill gives an overview of practice-based veterinary epidemiological research and describes the important role of VetCompass in pushing the boundaries of this exciting new field.

Dr. Dan O'Neill (VetCompass, RVC) & Dr. Katy Evans (University of Nottingham) British Small Animal Veterinary Association Annual Congress, 2015

This talk was delivered at BSAVA Congress 2015 and addresses the importance of generating high quality evidence to inform decision-making for the improvement of canine welfare. Dr. Dan ONeill and Dr. Katy Evans discuss the importance of evidence-based veterinary advice when aiming to improve dog health at a population level, highlighting how large-scale, ongoing health surveillance projects such as VetCompass are vital in providing relevant, representative findings for practical use by clinicians.

This audio recording is shared by kind permission of the UK Kennel Club.

Dr. Dan O'Neill (VetCompass, RVC) & Aimee Llewellyn (Geneticist & Health Information Manager, UK Kennel Club)British Small Animal Veterinary Association Annual Congress, 2015

This talk was delivered as part of the first ever BSAVA lecture stream on Practical aspects of dog breeding. Dr. Dan ONeill and Aimee Llewellyn (of the Royal Veterinary College & UK Kennel Club respectively) presented information on the practical approaches veterinary practices can take to improve the advice they give to breeder clients. Bothspeakers emphasised the vital role that veterinary practitioners can play in improving dog health at a population level and highlighted the importance of large-scale, ongoing health surveillance projects such as VetCompass.

This audio recording is shared by kind permission of the UK Kennel Club.

Discussinghowwe canuse the information contained in veterinary clinical records to better understand pain-related welfare in companion animals

A short video about VetCompass with examples of evidence generated, with musical accompaniment (no speaker)

Information on the expected lifespan and causes of death in dogs in England based on a VetCompass Programme study

Find out how common epilepsy is in dogs and which breeds are affected

McGreevy, PD, Wilson BJ, Mansfield, CS.Church DB, Brodbelt DC, Dhand, N,Soares Magalhaes, RJ and O'Neill DG. (2018)Canine Genetics and Epidemiology

O'Neill DG, Baral L, Church DB, Brodbelt DC and Packer RMA (2018) Canine Genetics and Epidemiology 5:3.

O'Neill DG, Darwent EC, Church DB and Brodbelt DC (2017) Canine Genetics and Epidemiology 4:15

O'Neill DG, Yin Seah W, Church DB and Brodbelt DC (2017) Canine Genetics and Epidemiology 4:13

O'Neill DG, Coulson NR, Church DB and Brodbelt DC (2017) Canine Genetics and Epidemiology 4:7

O'Neill DG, Darwent EC, Church DB andBrodbelt DC (2016) Canine Genetics and Epidemiology, 3(1):1-12.

Summers JF, ONeill DG, Church DB, Thomson PC, McGreevy PD and Brodbelt DC. (2015) Canine Genetics and Epidemiology.

Boyd, C., Jarvis, S., McGreevy, P., Heath, S., Church, D., Brodbelt, D., and O'Neill, DG. (2018)Animal Welfare

Conroy, M., O'Neill, DG., Boag, A., Church, DB., and Brodbelt, DC. (2018). Journal of Small Animal Practice.

McDonald JL, Cleasby LR, Brodblet DC, Church DB and O'Neill DG (2017) Journal of Small Animal Practice DOI: 10.1111/jsap.12716, n/a-n/a. (Early view)

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) Veterinary Journal.

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) Journal of Feline Medicine and Surgery.

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC(2014) PLoS One,9(3).

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC(2013) The Veterinary Journal,198,638-643.

Mattin MJ, Boswood A, Church DB, Brodbelt DC (2018) Journal of Veterinary Internal Medicine

Mattin MJ, Boswood A, Church DB, McGreevy PD, O'Neill DG, Thomson PC, Brodbelt DC. (2015; Epub ahead of print) Preventive Veterinary Medicine

Mattin MJ, Boswood A, Church DB, Lpez-Alvarez J, McGreevy PD, O'Neill DG, Thomson PC, Brodbelt DC. (2015) Journal of Veterinary Internal Medicine

O'Neill DG, Gostelow R, Orme C, Church D., Niessen SJM, Verheyen K & Brodbelt DC (2016) Journal of Veterinary Internal Medicine

O'Neill DG, Scudder C, Faire JM, Church DB, McGreevy PD, Thomson PC andBrodbelt DC(2016)Journal of Small Animal Practice2016

Mattin MJ, O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) The Veterinary Record,174(14), 349.

Stephens MJ, O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) The Veterinary Record.

O'Neill DG, Case J, Boag AK, Church DB, McGreevy PD, Thomson PC & Brodbelt DC (2017) Journal of Small Animal Practice, DOI: 10.1111/jsap.12723, n/a-n/a

Erlen A, Potschka H, Volk HA, Sauter-Louis C, O'Neill DG, (2018) Journal of Veterinary Internal Medicine.

Kearsley-Fleet L, O'Neill DG, Volk HA, Chursh DB, Brodbelt DC (2013) The Veterinary Record;30;172

O'Neill, DG., Corah, CH., Church, DB., Brodbelt, DC., and Rutherford, L. (2018).Canine Genetics and Epidemiology

Shoop SJ,Marlow S,Church DB,English K,McGreevy PD,Stell AJ,Thomson PC,O'Neill DGandBrodbelt DC (2014) Canine Genetics and Epidemiology.

O'Neill, D.G., Lee, M.M, Brodbelt, D.C., Church, D.B. & Sanchez, R.F. (2017) Canine Genetics and Epidemiology 4:5

Anderson KL, O'Neill DG, Brodbelt DC, Church DB, Meeson RL, Sargan D, Summers JF, Zulch H & Collins LM(2018)Scientific Reports

O'Neill DG, Meeson RL, Sheridan A, Church DB andBrodbelt DC (2016) Canine Genetics and Epidemiology

Taylor-Brown FE, Meeson RL, Brodbelt DC, Church DB, McGreevy PD, Thomson PC & O'Neill DG. (2015) Veterinary Surgery

O'Neill D, Jackson C, Guy J, Church D, McGreevy P, Thomson P. & Brodbelt D.(2015) Canine Genetics and Epidemiology

Stevens K.B., O'Neill D.G., Jepson R., Holm L.P., Walker D.J., andCardwell J.M.(2018) Veterinary Record

Hall, J.L., Owen, L., Riddell, A., Church, D.B., Brodbelt, D.C., and O'Neill D.G., (2018)Journal of Small Animal Practice.

O'Neill D.G., O'Sullivan AM, Manson EA, Church DB, Boag AK, McGreevy PD and Brodbelt D.C. and (2017)VeterinaryRecordDOI:10.1136/vr.104108 DOI:10.1111/jsap.12731

O'Neill D.G., Riddell A., Church D.B., Owen L., Brodbelt D.C. and Hall J.L. (2017) Journal of Small Animal Practice DOI:10.1111/jsap.12731

O'Neill DG, Elliott J, Church DB, McGreevy PD, Thomson PC, Brodbelt DC(2013) Journal of Veterinary Internal Medicine;27(4):814-21

Buckland, E., O'Neill, D., Summers, J., Mateus, A., Church, D., Redmond, L. and Brodbelt, D. Veterinary Record (2016) doi:10.1136/vr.103830

Summers JF, Hendricks A, Brodbelt DC (2014) BMC Veterinary Research.

O'Neill DG, Hendricks A, Summers JF,Brodbelt DC(2012) J Small Anim Pract;53(4): 217-22

Muellner, P., Muellner, U., Gates, M. C., Pearce, T., Ahlstrom, C., O'Neill, D., Brodblet, D. & Cave, N. J. (2016) Frontiers in Veterinary Science, 3.

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC (2014) Canine Genetics and Epidemiology,1:2.

Hoffman, J.M., Creevy, K.E., Franks, A., O'Neill, D.G. and Promislow, D.E.L. (2018) Aging Cell.

Hoffman, J.M., O'Neill, D.G., Creevy, K.E., & Austad, S.N.(2018)The Journals of Gerontology: Series A, 73, 150-156.

Jin, K., Hoffman, J.M., Creevy, K.E., O'Neill, D.G. and Promislow, D.E.L. (2016) Pathobiology of Aging and Age-related Diseases6:33276

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Learn Zone - VetCompass - Royal Veterinary College, RVC

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Dr Emille Reid | Physician | Kuils River | Cape Town

Posted: July 17, 2016 at 6:40 am

Practice Details Practice Number: 0175986 Qualifications: MBChB (Stell), MMed(Int)(Stell), DipHIVMan(CMSA), BScHons(MedSc)(Epidemiology&Statistics)(Stell) Office Contact Person: Hanli, Amelia or Fatima (Practice manager) Telephone No: 021948 4776 Fax No: 021948 3350 Cell No: 083292 4212 After Hours Telephone No: 083292 4212 Email Address: emille@egreid.com Website Address: Physical Address: Suite 4H, Fourth Floor, Riverside View, Netcare Kuils River, Van Riebeeck Road, Kuils River, 7580 Social Networks Postal Address: PO Box 150, Soneike, 7583 Detailed information and specialities Emille Reid is a specialist with an interest in Infectious Diseases. He runs a busy HIV clinic (as part of his general practice) and provide evidence-based in-hospital care as part of a supportive medical team of specialists at the Netcare Kuils River Hospital. He has a particular interest in caring for the critically ill whilst in icu as well as those suffering from HIV, TB and general- and tropical infections infections. He is a keen teacher who very often give lectures at medical school and provide training to nurses, general practitioners and specialists. Contact Form Please feel free to contact the doctor or if you have any questions for the doctor please fill in the form below: Map GPS Co-Ordinates: View Larger Map

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Dr Emille Reid | Physician | Kuils River | Cape Town

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Edward A. Stadtmauer, MD profile | PennMedicine.org

Posted: at 6:40 am

International Myeloma Working Group, Member

American College of Physicians, Fellow

American Federation for Clinical Research, 1993-94 Eastern Section, Hematology/Oncology Session Chairman

American Society for Blood and Marrow Transplantation

American Society of Clinical Oncology, 1995-96 Member, ASCO Program Committee 1995-96 Member, Bone Marrow Transplantation, High Dose Chemotherapy and Cytokines Subcommittee 2004-present Member, Editorial Board Journal of Clinical Oncology

American Society of Hematology, 2001,2004,2008, 2010 Abstract Reviewer/Session Moderator, Clinical Bone Marrow Transplantation

Autologous Bone Marrow Transplant Registry (ABMTR/CIBMTR), 2000-2006 Member, ABMTR Advisory Board 2004-2006 Member, ABMTR Executive Committee 2004-2006 Chairman, ABMTR Nominating Committee 2006-2008 Member, CIBMTR Nominating Committee 2006-2008 Member, CIBMTR Advisory Committee 2008-Present Co-Chair, CIBMTR Solid Tumor Working Committee 2006-present Member, CIBMTR Clinical Trials Advisory Committee

Bone Marrow Transplant Clinical Trials Network, 2001-Principal Investigator, University of Pennsylvania 2001-2005 Chairman, Administration/Operations Committee 2001-2005 Member, Executive Committee 2001-Present Member, Steering Committee 2001-Present Member, Member, Publications Committee, Chair 2007-2011 2005-Present Member, BMT-CTN Myeloma Intergroup Working Committee, Chair 2012-Present 2006-Present, Chair, Publications Committee

Eastern Cooperative Oncology Group, 1990-Member, Bone Marrow Transplant Core Committee 1993-Co-chairman, Bone Marrow Transplant Committee 1991-Member, Leukemia Core Committee 1992-Member, Myeloma Core Committee 1998-Member, Lymphoma Core Committee

Foundation for the Accreditation of Hematopoietic Cell Therapy, 1999-Inspection Team, Member 1999-Team Leader, Clinical Program Inspector 2000-Stem Cell Collection Facility Inspector 2004-Member, Accrediation Committee

Membership in National Scientific Review Panels, 2002, Ad hoc Member, NIH Clinical Oncology Study Section 2005-present, Ad hoc Member, NHLBI Program Project Reviews 2006-present, Member, Leukemia and Lyumphoma Society, Clinical Development Program, Grant Review Subcommittee

NIAID Hematopoietic Stem Cell Transplantation Data Safety Monitoring Board (HSCT DSMB), 2005-present, Member

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Edward A. Stadtmauer, MD profile | PennMedicine.org

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Publish and perish? – Sveriges Unga Akademi

Posted: at 6:40 am

Bruce Alberts Former Editor in Chief at Science, former President of the National Academy of Sciences, USA

Tony Hyman Research Group Leader and Director, The Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Arne Johansson Professor in Mechanics, Vice President,the Royal Institute of Technology (KTH)

Catriona MacCallum Senior Advocacy Manager PLOS, and Consulting Editor at PLOS ONE

Tommy Ohlsson Professor in Theoretical Physics at the Royal Institute of Technology (KTH)

Brandon Stell Research Associate, CNRS, Co-Team Leader, Laboratoire de Physiologie Crbrale Universit Paris Descartes

09.30 Coffee

10.00 Welcome!

10.10 How can a nation support excellence in scientific research and teaching? Bruce Alberts

11.00 Publication assessment and university governance Arne Johansson

11.30 Encouraging innovation through peer review and evaluation Tony Hyman

12.00 Lunch

12.45 Scientific Communication on Trial Catriona MacCallum

13.15 Open Access Publishing with arXiv Tommy Ohlsson

13.45 Coffee

14.15 Introducing PubPeer Brandon Stell

14.45 Panel discussion 15.30 End

This year marks the 350th anniversary of the longest running scientific journal: The Philosophical Transactions of the Royal Society (London). Already at its inception, it had the fundamental functions usually associated with scientific publishing such as registration of submission and publication dates, peer review, and means for dissemination and archiving. Today scientific publishing is more important than ever, with the number of journals rapidly growing, and the perceived success of a scientist to an increasing degree defined by scientific publications, with particular pressure to publish in so-called high-impact journals. In parallel these trends appear to put in question the value of the traditional scientific peer review, both in the publication process where newsworthiness, impact and potential for citations may trump scientific rigor, and in evaluation for tenured positions, where bibliometric indices and impact assessment tools risk reducing a young scientists work to a number.

At the seminar we will discuss the rapidly changing scientific publishing landscape and its implications. How does the increasing number of journals and the increasing focus on journal impact change how science is carried out and how young scientist choose their topics and plan their research? What is the impact of entirely open and non-reviewed pre-publication online archives are they promising new solutions to effective dissemination and open science, or of little value to young scientists when evaluations put a premium on journal impact? Is the pre-publication peer review model faltering under the increasing volume of peer review and the shrinking time and effort available for peer review? Can post-publication peer review offer a more sustainable solution? Are universities over-relying on bibliometric tools when assessing the value of their tenured researchers and when hiring new researchers?

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Publish and perish? - Sveriges Unga Akademi

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Stem Cell Biology – mmrl.edu

Posted: at 6:40 am

The recent technology termed Cellular Reprogramming enables creation of a versatile type of stem cells called induced Pluripotent Stem Cells (iPSC) from any somatic tissue, such as skin, blood, adipose tissue from liposuction and hair follicles from plucked hair. These stem cells have 2 important characteristics: 1) the potential to proliferate indefinitely in culture and 2) the potential to give rise to any cell type including heart, brain, liver and insulin secreting beta cells, when provided with appropriate environment and stimuli. These cells hold promise for cell-based regenerative therapy of degenerative diseases, including heart failure, Parkinsons disease, Alzheimers disease, blindness and diabetes mellitus.

These induced pluripotent stem cells also permit the development of human models of disease using cells isolated from patients with various diseases. These cells, for example, can be directed to differentiate into heart cells, thus providing cells that have the genetic defect that the patients heart has, paving the way for the development of personalized treatments.

Sudden cardiac death claims the lives of approximately 350,000 Americans each year. Nearly 50% of all coronary deaths are sudden, occurring within 1 hour of the onset of symptoms. Sudden death after a heart attack is commonly due to a cardiac arrhythmia known as ventricular fibrillation and evidence is emerging that a genetic predisposition contributes to the development of life-threatening arrhythmias. In the absence of coronary disease, sudden cardiac death is often due to inherited cardiac arrhythmia syndromes such as long QT, short QT, Brugada and Early Repolarization syndromes that involve genetic defects. To better understand the molecular and cellular mechanisms underlying these arrhythmic syndromes and to develop effective therapeutic measures, reliable experimental models of the disease are needed and are being developed using these induced pluripotent stem cells.

The principal research focus at the MMRL Stem Cell Center is therefore 1) to elucidate the pathophysiological mechanisms underlying life threatening arrhythmic cardiac diseases using patient-specific iPSC-based human in vitro models and 2) to generate heart cells from skin cells-derived iPSCs using genetic engineering and pharmacological approaches for cell-based regenerative therapy of heart failure.

Fig 1

A 3mm by 3 mm skin punch biopsy excised by the physician as shown in Figure 1 provides enough material to generate these stem cells. Immediately after excision, the skin biopsy is processed to isolate fibroblasts. The fibroblasts are then reprogrammed using transcriptional factors (Oct4, Sox2, Klf4 and c-Myc) to generate induced Pluripotent Stem Cells over a period of 4-5 weeks in culture, as shown in Figure 2. These stem cells have the same genetic makeup including the genetic information responsible for the disease, as that of the patient whose skin biopsy was obtained. These stem cells are later directed to become beating heart cells using distinct molecules and micro-environmental factors. These beating miniaturized heart tissues in the petri dish have the ability to mirror the patients heart problem and can therefore serve as experimental models of the human disease to be used to determine the underlying disease mechanism and to formulate effective therapeutic measures. Figure 3 shows rhythmically contracting iPSC-derived heart tissue from a healthy individual and the recording of the electrical signals and contraction.

Fig 2 ( Left ) and Fig 3 ( Right )

Over 5 million Americans suffer from congestive heart failure. Heart failure is characterized by the loss of functional heart cells and thereby its inability to pump enough blood to maintain physiological functions. The last resort for the patients with end stage heart failure is heart transplantation. Often, this is limited by the availability of a perfectly matched organ. The demand for organ supply is increasing steadily, necessitating development of new therapeutic options. iPSCs-derived heart tissues hold great potential for cellular transplantation in failing hearts in that these cells could be derived from the skin biopsy of the patient needing transplantation and will be transplanted back to the same individual thereby hopefully obviating the need for immune rejection therapy. The replacement of scar tissue by stem cell-derived heart cells could improve heart function obviating the need for heart transplantation. Scientists in our Stem Cell Center are working to generate billions of clinical grade heart cells from skin cells-derived iPSC using genetic engineering and pharmacological approaches for cell-based regenerative therapy of heart failure.

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Stem Cell Biology - mmrl.edu

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BRAIN PLASTICITY AND BEHAVIOR – Annual Review of …

Posted: at 6:40 am

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BRAIN PLASTICITY AND BEHAVIOR - Annual Review of ...

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