http://www.dspace.cam.ac.uk:80/handle/1810/221811 Tue, 21 May 2013 21:34:51 GMT 2013-05-21T21:34:51Z http://www.dspace.cam.ac.uk:80/handle/1810/244396 Title: Transcriptional functions of the corepressor Sin3A in skin Authors: Cox, Claire Abstract: Upon activation in epidermal stem cells, the proto-oncogene c-Myc triggers their exit from the stem cell compartment resulting in an increase in progenitor cell proliferation and an induction in terminal differentiation. Whether c-Myc plays a direct transcriptional role in epidermal stem cell differentiation was unknown. The exploration of c-Myc's transcriptional roles at the epidermal differentiation complex (EDC), a locus essential for skin maturation demonstrated that binding of c-Myc to the EDC can simultaneously recruit and displace specific sets of differentiation-specific transcriptional regulators to EDC genes. Among these factors, Sin3A acts as a transcriptional co-repressor and was initially discovered via its direct interaction with Mxi1 and Mxd1, which are antagonists of the Myc family network. As such, I concentrated on the role of Sin3A as a potential opposing factor to c-Myc activity in the epidermis. To analyse the role of Sin3A in regulating epidermal stem cell fate in vivo, I generated a number of transgenic mouse models. To determine whether Sin3A functions in hair follicle stem cells, I inducibly deleted Sin3A in the hair follicle bulge, where quiescent stem cells reside. However, lack of Sin3A in the hair bulge did not cause any aberrant phenotype and I concluded that Sin3A is dispensable for hair follicle homeostasis. I next analysed a mouse model in which Sin3A is inducibly deleted in the basal layer of the epidermis. Deletion of Sin3A resulted in a severe disruption of epidermal homeostasis-namely due to increases in proliferation and differentiation. Further investigation demonstrated that this phenotype is driven by enhanced genomic recruitment of c-Myc to the epidermal differentiation complex and reactivation of c-Myc target genes involved in cellular proliferation. I found that Sin3A causes de-acetylation of the c-Myc protein to directly repress c-Myc’s transcriptional activity and is antagonistic to c-Myc in the interfollicular epidermis. I hypothesised that simultaneous deletion of Sin3A and c-Myc might return the skin to normality. Indeed, when Sin3A and Myc are concurrently deleted, proliferation and differentiation levels returned to normal. These results demonstrate how levels of Sin3A and c-Myc must be carefully balanced for epidermal homeostasis to be maintained. Decreased expression of Sin3A has been linked to tumour susceptibility in other tissues for example in non-small cell lung carcinoma making Sin3A a candidate tumour suppressor gene. I therefore considered that loss of Sin3A may lead to increased susceptibility to skin cancer. To investigate this I performed pilot experiments using UVB irradiation of skin that has one copy of Sin3A deleted in the basal layer of the epidermis. Under normal conditions, these mice have no identifiable phenotype, but pilot experiments demonstrated that after short term and long term UVB irradiation, they exhibit increased epidermal thickness and proliferation relative to controls. This recapitulated the phenotype observed when Sin3A is inducibly deleted in the interfollicular epidermis and further demonstrates the role of SinA as an inhibitor of proliferation in this tissue. Overall, these results demonstrate that an interplay between the opposing functions of Sin3A and c-Myc are necessary to ensure that there is balanced homeostasis in the interfollicular epidermis. Tue, 12 Mar 2013 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244396 2013-03-12T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241586 Title: Hyperalgesic activity of kisspeptin in mice Authors: Spampinato, Simona; Trabucco, Angela; Biasiotta, Antonella; Biagioni, Francesca; Cruccu, Giorgio; Copani, Agata; Colledge, William H; Sortino, Maria Angela; Nicoletti, Ferdinando; Chiechio, Santina Abstract: Abstract Background Kisspeptin is a neuropeptide known for its role in the hypothalamic regulation of the reproductive axis. Following the recent description of kisspeptin and its 7-TM receptor, GPR54, in the dorsal root ganglia and dorsal horns of the spinal cord, we examined the role of kisspeptin in the regulation of pain sensitivity in mice. Results Immunofluorescent staining in the mouse skin showed the presence of GPR54 receptors in PGP9.5-positive sensory fibers. Intraplantar injection of kisspeptin (1 or 3 nmol/5 μl) induced a small nocifensive response in naive mice, and lowered thermal pain threshold in the hot plate test. Both intraplantar and intrathecal (0.5 or 1 nmol/3 μl) injection of kisspeptin caused hyperalgesia in the first and second phases of the formalin test, whereas the GPR54 antagonist, p234 (0.1 or 1 nmol), caused a robust analgesia. Intraplantar injection of kisspeptin combined with formalin enhanced TRPV1 phosphorylation at Ser800 at the injection site, and increased ERK1/2 phosphorylation in the ipsilateral dorsal horn as compared to naive mice and mice treated with formalin alone. Conclusion These data demonstrate for the first time that kisspeptin regulates pain sensitivity in rodents and suggest that peripheral GPR54 receptors could be targeted by novel drugs in the treatment of inflammatory pain. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 23 Nov 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241586 2011-11-23T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/240641 Title: Improving ontologies by automatic reasoning and evaluation of logical definitions Authors: Kohler, Sebastian; Bauer, Sebastian; Mungall, Chris J; Carletti, Gabriele; Smith, Cynthia L; Schofield, Paul; Gkoutos, George V; Robinson, Peter N Abstract: Abstract Background Ontologies are widely used to represent knowledge in biomedicine. Systematic approaches for detecting errors and disagreements are needed for large ontologies with hundreds or thousands of terms and semantic relationships. A recent approach of defining terms using logical definitions is now increasingly being adopted as a method for quality control as well as for facilitating interoperability and data integration. Results We show how automated reasoning over logical definitions of ontology terms can be used to improve ontology structure. We provide the Java software package GULO (Getting an Understanding of LOgical definitions), which allows fast and easy evaluation for any kind of logically decomposed ontology by generating a composite OWL ontology from appropriate subsets of the referenced ontologies and comparing the inferred relationships with the relationships asserted in the target ontology. As a case study we show how to use GULO to evaluate the logical definitions that have been developed for the Mammalian Phenotype Ontology (MPO). Conclusions Logical definitions of terms from biomedical ontologies represent an important resource for error and disagreement detection. GULO gives ontology curators a fast and simple tool for validation of their work. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 26 Oct 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/240641 2011-10-26T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/240577 Title: Auditory-based processing of communication sounds Authors: Walters, Thomas C. Abstract: This thesis examines the possible benefits of adapting a biologically-inspired model of human auditory processing as part of a machine-hearing system. Features were generated by an auditory model, and used as input to machine learning systems to determine the content of the sound. Features were generated using the auditory image model (AIM) and were used for speech recognition and audio search. AIM comprises processing to simulate the human cochlea, and a ‘strobed temporal integration’ process which generates a stabilised auditory image (SAI) from the input sound. The communication sounds which are produced by humans, other animals, and many musical instruments take the form of a pulse-resonance signal: pulses excite resonances in the body, and the resonance following each pulse contains information both about the type of object producing the sound and its size. In the case of humans, vocal tract length (VTL) determines the size properties of the resonance. In the speech recognition experiments, an auditory filterbank was combined with a Gaussian fitting procedure to produce features which are invariant to changes in speaker VTL. These features were compared against standard mel-frequency cepstral coefficients (MFCCs) in a size-invariant syllable recognition task. The VTL-invariant representation was found to produce better results than MFCCs when the system was trained on syllables from simulated talkers of one range of VTLs and tested on those from simulated talkers with a different range of VTLs. The image stabilisation process of strobed temporal integration was analysed. Based on the properties of the auditory filterbank being used, theoretical constraints were placed on the properties of the dynamic thresholding function used to perform strobe detection. These constraints were used to specify a simple, yet robust, strobe detection algorithm. The syllable recognition system described above was then extended to produce features from profiles of the SAI and tested with the same syllable database as before. For clean speech, performance of the features was comparable to that of those generated from the filterbank output. However when pink noise was added to the stimuli, performance dropped more slowly as a function of signal-to-noise ratio when using the SAI-based AIM features, than when using either the filterbank-based features or the MFCCs, demonstrating the noise-robustness properties of the SAI representation. The properties of the auditory filterbank in AIM were also analysed. Three models of the cochlea were considered: the static gammatone filterbank, dynamic compressive gammachirp (dcGC) and the pole-zero filter cascade (PZFC). The dcGC and gammatone are standard filterbank models, whereas the PZFC is a filter cascade, which more accurately models signal propagation in the cochlea. However, while the architecture of the filterbanks is different, they have all been successfully fitted to psychophysical masking data from humans. The abilities of the filterbanks to measure pitch strength were assessed, using stimuli which evoke a weak pitch percept in humans, in order to ascertain whether there is any benefit in the use of the more computationally efficient PZFC. Finally, a complete sound effects search system using auditory features was constructed in collaboration with Google research. Features were computed from the SAI by sampling the SAI space with boxes of different scales. Vector quantization (VQ) was used to convert this multi-scale representation to a sparse code. The ‘passive-aggressive model for image retrieval’ (PAMIR) was used to learn the relationships between dictionary words and these auditory codewords. These auditory sparse codes were compared against sparse codes generated from MFCCs, and the best performance was found when using the auditory features. Mon, 06 Jun 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/240577 2011-06-06T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/240573 Title: Regulation of chemotropic guidance of nerve growth cones by microRNA Authors: Han, Liang; Wen, Zhexing; Lynn, Rachel C; Baudet, Marie-Laure; Holt, Christine E; Sasaki, Yukio; Bassell, Gary J; Zheng, James Q Abstract: Abstract Background The small non-coding microRNAs play an important role in development by regulating protein translation, but their involvement in axon guidance is unknown. Here, we investigated the role of microRNA-134 (miR-134) in chemotropic guidance of nerve growth cones. Results We found that miR-134 is highly expressed in the neural tube of Xenopus embryos. Fluorescent in situ hybridization also showed that miR-134 is enriched in the growth cones of Xenopus spinal neurons in culture. Importantly, overexpression of miR-134 mimics or antisense inhibitors blocked protein synthesis (PS)-dependent attractive responses of Xenopus growth cones to a gradient of brain-derived neurotrophic factor (BDNF). However, miR-134 mimics or inhibitors had no effect on PS-independent bidirectional responses of Xenopus growth cones to bone morphogenic protein 7 (BMP7). Our data further showed that Xenopus LIM kinase 1 (Xlimk1) mRNA is a potential target of miR-134 regulation. Conclusions These findings demonstrate a role for miR-134 in translation-dependent guidance of nerve growth cones. Different guidance cues may act through distinct signaling pathways to elicit PS-dependent and -independent mechanisms to steer growth cones in response to a wide array of spatiotemporal cues during development. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.; RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 03 Nov 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/240573 2011-11-03T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238663 Title: Anatomy ontologies and potential users: bridging the gap Abstract: Abstract Motivation To evaluate how well current anatomical ontologies fit the way real-world users apply anatomy terms in their data annotations. Methods Annotations from three diverse multi-species public-domain datasets provided a set of use cases for matching anatomical terms in two major anatomical ontologies (the Foundational Model of Anatomy and Uberon), using two lexical-matching applications (Zooma and Ontology Mapper). Results Approximately 1500 terms were identified; Uberon/Zooma mappings provided 286 matches, compared to the control and Ontology Mapper returned 319 matches. For the Foundational Model of Anatomy, Zooma returned 312 matches, and Ontology Mapper returned 397. Conclusions Our results indicate that for our datasets the anatomical entities or concepts are embedded in user-generated complex terms, and while lexical mapping works, anatomy ontologies do not provide the majority of terms users supply when annotating data. Provision of searchable cross-products for compositional terms is a key requirement for using ontologies. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Mon, 08 Aug 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238663 2011-08-08T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238512 Title: Does Calcium diffusional global feedback leads to slow light adaptation in Drosophila photoreceptors? - A 3D biophysical modelling approach Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Sun, 17 Jul 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238512 2011-07-17T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238264 Title: Spreading silence with Sid Authors: van Roessel, Peter; Brand, Andrea H Abstract: Abstract RNA interference (RNAi) has been shown to spread from cell to cell in plants and in Caenorhabditis elegans, but it does not spread in other organisms, such as Drosophila. A recent report demonstrates that a membrane channel, encoded by the gene sid-1, is responsible for the spreading of RNAi between cells. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Fri, 30 Jan 2004 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238264 2004-01-30T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238190 Title: High resolution transcriptome maps for wild-type and NMD mutant C. elegans through development Authors: Ramani, Arun K; Nelson, Andrew C; Kapranov, Philipp; Bell, Ian; Gingeras, Thomas R; Fraser, Andrew G Abstract: Abstract Background While many genome sequences are complete, transcriptomes are less well characterized. We used both genome-scale tiling arrays and massively parallel sequencing to map the Caenorhabditis elegans transcriptome across development. We utilized this framework to identify transcriptome changes in animals lacking the nonsense-mediated decay (NMD) pathway. Results We find that while the majority of detectable transcripts map to known gene structures, >5% of transcribed regions fall outside current gene annotations. We show that >40% of these are novel exons. Using both technologies to assess isoform complexity, we estimate that >17% of genes change isoform across development. Next we examined how the transcriptome is perturbed in animals lacking NMD. NMD prevents expression of truncated proteins by degrading transcripts containing premature termination codons. We find that approximately 20% of genes produce transcripts that appear to be NMD targets. While most of these arise from splicing errors, NMD targets are enriched for transcripts containing open reading frames upstream of the predicted translational start (uORFs). We identify a relationship between the Kozak consensus surrounding the true start codon and the degree to which uORF-containing transcripts are targeted by NMD and speculate that translational efficiency may be coupled to transcript turnover via the NMD pathway for some transcripts. Conclusions We generated a high-resolution transcriptome map for C. elegans and used it to identify endogenous targets of NMD. We find that these transcripts arise principally through splicing errors, strengthening the prevailing view that splicing and NMD are highly interlinked processes. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 23 Sep 2009 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238190 2009-09-23T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238180 Title: XGAP: a uniform and extensible data model and software platform for genotype and phenotype experiments Authors: Swertz, Morris A; van der Velde, K Joeri; Tesson, Bruno M; Scheltema, Richard A; Arends, Danny; Vera, Gonzalo; Alberts, Rudi; Dijkstra, Martijn; Schofield, Paul; Schughart, Klaus; Hancock, John M; Smedley, Damian; Wolstencroft, Katy; Goble, Carole A; de Brock, Engbert O; Jones, Andrew R; Parkinson, Helen; (CASIMIR), Coordination of Mouse Informatics Resources Consortium; (GEN2PHEN), Genotype-To-Phenotype Project; Jansen, Ritsert C Abstract: Abstract We present an extensible software model for the genotype and phenotype community, XGAP. Readers can download a standard XGAP (http://www.xgap.org) or auto-generate a custom version using MOLGENIS with programming interfaces to R-software and web-services or user interfaces for biologists. XGAP has simple load formats for any type of genotype, epigenotype, transcript, protein, metabolite or other phenotype data. Current functionality includes tools ranging from eQTL analysis in mouse to genome-wide association studies in humans. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 09 Mar 2010 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238180 2010-03-09T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238134 Title: An innovative approach to developing the reflective skills of medical students Authors: Henderson, Penny; Johnson, Martin H Abstract: Abstract Background Development of the reflective skills of medical students is an acknowledged objective of medical education. Description Description of an educational exercise which uses an email-based process for developing the reflective skills of undergraduate medical students. Student quotations illustrate learning outcomes qualitatively. Discussion The process described is immediate, direct, linked to learning objectives, enables rapid responses to be given to the students individually, and is followed by group sharing of learning. It provides a rigorous and robust feedback loop for students. It is relatively economic for teachers and incidentally benefits curriculum design and evolution. The approach supports development of a reflective approach to learning. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 09 May 2002 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238134 2002-05-09T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238104 Title: Developing essential professional skills: a framework for teaching and learning about feedback Authors: Henderson, Penny; Ferguson-Smith, Anne C; Johnson, Martin H Abstract: Abstract Background The ability to give and receive feedback effectively is a key skill for doctors, aids learning between all levels of the medical hierarchy, and provides a basis for reflective practice and life-long learning. How best to teach this skill? Discussion We suggest that a single "teaching the skill of feedback" session provides superficial and ineffective learning in a medical culture that often uses feedback skills poorly or discourages feedback. Our experience suggests that both the skill and the underlying attitude informing its application must be addressed, and is best done so longitudinally and reiteratively using different forms of feedback delivery. These feedback learning opportunities include written and oral, peer to peer and cross-hierarchy, public and private, thereby addressing different cognitive processes and attitudinal difficulties. Summary We conclude by asking whether it is possible to build a consensus approach to a framework for teaching and learning feedback skills? Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 31 Mar 2005 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238104 2005-03-31T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238080 Title: Functional studies of signaling pathways in peri-implantation development of the mouse embryo by RNAi Authors: Soares, Miguel L; Haraguchi, Seiki; Torres-Padilla, Maria-Elena; Kalmar, Tibor; Carpenter, Lee; Bell, Graham; Morrison, Alastair; Ring, Christopher J A; Clarke, Neil J; Glover, David M; Zernicka-Goetz, Magdalena Abstract: Abstract Background Studies of gene function in the mouse have relied mainly on gene targeting via homologous recombination. However, this approach is difficult to apply in specific windows of time, and to simultaneously knock-down multiple genes. Here we report an efficient method for dsRNA-mediated gene silencing in late cleavage-stage mouse embryos that permits examination of phenotypes at post-implantation stages. Results We show that introduction of Bmp4 dsRNA into intact blastocysts by electroporation recapitulates the genetic Bmp4 null phenotype at gastrulation. It also reveals a novel role for Bmp4 in the regulation the anterior visceral endoderm specific gene expression and its positioning. We also show that RNAi can be used to simultaneously target several genes. When applied to the three murine isoforms of Dishevelled, it leads to earlier defects than previously observed in double knock-outs. These include severe delays in post-implantation development and defects in the anterior midline and neural folds at headfold stages. Conclusion Our results indicate that the BMP4 signalling pathway contributes to the development of the anterior visceral endoderm, and reveal an early functional redundancy between the products of the murine Dishevelled genes. The proposed approach constitutes a powerful tool to screen the functions of genes that govern the development of the mouse embryo. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 28 Dec 2005 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238080 2005-12-28T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238068 Title: Wildlife reintroduction: considerations of habitat quality at the release site Authors: Cheyne, Susan M Abstract: Abstract Background Assessing the suitability of a habitat prior to the release of animals is vital. Proper assessment of the flora will allow reintroduction programmes to determine whether the area will be capable of supporting the released animals in the long-term. Here data are presented from an island in Central Kalimantan, Indonesia which has been used as a release site for agile gibbons (Hylobates agilis albibarbis) since January 2003. Results Methods and results regarding fruit abundance, fruit productivity, tree density and diversity are presented. This information is then analysed in the context of the island's suitability to sustain released gibbons and without impact on the resident fauna. Based on the above ecological characteristics, the final carrying capacity of the island is estimated to be between 3 and 19 gibbons. Conclusion These data highlight the need to survey areas being considered for release of gibbon prior to the release taking place. For reintroductions to be successful, long-term habitat assessment is vital, both pre- and post-release. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 12 Apr 2006 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238068 2006-04-12T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238060 Title: Welcome to Neural Development Authors: Lumsden, Andrew; Harris, Bill; Sanes, Joshua R; Wong, Rachel Abstract: Abstract[There is no abstract for this article] Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 12 Oct 2006 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238060 2006-10-12T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238059 Title: Polarization and orientation of retinal ganglion cells in vivo Authors: Zolessi, Flavio R; Poggi, Lucia; Wilkinson, Christopher J; Chien, Chi-Bin; Harris, William A Abstract: Abstract In the absence of external cues, neurons in vitro polarize by using intrinsic mechanisms. For example, cultured hippocampal neurons extend arbitrarily oriented neurites and then one of these, usually the one nearest the centrosome, begins to grow more quickly than the others. This neurite becomes the axon as it accumulates molecular components of the apical junctional complex. All the other neurites become dendrites. It is unclear, however, whether neurons in vivo, which differentiate within a polarized epithelium, break symmetry by using similar intrinsic mechanisms. To investigate this, we use four-dimensional microscopy of developing retinal ganglion cells (RGCs) in live zebrafish embryos. We find that the situation is indeed very different in vivo, where axons emerge directly from uniformly polarized cells in the absence of other neurites. In vivo, moreover, components of the apical complex do not localize to the emerging axon, nor does the centrosome predict the site of axon emergence. Mosaic analysis in four dimensions, using mutants in which neuroepithelial polarity is disrupted, indicates that extrinsic factors such as access to the basal lamina are critical for normal axon emergence from RGCs in vivo. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 12 Oct 2006 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238059 2006-10-12T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238058 Title: The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophilaneurons Authors: Pym, Edward C G; Southall, Tony D; Mee, Christopher J; Brand, Andrea H; Baines, Richard A Abstract: Abstract Background While developmental processes such as axon pathfinding and synapse formation have been characterized in detail, comparatively less is known of the intrinsic developmental mechanisms that regulate transcription of ion channel genes in embryonic neurons. Early decisions, including motoneuron axon targeting, are orchestrated by a cohort of transcription factors that act together in a combinatorial manner. These transcription factors include Even-skipped (Eve), islet and Lim3. The perdurance of these factors in late embryonic neurons is, however, indicative that they might also regulate additional aspects of neuron development, including the acquisition of electrical properties. Results To test the hypothesis that a combinatorial code transcription factor is also able to influence the acquisition of electrical properties in embryonic neurons we utilized the molecular genetics of Drosophila to manipulate the expression of Eve in identified motoneurons. We show that increasing expression of this transcription factor, in two Eve-positive motoneurons (aCC and RP2), is indeed sufficient to affect the electrical properties of these neurons in early first instar larvae. Specifically, we observed a decrease in both the fast K+ conductance (IKfast) and amplitude of quantal cholinergic synaptic input. We used charybdotoxin to pharmacologically separate the individual components of IKfast to show that increased Eve specifically down regulates the Slowpoke (a BK Ca2+-gated potassium channel), but not Shal, component of this current. Identification of target genes for Eve, using DNA adenine methyltransferase identification, revealed strong binding sites in slowpoke and nAcRα-96Aa (a nicotinic acetylcholine receptor subunit). Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRα-96Aa. Conclusion Taken together, our findings demonstrate, for the first time, that Eve is sufficient to regulate both voltage- and ligand-gated currents in motoneurons, extending its known repertoire of action beyond its already characterized role in axon guidance. Our data are also consistent with a common developmental program that utilizes a defined set of transcription factors to determine both morphological and functional neuronal properties. Thu, 16 Nov 2006 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238058 2006-11-16T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238014 Title: The evolution of imprinting: chromosomal mapping of orthologues of mammalian imprinted domains in monotreme and marsupial mammals Authors: Edwards, Carol A; Rens, Willem; Clark, Oliver; Mungall, Andrew J; Hore, Timothy; Marshall Graves, Jennifer A; Dunham, Ian; Ferguson-Smith, Anne C; Ferguson-Smith, Malcolm A Abstract: Abstract Background The evolution of genomic imprinting, the parental-origin specific expression of genes, is the subject of much debate. There are several theories to account for how the mechanism evolved including the hypothesis that it was driven by the evolution of X-inactivation, or that it arose from an ancestrally imprinted chromosome. Results Here we demonstrate that mammalian orthologues of imprinted genes are dispersed amongst autosomes in both monotreme and marsupial karyotypes. Conclusion These data, along with the similar distribution seen in birds, suggest that imprinted genes were not located on an ancestrally imprinted chromosome or associated with a sex chromosome. Our results suggest imprinting evolution was a stepwise, adaptive process, with each gene/cluster independently becoming imprinted as the need arose. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 05 Sep 2007 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238014 2007-09-05T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238003 Title: Boundary cap cells constrain spinal motor neuron somal migration at motor exit points by a semaphorin - plexin mechanism Authors: Bron, Romke; Vermeren, Matthieu; Kokot, Natalie; Little, Graham E; Mitchell, Kevin J; Andrews, William; Cohen, James Abstract: Abstract Background In developing neurons, somal migration and initiation of axon outgrowth often occur simultaneously and are regulated in part by similar classes of molecules. When neurons reach their final destinations, however, somal translocation and axon extension are uncoupled. Insights into the mechanisms underlying this process of disengagement came from our study of the behaviour of embryonic spinal motor neurons following ablation of boundary cap cells. These are neural crest derivatives that transiently reside at motor exit points, central nervous system (CNS):peripheral nervous system (PNS) interfaces where motor axons leave the CNS. In the absence of boundary cap cells, motor neuron cell bodies migrate along their axons into the periphery, suggesting that repellent signals from boundary cap cells regulate the selective gating of somal migration and axon outgrowth at the motor exit point. Here we used RNA interference in the chick embryo together with analysis of null mutant mice to identify possible boundary cap cell ligands, their receptors on motor neurons and cytoplasmic signalling molecules that control this process. Results We demonstrate that targeted knock down in motor neurons of Neuropilin-2 (Npn-2), a high affinity receptor for class 3 semaphorins, causes their somata to migrate to ectopic positions in ventral nerve roots. This finding was corroborated in Npn-2 null mice, in which we identified motor neuron cell bodies in ectopic positions in the PNS. Our RNA interference studies further revealed a role for Plexin-A2, but not Plexin-A1 or Plexin-A4. We show that chick and mouse boundary cap cells express Sema3B and 3G, secreted semaphorins, and Sema6A, a transmembrane semaphorin. However, no increased numbers of ectopic motor neurons are found in Sema3B null mouse embryos. In contrast, Sema6A null mice display an ectopic motor neuron phenotype. Finally, knockdown of MICAL3, a downstream semaphorin/Plexin-A signalling molecule, in chick motor neurons led to their ectopic positioning in the PNS. Conclusion We conclude that semaphorin-mediated repellent interactions between boundary cap cells and immature spinal motor neurons regulates somal positioning by countering the drag exerted on motor neuron cell bodies by their axons as they emerge from the CNS at motor exit points. Our data support a model in which BC cell semaphorins signal through Npn-2 and/or Plexin-A2 receptors on motor neurons via a cytoplasmic effector, MICAL3, to trigger cytoskeletal reorganisation. This leads to the disengagement of somal migration from axon extension and the confinement of motor neuron cell bodies to the spinal cord. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 30 Oct 2007 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238003 2007-10-30T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237995 Title: Proximal visceral endoderm and extraembryonic ectoderm regulate the formation of primordial germ cell precursors Authors: Chuva de Sousa Lopes, Susana M; Hayashi, Katsuhiko; Surani, M Azim Abstract: Abstract Background The extraembryonic tissues, visceral endoderm (VE) and extraembryonic ectoderm (ExE) are known to be important for the induction of primordial germ cells (PGCs) in mice via activation of the bone morphogenetic protein (BMP) signalling pathway. We investigated whether the VE and ExE have a direct role in the specification of PGCs, or in an earlier event, namely the induction of the PGC precursors in the proximal posterior epiblast cells. Results We cultured embryonic day (E) 5.75 to E7.0 mouse embryos in an explant-assay with or without extraembryonic tissues. The reconstituted pieces of embryonic and extraembryonic tissues were assessed for the formation of both PGC precursors and specified PGCs. For this, Blimp1:gfp and Stella:gfp transgenic mouse lines were used to distinguish between PGC precursors and specified PGC, respectively. We observed that the VE regulates formation of an appropriate number of PGC precursors between E6.25–E7.25, but it is not essential for the subsequent specification of PGCs from the precursor cells. Furthermore, we show that the ExE has a different role from that of the VE, which is to restrict localization of PGC precursors to the posterior part of the embryo. Conclusion We show that the VE and ExE have distinct roles in the induction of PGC precursors, namely the formation of a normal number of PGC precursors, and their appropriate localization during early development. However, these tissues do not have a direct role during the final stages of specification of the founder population of PGCs. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 20 Dec 2007 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237995 2007-12-20T00:00:00Z