123 research outputs found

    First person - Sonal

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    First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Sonal is the first author on ‘Myosin-II activity generates a dynamic steady state with continuous actin turnover in a minimal actin cortex’, published in Journal of Cell Science. Sonal conducted the research in this article while a PhD student in the lab of Petra Schwille at the Max Planck Institute of Biochemistry, Martinsried, Germany, studying biological pattern formation using a bottom-up reconstitution approach

    Effects of aerobic and anaerobic environments on bacterial mutation rates and mutation spectra assessed by whole genome analyses : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Genetics at Massey University, Palmerston North, New Zealand

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    For organisms that are exposed to different environments, the rates and types of spontaneous mutations that arise in each environment can vary, and potentially impact the direction of evolution as a whole. Oxidative stress is a major cause of mutation, but the effect of oxygen availability on the mutation rates and spectra of organisms grown in aerobic as compared to anaerobic environments is not well understood at the whole genome level. To investigate the mutation rates and spectra of a facultative anaerobic bacterium grown under strictly aerobic or anaerobic conditions, 24 mutation accumulation lineages, derived from Escherichia coli REL4536, were established and propagated through 180 and 144 single-colony population bottlenecks, respectively. Spontaneous mutation rates of 2.50 × 10-10 and 4.14 × 10-10 mutations per nucleotide per generation were obtained for aerobically and anaerobically grown cells, respectively. Mutations in the aerobic environment were significantly biased towards G T mutations and IS186 transposition, while C A, T G, A C mutations, gross chromosomal rearrangements (GCRs) and IS150 transposition were significantly more prevalent under anaerobic conditions. Transcriptional profiling, via RNAseq, of REL4536 grown under aerobic and anaerobic environments revealed that repair genes, especially those involved in the repair of GCRs, were generally up-regulated in the anaerobic environment, consistent with findings that mutation rates, especially for GCRs, are higher in the anaerobic environment. GCRs have long been thought to play an important role in the evolutionary process, though their contributions to the process have not been specifically defined. SbcCD, an exonuclease, is involved in the repair of DNA secondary structures, and is thought to help prevent the occurrence of GCRs. Transcriptome analyses showed that in E. coli, sbcC was up-regulated during growth in an anaerobic environment, as compared to an aerobic environment. To investigate the impact of GCRs on adaptive evolution, an E. coli REL4536 strain with disrupted sbcC was constructed and evolved under anaerobic conditions for 1,000 generations in glucose-limited media in 14 parallel populations. Mutations that arose during evolution were determined by whole genome re-sequencing of selected clones, and evolved sbcC mutant strains displayed more GCRs and enhanced population-level fitness on average. Together, these results suggest that GCRs may play an important role in the rate of adaptation

    Behavioral and physiological assessment of an animal model of post-traumatic stress disorder

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    Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by exposure to a traumatic event. Despite recent progress, the causes and pathophysiology of PTSD remain poorly understood, partly because of ethical limitations inherent to human studies. One approach to circumvent this obstacle is to study PTSD in a valid animal model of the human syndrome. In one such model, extreme and long-lasting behavioral manifestations of anxiety develop in a subset of Lewis rats after exposure to an intense predator threat (PT) that mimics the type of life-or-death situation known to precipitate PTSD in humans. Thus, the first half of this thesis tested whether the Lewis rat model reproduces salient features of human PTSD. The results of these studies established the model’s face validity. The second half of this thesis used this model to identify alterations in the physiological properties of amygdala neurons that underlie the expression of PTSD. These studies revealed that PTSD is associated with differences in the synaptic responsiveness of central amygdala (CeA) neurons. Overall, these results suggest that the Lewis rat model of PTSD can be used to gain mechanistic insights in the pathophysiology of PTSD.Ph.D.Includes bibliographical referencesIncludes vitaby Sonal Goswam

    From homeland to home: Widening Participation through the LEAP Macquarie Mentoring (Refugee Mentoring) Program

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    Mentoring is often conceptualised as a one-to-one interaction between peers, or as an academic to student interaction, with the aim of developing self-esteem, connectedness, identity, and academic attitudes within one party. While various researchers have provided support for effectiveness of mentoring in fostering the aforementioned qualities, limited studies have looked at the impacts of outreach mentoring programs. This article examines the impact of the LEAP-Macquarie Mentoring (Refugee Mentoring) program on high school students from refugee backgrounds who are mentees on the program and on the university students who are mentors on the program. A qualitative study was completed involving five focus groups, individual and semi structured interviews with 54 mentees and diary analysis of 45 mentors. Transcripts of interview and focus groups were analysed using a grounded approach. Key findings highlighted that the LEAP-Macquarie Mentoring (Refugee Mentoring) program supported both mentors and mentees in making a smooth personal, social, and academic transition from high school to university, helped them develop leadership potential, and provided them with a connection to community

    Investigating the role of radixin in modulation of stereocilia length and stiffness

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    Mammalian hearing depends on deflection of stereocilia on the sensory outer hair cells of the inner ear. Previous data indicate that the stiffness of outer hair cell stereocilia are actively regulated. The molecular mechanism that regulate the deflection of stereocilia are presently less known. The aim of the study is to investigate the mechanistic pathway that underlie the stiffness modulation of outer hair cell stereocilia. Our hypothesis is that the membrane-cytoskeleton linker protein radixin, which is present at high concentration in stereocilia, could contribute to stiffness regulation. To test this hypothesis, we use the radixin blocker DX-52-1 which binds strongly and specifically to radixin. Time-resolved confocal imaging was used to visualize the sound-evoked motion of stereocilia in a semi-intact preparation of the guinea pig temporal bone. Cochlear microphonic potentials were also measured, using electrodes positioned in scala media. We found that the DX-52-1 inhibitor leads to an increase in stereocilia movements and decline in the amplitude of the cochlear microphonic potential. However, DX-52-1 caused a paradoxical increase in electromotility. These results suggest that radixin has a functionally important regulatory role in the mature inner ear.</p

    Trade-off between ordinary differential equation and Legendre polynomial methods to study guided modes in angle-ply laminate

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    It has been shown that the roots of guided waves in laminate plates produced by the ordinary differential equations (ODE) approach may not hold under to some computational conditions. A particular drawback of the 2D formulation of the ODE approach is the lack of reliability in the case of unidirectional laminates due to the decoupling properties between the SH and Lamb wave modes, which is caused by the unified matrix of roots. Due to this problem, the SH modes disappear from the unified roots of guided modes, then re-emerge with a separate computation of the SH and Lamb wave modes. Initially, we did not notice this computational “bug” in the event of a coupling between the SH and Lamb wave modes. In this context, the Legendre polynomial method is used to illustrate that fact. Results demonstrate how the polynomial method is pre-eminent to handle the laminate modelling over the ODE method for these specific requirements, however, a trade-off between these two methods needs to be considered to obtain stable and robust behavior of guided dispersion curves. This short study ends with conclusions and future perspectives.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Structural Integrity & Composite

    Enhanced Software Effort Estimation Using Multi Layered Feed Forward Artificial Neural Network Technique

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    AbstractSoftware Effort Estimation models are hot topic of study over 3 decades. Several models have been developed in these decades. Providing accurate estimations of software is still very challenging. The major reason for such disappointments in projects are because of inaccurate software development norms; effort estimation is one such practice. Dynamically fluctuating environment of technology in software development industry make effort estimation further perplexing. One of the most commonly used algorithmic model for estimating effort in industry is COCOMO. Capability of machine learning particularly Artificial Neural Networks is to adjust a complex set of bond among the various independent and dependent variables. The paper proposes usage of ANN (Artificial Neural Network) based model technologically advanced using Multi Layered Feed Forward Neural Network which is given training with Back Propagation training method. COCOMO data-set is accustomed to test and train the network. Mean-Square-Error (MSE) and Mean Magnitude of Relative-Error (MMRE) are used as performance measurement indices. The experiment outputs suggest that the suggested model can provide better results and accurately forecast the software development effort

    Dynamics and genetic diversification of Escherichia coli during experimental adaptation to an anaerobic environment

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    Background Many bacteria are facultative anaerobes, and can proliferate in both anoxic and oxic environments. Under anaerobic conditions, fermentation is the primary means of energy generation in contrast to respiration. Furthermore, the rates and spectra of spontaneous mutations that arise during anaerobic growth differ to those under aerobic growth. A long-term selection experiment was undertaken to investigate the genetic changes that underpin how the facultative anaerobe, Escherichia coli, adapts to anaerobic environments. Methods Twenty-one populations of E. coli REL4536, an aerobically evolved 10,000th generation descendent of the E. coli B strain, REL606, were established from a clonal ancestral culture. These were serially sub-cultured for 2,000 generations in a defined minimal glucose medium in strict aerobic and strict anaerobic environments, as well as in a treatment that fluctuated between the two environments. The competitive fitness of the evolving lineages was assessed at approximately 0, 1,000 and 2,000 generations, in both the environment of selection and the alternative environment. Whole genome re-sequencing was performed on random colonies from all lineages after 2,000-generations. Mutations were identified relative to the ancestral genome, and based on the extent of parallelism, traits that were likely to have contributed towards adaptation were inferred. Results There were increases in fitness relative to the ancestor among anaerobically evolved lineages when tested in the anaerobic environment, but no increases were found in the aerobic environment. For lineages that had evolved under the fluctuating regime, relative fitness increased significantly in the anaerobic environment, but did not increase in the aerobic environment. The aerobically-evolved lineages did not increase in fitness when tested in either the aerobic or anaerobic environments. The strictly anaerobic lineages adapted more rapidly to the anaerobic environment than did the fluctuating lineages. Two main strategies appeared to predominate during adaptation to the anaerobic environment: modification of energy generation pathways, and inactivation of non-essential functions. Fermentation pathways appeared to alter through selection for mutations in genes such as nadR, adhE, dcuS/R, and pflB. Mutations were frequently identified in genes for presumably dispensable functions such as toxin-antitoxin systems, prophages, virulence and amino acid transport. Adaptation of the fluctuating lineages to the anaerobic environments involved mutations affecting traits similar to those observed in the anaerobically evolved lineages. Discussion There appeared to be strong selective pressure for activities that conferred cell yield advantages during anaerobic growth, which include restoring activities that had previously been inactivated under long-term continuous aerobic evolution of the ancestor

    Dynamics and genetic diversification of Escherichia coli during experimental adaptation to an anaerobic environment

    No full text
    Background. Many bacteria are facultative anaerobes, and can proliferate in both anoxic and oxic environments. Under anaerobic conditions, fermentation is the primary means of energy generation in contrast to respiration. Furthermore, the rates and spectra of spontaneous mutations that arise during anaerobic growth differ to those under aerobic growth. A long-term selection experiment was undertaken to investigate the genetic changes that underpin how the facultative anaerobe, Escherichia coli, adapts to anaerobic environments. Methods. Twenty-one populations of E. coli REL4536, an aerobically evolved 10,000th generation descendent of the E. coli B strain, REL606, were established from a clonal ancestral culture. These were serially sub-cultured for 2,000 generations in a defined minimal glucose medium in strict aerobic and strict anaerobic environments, as well as in a treatment that fluctuated between the two environments. The competitive fitness of the evolving lineages was assessed at approximately 0, 1,000 and 2,000 generations, in both the environment of selection and the alternative environment. Whole genome re-sequencing was performed on random colonies from all lineages after 2,000-generations. Mutations were identified relative to the ancestral genome, and based on the extent of parallelism, traits that were likely to have contributed towards adaptation were inferred. Results. There were increases in fitness relative to the ancestor among anaerobically evolved lineages when tested in the anaerobic environment, but no increases were found in the aerobic environment. For lineages that had evolved under the fluctuating regime, relative fitness increased significantly in the anaerobic environment, but did not increase in the aerobic environment. The aerobically-evolved lineages did not increase in fitness when tested in either the aerobic or anaerobic environments. The strictly anaerobic lineages adapted more rapidly to the anaerobic environment than did the fluctuating lineages. Two main strategies appeared to predominate during adaptation to the anaerobic environment: modification of energy generation pathways, and inactivation of non-essential functions. Fermentation pathways appeared to alter through selection for mutations in genes such as nadR, adhE, dcuS/R, and pflB. Mutations were frequently identified in genes for presumably dispensable functions such as toxin-antitoxin systems, prophages, virulence and amino acid transport. Adaptation of the fluctuating lineages to the anaerobic environments involved mutations affecting traits similar to those observed in the anaerobically evolved lineages. Discussion. There appeared to be strong selective pressure for activities that conferred cell yield advantages during anaerobic growth, which include restoring activities that had previously been inactivated under long-term continuous aerobic evolution of the ancestor
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