Showing 91 - 100 of 106 Items
Mechanisms underlying variable responses to isoforms of the neuropeptide C-type allatostatin (AST-C) in the cardiac neuromuscular system of the American lobster, Homarus americanus
Date: 2019-01-01
Creator: Evalyn Mackenzie
Access: Open access
- Central Pattern Generators (CPGs) are neural networks that produce steady, rhythmic patterned outputs that activate particular muscles and consequently create recurrent rhythmic movements. The cardiac ganglion (CG) of the American lobster (Homarus americanus) is a useful model system for the study of CPGs. Neuropeptides modulate cardiac contractions driven by the CG in H. americanus and accordingly elicit a range of effects. Post-translational modifications such as amidation can impact function of a peptide neuromodulator. C-type allatostatins (AST-Cs) are a group of neuropeptides that modulate the cardiac neuromuscular system of H. americanus. The objective of this study was to determine what structural aspects of the peptides were responsible for the similarity in responses elicited by AST-C I and AST-C III and the difference in responses evoked by AST-C II in comparison. AST-C I and AST-C III are not C-terminally amidated, whereas AST-C II is C-terminally amidated. We first hypothesized that amidated AST-C peptides would evoke similar responses to one another in contraction amplitude and frequency. Our second hypothesis was that exchanging the amino acids alanine and tyrosine at a specific location in AST-C II and AST-C III would affect the conformation of the peptide, and consequently impact peptide binding and elicit different effects. In contrast to our predictions, we did not see similar responses evoked by all amidated or all non-amidated peptides among lobsters. In support of our second hypothesis, there was a significant difference in percent change in contraction amplitude elicited among AST-C II Y, AST-C II and AST-C III.
The effects of manipulated afterload pressure on heartbeat frequency, active force, and cardiac output of the American lobster, Homarus americanus Access to this record is restricted to members of the Bowdoin community. Log in here to view.
Date: 2019-05-01
Creator: Gina Fickera
Access: Access restricted to the Bowdoin Community
Rapid mechanisms for generating genome diversity: Whole ploidy shifts, aneuploidy, and loss of heterozygosity
Date: 2014-01-01
Creator: Richard J. Bennett, Anja Forche, Judith Berman
Access: Open access
- Human fungal pathogens can exist in a variety of ploidy states, including euploid and aneuploid forms. Ploidy change has a major impact on phenotypic properties, including the regulation of interactions with the human host. In addition, the rapid emergence of drug-resistant isolates is often associated with the formation of specific supernumerary chromosomes. Pathogens such as Candida albicans and Cryptococcus neoformans appear particularly well adapted for propagation in multiple ploidy states with novel pathways driving ploidy variation. In both species, heterozygous cells also readily undergo loss of heterozygosity (LOH), leading to additional phenotypic changes such as altered drug resistance. Here, we examine the sexual and parasexual cycles that drive ploidy variation in human fungal pathogens and discuss ploidy and LOH events with respect to their far-reaching roles in fungal adaptation and pathogenesis.
The 'obligate diploid' Candida albicans forms mating-competent haploids
Date: 2013-02-07
Creator: Meleah A. Hickman, Guisheng Zeng, Anja Forche, Matthew P. Hirakawa, Darren, Abbey, Benjamin D. Harrison, Yan Ming Wang, Ching Hua Su, Richard J. Bennett, Yue Wang, Judith Berman
Access: Open access
- Candida albicans, the most prevalent human fungal pathogen, is considered to be an obligate diploid that carries recessive lethal mutations throughout the genome. Here we demonstrate that C. albicans has a viable haploid state that can be derived from diploid cells under in vitro and in vivo conditions, and that seems to arise through a concerted chromosome loss mechanism. Haploids undergo morphogenetic changes like those of diploids, including the yeast-hyphal transition, chlamydospore formation and a white-opaque switch that facilitates mating. Haploid opaque cells of opposite mating type mate efficiently to regenerate the diploid form, restoring heterozygosity and fitness. Homozygous diploids arise spontaneously by auto-diploidization, and both haploids and auto-diploids show a similar reduction in fitness, in vitro and in vivo, relative to heterozygous diploids, indicating that homozygous cell types are transient in mixed populations. Finally, we constructed stable haploid strains with multiple auxotrophies that will facilitate molecular and genetic analyses of this important pathogen. © 2013 Macmillan Publishers Limited. All rights reserved.
Genome plasticity in candida albicans is driven by long repeat sequences
Date: 2019-06-01
Creator: Robert T. Todd, Tyler D. Wikoff, Anja Forche, Anna Selmecki
Access: Open access
- Genome rearrangements resulting in copy number variation (CNV) and loss of heterozygosity (LOH) are frequently observed during the somatic evolution of cancer and promote rapid adaptation of fungi to novel environments. In the human fungal pathogen Candida albicans, CNV and LOH confer increased virulence and antifungal drug resistance, yet the mechanisms driving these rearrangements are not completely understood. Here, we unveil an extensive array of long repeat sequences (65–6499 bp) that are associated with CNV, LOH, and chromosomal inversions. Many of these long repeat sequences are uncharacterized and encompass one or more coding sequences that are actively transcribed. Repeats associated with genome rearrangements are predominantly inverted and separated by up to ~1.6 Mb, an extraordinary distance for homology-based DNA repair/recombination in yeast. These repeat sequences are a significant source of genome plasticity across diverse strain backgrounds including clinical, environmental, and experimentally evolved isolates, and represent previously uncharacterized variation in the reference genome.
Homozygosity at the MTL locus in clinical strains of Candida albicans: Karyotypic rearrangments and tetraploid formation
Date: 2004-06-01
Creator: Melanie Legrand, Paul Lephart, Anja Forche, Frank Michael C. Mueller, T., Walsh, P. T. Magee, Beatrice B. Magee
Access: Open access
- One hundred and twenty Candida albicans clinical isolates from the late 1980s and early 1990s were examined for homosygosity at the MTL locus. Of these, 108 were heterozygous (MTLa/MTLα), whereas seven were MTLa and five were MTLα. Five of the homozygous isolates were able to switch to the opaque cell morphology, while opaque cells were not detectable among the remaining seven. Nevertheless, all but one of the isolates homozygous at the MTL locus were shown to mate and to yield cells containing markers from both parents; the non-mater was found to have a frameshift in the MTLα1 gene. In contrast to Saccharomyces cerevisiae, C. albicans homozygotes with no active MTL allele failed to mate rather than mating as a cells. There was no correlation between homoxygosity and fluconazole resistance, mating and fluconazole resistance or switching and fluconazole resistance, in part because most of the strains were isolated before the widespread use of this antifungal agent, and only three were in fact drug resistant Ten of the 12 homozygotes had rearranged karyotypes involving one or more homologue of chromosomes 4, 5, 6 and 7. We suggest that karyotypic rearrangement, drug resistance and homozygosity come about as the result of induction of hyperrecombination during the infection process; hence, they tend to occur together, but each is the independent result of the same event. Furthermore, as clinical strains can mate and form tetraploids, mating and marker exchange are likely to be a significant part of the life cycle of C. albicans in vivo.
Individual differences in EEG correlates of recognition memory due to DAT polymorphisms
Date: 2017-12-01
Creator: Paolo Medrano, Erika Nyhus, Andrew Smolen, Tim Curran, Robert S., Ross
Access: Open access
- Introduction: Although previous research suggests that genetic variation in dopaminergic genes may affect recognition memory, the role dopamine transporter expression may have on the behavioral and EEG correlates of recognition memory has not been well established. Objectives: The study aims to reveal how individual differences in dopaminergic functioning due to genetic variations in the dopamine transporter gene influences behavioral and EEG correlates of recognition memory. Methods: Fifty-eight participants performed an item recognition task. Participants were asked to retrieve 200 previously presented words while brain activity was recorded with EEG. Regions of interest were established in scalp locations associated with recognition memory. Mean ERP amplitudes and event-related spectral perturbations when correctly remembering old items (hits) and recognizing new items (correct rejections) were compared as a function of dopamine transporter group. Results: Participants in the dopamine transporter group that codes for increased dopamine transporter expression (10/10 homozygotes) display slower reaction times compared to participants in the dopamine transporter group associated with the expression of fewer dopamine transporters (9R-carriers). 10/10 homozygotes further displayed differences in ERP and oscillatory activity compared to 9R-carriers. 10/10 homozygotes fail to display the left parietal old/new effect, an ERP signature of recognition memory associated with the amount of information retrieved. 10/10 homozygotes also displayed greater decreases of alpha and beta oscillatory activity during item memory retrieval compared to 9R-carriers. Conclusion: Compared to 9R-carriers, 10/10 homozygotes display slower hit and correct rejection reaction times, an absence of the left parietal old/new effect, and greater decreases in alpha and beta oscillatory activity during recognition memory. These results suggest that dopamine transporter polymorphisms influence recognition memory.
Incorporating an ERP project into undergraduate instruction
Date: 2016-01-01
Creator: Erika Nyhus, Nancy Curtis
Access: Open access
- Electroencephalogram (EEG) is a relatively non-invasive, simple technique, and recent advances in open source analysis tools make it feasible to implement EEG as a component in undergraduate neuroscience curriculum. We have successfully led students to design novel experiments, record EEG data, and analyze event-related potentials (ERPs) during a one-semester laboratory course for undergraduates in cognitive neuroscience. First, students learned how to set up an EEG recording and completed an analysis tutorial. Students then learned how to set up a novel EEG experiment; briefly, they formed groups of four and designed an EEG experiment on a topic of their choice. Over the course of two weeks students collected behavioral and EEG data. Each group then analyzed their behavioral and ERP data and presented their results both as a presentation and as a final paper. Upon completion of the group project students reported a deeper understanding of cognitive neuroscience methods and a greater appreciation for the strengths and weaknesses of the EEG technique. Although recent advances in open source software made this project possible, it also required access to EEG recording equipment and proprietary software. Future efforts should be directed at making publicly available datasets to learn ERP analysis techniques and making publicly available EEG recording and analysis software to increase the accessibility of hands-on research experience in undergraduate cognitive neuroscience laboratory courses. Copyright
Aneuploid chromosomes are highly unstable during DNA transformation of candida albicans∇
Date: 2009-10-01
Creator: Kelly Bouchonville, Anja Forche, Karen E.S. Tang, Anna Selmecki, Judith, Berman
Access: Open access
- Candida albicans strains tolerate aneuploidy, historically detected as karyotype alterations by pulsed-fleld gel electrophoresis and more recently revealed by array comparative genome hybridization, which provides a comprehensive and detailed description of gene copy number. Here, we first retrospectively analyzed 411 expression array experiments to predict the frequency of aneuploidy in different strains. As expected, significant levels of aneuploidy were seen in strains exposed to stress conditions, including UV light and/or sorbose treatment, as well as in strains that are resistant to antifungal drugs. More surprisingly, strains that underwent transformation with DNA displayed the highest frequency of chromosome copy number changes, with strains that were initially aneuploid exhibiting ∼3-fold more copy number changes than strains that were initially diploid. We then prospectively analyzed the effect of lithium acetate (LiOAc) transformation protocols on the stability of trisomie chromosomes. Consistent with the retrospective analysis, the proportion of karyotype changes was highly elevated in strains carrying aneuploid chromosomes. We then tested the hypothesis that stresses conferred by heat and/or LiOAc exposure promote chromosome number changes during DNA transformation procedures. Indeed, a short pulse of very high temperature caused frequent gains and losses of multiple chromosomes or chromosome segments. Furthermore, milder heat exposure over longer periods caused increased levels of loss of heterozygosity. Nonetheless, aneuploid chromosomes were also unstable when strains were transformed by electroporation, which does not include a heat shock step. Thus, aneuploid strains are particularly prone to undergo changes in chromosome number during the stresses of DNA transformation protocols. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Dendrites of Cardiac Ganglion Regulate Heartbeat of American Lobster, Homarus americanus, Through Stretch Feedback
Date: 2014-05-01
Creator: Mara R Chin-Purcell
Access: Open access
- Central pattern generators are neuronal networks that produce reliable rhythmic motor output. A simple pattern generator, known as the cardiac ganglion (CG), controls the heart of the American lobster, Homarus americanus. Previous studies have suggested that stretch feedback relays information to the cardiac ganglion about the degree of filling in the heart, and that this feedback is mediated by stretch-sensitive dendrites extending from CG neurons. I sought to determine the mechanisms behind this stretch feedback pathway. One hundred second extension pyramids were applied to each heart while amplitude and frequency of contractions were recorded; 87% of hearts responded to stretch with a significant increase in frequency of contractions. To ascertain the role of dendrites in this feedback pathway, the accessible branches along the trunk of the CG were severed, de-afferenting the CG. In de-afferented hearts, stretch sensitivity was significantly less than in intact hearts, suggesting that the dendrites extending from the CG are essential for carrying stretch feedback information. To separate the effects of active and passive forces of heart contraction on stretch sensitivity, the CG was de-efferented by severing the motor nerves that induce muscle contraction. Hearts with only anterolateral nerves cut or with all four efferents cut were significantly less stretch sensitive than controls. These results indicate that the CG is sensitive to active stretch of each contraction. Hearts with reduced stretch feedback had more irregular frequency of contractions, indicating that a role of stretch feedback in the cardiac system may be to maintain a regular heart rate.