Showing 41 - 50 of 116 Items

Date: 2023-01-01
Creator: Lucia Marie O'Sullivan
Access: Access restricted to the Bowdoin Community

Date: 2025-01-01
Creator: Samantha McLemore
Access: Access restricted to the Bowdoin Community
Date: 2013-10-01
Creator: Brendan Eliot Depue, Nick Ketz, Matthew V. Mollison, Erika Nyhus, Marie T. Banich, Tim Curran
Access: Open access
- Although investigations of memory and the dynamics of ERP components and neural oscillations as assessed through EEG have been well utilized, little research into the volitional nature of suppression over memory retrieval have used these methods. Oscillation analyses conducted on the Think/No-Think (TNT) task and volitional suppression of retrieval are of interest to broaden our knowledge of neural oscillations associated not only during successful memory retrieval but also when retrieval is unwanted or suppressed. In the current study, we measured EEG during a TNT task and performed ERP and EEG spectral power band analyses. ERP results replicated other researchers' observations of increases in 500-800 msec parietal effects for items where retrieval was instructed to be elaborated compared with being suppressed. Furthermore, EEG analyses indicated increased alpha (8-12 Hz) and theta (3-8 Hz) oscillations across parietal electrodes for items that were instructed to be suppressed versus those to be elaborated. Additionally, during the second half of the experiment (after repeated attempts at control), increases in theta oscillations were found across both frontal and parietal electrodes for items that were instructed to be suppressed and that were ultimately forgotten versus those ultimately remembered. Increased alpha power for items that were instructed to be suppressed versus elaborated may indicate reductions of retrieval attempts or lack of retrieval success. Increased theta power for items that were instructed to be suppressed versus elaborated may indicate increased or prolonged cognitive control to monitor retrieval events. © 2013 Massachusetts Institute of Technology.
Date: 2019-05-01
Creator: Katharine Torrey
Access: Open access
- The peptide vasotocin (VT) and its mammalian homologue, vasopressin (VP), produce effects on social behavior that are highly species- and context-specific. We recently sequenced two genes for V1a-like receptors (VTR) in the goldfish brain, one that encodes for a fully-functioning canonical receptor and one that encodes for a non-functional truncated receptor. The current study is an investigation of whether social context may alter expression of these receptor types and thus, potentially, behavioral responses to VT. We used western blotting and immunohistochemistry with custom anti-VTR antibodies to characterize the distribution of VTR throughout the forebrain and the hindbrain. Western blot results showed bands close to the predicted sizes for truncated and canonical VTR constructs, suggesting that both genes are translated into protein in the brain, but the presence of additional bands suggested potential nonspecific binding. Immunohistochemistry data revealed VTR signal throughout the brain in regions associated with social behavior. We additionally examined whether visual and olfactory context alters behavioral responsiveness to VT, potentially by altering the expression of one or both receptors. Behavioral tests suggested that VT inhibits approach to males, but its effect on response to females in reproductive contexts is still undetermined, likely due to interference from a stress response during testing. Further characterization of VTR throughout the brain will clarify how social context might alter VT signaling through context-dependent modulation of its receptors. Additionally, future work should examine the behavioral consequences of such modulation by further studying whether VT’s effect on social approach behavior depends on context.
Date: 2011-01-01
Creator: A. Forche, D. Abbey, T. Pisithkul, M. A. Weinzierl, T., Ringstrom, D. Bruck, K. Petersen, J. Berman
Access: Open access
- Genetic diversity is often generated during adaptation to stress, and in eukaryotes some of this diversity is thought to arise via recombination and reassortment of alleles during meiosis. Candida albicans, the most prevalent pathogen of humans, has no known meiotic cycle, and yet it is a heterozygous diploid that undergoes mitotic recombination during somatic growth. It has been shown that clinical isolates as well as strains passaged once through a mammalian host undergo increased levels of recombination. Here, we tested the hypothesis that stress conditions increase rates of mitotic recombination in C. albicans, which is measured as loss of heterozygosity (LOH) at specific loci. We show that LOH rates are elevated during in vitro exposure to oxidative stress, heat stress, and antifungal drugs. In addition, an increase in stress severity correlated well with increased LOH rates. LOH events can arise through local recombination, through homozygosis of longer tracts of chromosome arms, or by whole-chromosome homozygosis. Chromosome arm homozygosis was most prevalent in cultures grown under conventional lab conditions. Importantly, exposure to different stress conditions affected the levels of different types of LOH events, with oxidative stress causing increased recombination, while fluconazole and high temperature caused increases in events involving whole chromosomes. Thus, C. albicans generates increased amounts and different types of genetic diversity in response to a range of stress conditions, a process that we term "stress-induced LOH" that arises either by elevating rates of recombination and/or by increasing rates of chromosome missegregation. IMPORTANCE Stress-induced mutagenesis fuels the evolution of bacterial pathogens and is mainly driven by genetic changes via mitotic recombination. Little is known about this process in other organisms. Candida albicans, an opportunistic fungal pathogen, causes infections that require adaptation to different host environmental niches. We measured the rates of LOH and the types of LOH events that appeared in the absence and in the presence of physiologically relevant stresses and found that stress causes a significant increase in the rates of LOH and that this increase is proportional to the degree of stress. Furthermore, the types of LOH events that arose differed in a stress-dependent manner, indicating that eukaryotic cells generate increased genetic diversity in response to a range of stress conditions. We propose that this "stress-induced LOH" facilitates the rapid adaptation of C. albicans, which does not undergo meiosis, to changing environments within the host. © 2011 Forche et al.
Date: 2007-10-01
Creator: Alix Coste, Anna Selmecki, Anja Forche, Dorothée Diogo, Marie Elisabeth, Bougnoux, Christophe D'Enfert, Judith Berman, Dominique Sanglard
Access: Open access
- TAC1 (for transcriptional activator of CDR genes) is critical for the upregulation of the ABC transporters CDR1 and CDR2, which mediate azole resistance in Candida albicans. While a wild-type TAC1 allele drives high expression of CDR1/2 in response to inducers, we showed previously that TAC1 can be hyperactive by a gain-of-function (GOF) point mutation responsible for constitutive high expression of CDR1/2. High azole resistance levels are achieved when C. albicans carries hyperactive alleles only as a consequence of loss of heterozygosity (LOH) at the TAC1 locus on chromosome 5 (Chr 5), which is linked to the mating-type-like (MTL) locus. Both are located on the Chr 5 left arm along with ERG11 (target of azoles). In this work, five groups of related isolates containing azole-susceptible and -resistant strains were analyzed for the TAC1 and ERG11 alleles and for Chr 5 alterations. While recovered ERG11 alleles contained known mutations, 17 new TAC1 alleles were isolated, including 7 hyperactive alleles with five separate new GOF mutations. Single-nucleotide- polymorphism analysis of Chr 5 revealed that azole-resistant strains acquired TAC1 hyperactive alleles and, in most cases, ERG11 mutant alleles by LOH events not systematically including the MTL locus. TAC1 LOH resulted from mitotic recombination of the left arm of Chr 5, gene conversion within the TAC1 locus, or the loss and reduplication of the entire Chr 5. In one case, two independent TAC1 hyperactive alleles were acquired. Comparative genome hybridization and karyotype analysis revealed the presence of isochromosome 5L [i(5L)] in two azole-resistant strains. i(5L) leads to increased copy numbers of azole resistance genes present on the left arm of Chr 5, among them TAC1 and ERG11. Our work shows that azole resistance was due not only to the presence of specific mutations in azole resistance genes (at least ERG11 and TAC1) but also to their increase in copy number by LOH and to the addition of extra Chr 5 copies. With the combination of these different modifications, sophisticated genotypes were obtained. The development of azole resistance in C. albicans is therefore a powerful instrument for generating genetic diversity. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Date: 2019-05-01
Creator: Anja Forche, Norma V. Solis, Marc Swidergall, Robert Thomas, Alison, Guyer, Annette Beach, Gareth A. Cromie, Giang T. Le, Emily Lowell, Norman Pavelka, Judith Berman, Aimeé M. Dudley, Anna Selmecki, Scott G. Filler
Access: Open access
- When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invade oral epithelial cells and increased susceptibility to neutrophil killing. Whole genome sequencing of pre- and post-infection isolates found that the trisomies were usually maintained. Most post-infection isolates also contained de novo point mutations, but these were not conserved. While in vitro growth assays did not reveal phenotypes specific to de novo point mutations, they did reveal novel phenotypes specific to each lineage. These data reveal that during OPC, clones that are trisomic for Chr5 or Chr6 are selected and they facilitate a commensal-like phenotype.

Date: 2020-01-01
Creator: Julianne Scholes
Access: Access restricted to the Bowdoin Community
Date: 2018-02-13
Creator: Robert S. Ross, Andrew Smolen, Tim Curran, Erika Nyhus
Access: Open access
- A critical problem for developing personalized treatment plans for cognitive disruptions is the lack of understanding how individual differences influence cognition. Recognition memory is one cognitive ability that varies from person to person and that variation may be related to different genetic phenotypes. One gene that may impact recognition memory is the monoamine oxidase A gene (MAO-A), which influences the transcription rate of MAO-A. Examination of how MAO-A phenotypes impact behavioral and event-related potentials (ERPs) correlates of recognition memory may help explain individual differences in recognition memory performance. Therefore, the current study uses electroencephalography (EEG) in combination with genetic phenotyping of the MAO-A gene to determine how well-characterized ERP components of recognition memory, the early frontal old/new effect, left parietal old/new effect, late frontal old/new effect, and the late posterior negativity (LPN) are impacted by MAO-A phenotype during item and source memory. Our results show that individuals with the MAO-A phenotype leading to increased transcription have lower response sensitivity during both item and source memory. Additionally, during item memory the left parietal old/new effect is not present due to increased ERP amplitude for correct rejections. The results suggest that MAO-A phenotype changes EEG correlates of recognition memory and influences how well individuals differentiate between old and new items.
Date: 2009-08-04
Creator: Erika Nyhus, Tim Curran
Access: Open access
- The present experiments examined how semantic vs. perceptual encoding and perceptual match affect the processes involved in recognition memory. Experiment 1 examined the effects of encoding task and perceptual match between study and test fonts on recognition discrimination for words. Font fan was used to determine the effect of distinctiveness on perceptual match. The semantic encoding task and perceptual match for distinctive items led to better recognition memory. Event-related brain potentials (ERPs) recorded from the human scalp during recognition memory experiments have revealed differences between old (studied) and new (not studied) items that are thought to reflect the activity of memory-related brain processes. In Experiment 2, the semantic encoding task and perceptual match for distinctive words led to better recognition memory by acting on both familiarity and recollection processes, as purportedly indexed by the FN400 and parietal old/new effects. Combined these results suggest that the semantic encoding task and perceptual match for distinctive items aid recognition memory by acting on both familiarity and recollection processes. © 2009 Elsevier B.V. All rights reserved.