Showing 91 - 100 of 116 Items
The Current Hunt for Nitric Oxide's Effects on the Homarus americanus Cardiac Ganglion
Date: 2022-01-01
Creator: Joanna Lin
Access: Open access
- The crustacean heartbeat is produced and modulated by the cardiac ganglion (CG), a central pattern generator. In the American lobster, Homarus americanus, the CG consists of 4 small premotor cells (SCs) that electrically and chemically synapse onto 5 large motor cells (LCs). Rhythmic driver potentials in the SCs generate bursting in the LCs, which elicit downstream cardiac muscle contractions that are essential for physiological functions. Endogenous neuromodulators mediate changes in the CG to meet homeostatic demands caused by environmental stressors. Nitric oxide (NO), a gaseous neuromodulator, inhibits the lobster CG. Heart contractions release NO, which directly decreases the CG burst frequency and indirectly decreases the heartbeat amplitude, to mediate negative feedback. I investigated NO’s inhibitory effects on the CG to further understand the mechanisms underlying intrinsic feedback. Using extracellular recordings, I examined NO modulation of the SCs and LCs when coupled in the intact circuit and when firing independently in the ligatured preparation. Using two-electrode voltage clamp, I additionally analyzed the modulation of channel kinetics. Based on previous studies, I hypothesized that NO decreases the burst frequency of the LCs and SCs by modulating conductance properties of the voltage-gated A-type potassium current (IA). My data showed that NO decreased the burst frequency in the LCs and the burst duration in the SCs in a state-dependent manner. Furthermore, NO increased the IA inactivation time constant to decrease the LCs’ burst frequency. Thus, NO mediated inhibitory effects on cardiac output by differentially targeting both cell types and altering the IA current kinetics.
Modulation of ionic currents by nitric oxide negative feedback in the lobster cardiac ganglion Access to this record is restricted to members of the Bowdoin community. Log in here to view.
- Restriction End Date: 2026-06-01
Date: 2021-01-01
Creator: Emily Renee King
Access: Access restricted to the Bowdoin Community
Attentional Inhibition of a Distractor on Memory Facilitation Access to this record is restricted to members of the Bowdoin community. Log in here to view.
Date: 2016-05-01
Creator: Jacob M MacDonald
Access: Access restricted to the Bowdoin Community
Efficacy of Curcumin as a Neuroprotectant Against Dibutyl Phthalate (DBP) - Induced Effects on the Mammalian Spinal Cord Locomotor Neural Network This record is embargoed.
- Embargo End Date: 2027-05-15
Date: 2024-01-01
Creator: Eliza Schotten
Access: Embargoed
The modulation of calcium-activated potassium channels for the stabilization of mammalian spinal locomotor activity This record is embargoed.
- Embargo End Date: 2026-12-14
Date: 2023-01-01
Creator: Hattie Sargent Slayton
Access: Embargoed
Genetic variation in the serotonin transporter gene influences ERP old/new effects during recognition memory
Date: 2015-11-01
Creator: Robert S. Ross, Paolo Medrano, Kaitlin Boyle, Andrew Smolen, Tim Curran, Erika Nyhus
Access: Open access
- Recognition memory is defined as the ability to recognize a previously encountered stimulus and has been associated with spatially and temporally distinct event-related potentials (ERPs). Allelic variations of the serotonin transporter gene (SLC6A4) have recently been shown to impact memory performance. Common variants of the serotonin transporter-linked polymorphic region (5HTTLPR) of the SLC6A4 gene result in long (l) and short (s) allelic variants with carriers of the s allele having lowered transcriptional efficiency. Thus, the current study examines the effects polymorphisms of the SLC6A4 gene have on performance and ERP amplitudes commonly associated with recognition memory. Electroencephalogram (EEG), genetic, and behavioral data were collected from sixty participants as they performed an item and source memory recognition task. In both tasks, participants studied and encoded 200 words, which were then mixed with 200 new words during retrieval. Participants were monitored with EEG during the retrieval portion of each memory task. EEG electrodes were grouped into four ROIs, left anterior superior, right anterior superior, left posterior superior, and right posterior superior. ERP mean amplitudes during hits in the item and source memory task were compared to correctly recognizing new items (correct rejections). Results show that s-carriers have decreased mean hit amplitudes in both the right anterior superior ROI 1000-1500. ms post stimulus during the source memory task and the left anterior superior ROI 300-500. ms post stimulus during the item memory task. These results suggest that individual differences due to genetic variation of the serotonin transporter gene influences recognition memory. © 2015 Elsevier Ltd.
An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1
Date: 2008-05-01
Creator: Anna Selmecki, Maryam Gerami-Nejad, Carsten Paulson, Anja Forche, Judith, Berman
Access: Open access
- Acquired azole resistance is a serious clinical problem that is often associated with the appearance of aneuploidy and, in particular, with the formation of an isochromosome [i(5L)] in the fungal opportunist Candida albicans. Here we exploited a series of isolates from an individual patient during the rapid acquisition of fluconazole resistance (FluR). Comparative genome hybridization arrays revealed that the presence of two extra copies of Chr5L, on the isochromosome, conferred increased FluR and that partial truncation of Chr5L reduced FluR. In vitro analysis of the strains by telomere-mediated truncations and by gene deletion assessed the contribution of all Chr5L genes and of four specific genes. Importantly, ERG11 (encoding the drug target) and a hyperactive allele of TAC1 (encoding a transcriptional regulator of drug efflux pumps) made independent, additive contributions to FluR in a gene copy number-dependent manner that was not different from the contributions of the entire Chr5L arm. Thus, the major mechanism by which i(5L) formation causes increased azole resistance is by amplifying two genes: ERG11 and TAC1. © 2008 The Authors.
Partner choice in spontaneous mitotic recombination in wild type and homologous recombination mutants of Candida albicans
Date: 2019-11-01
Creator: Alberto Bellido, Toni Ciudad, Belén Hermosa, Encarnación Andaluz, Anja, Forche, Germán Larriba
Access: Open access
- Candida albicans, the most common fungal pathogen, is a diploid with a genome that is rich in repeats and has high levels of heterozygosity. To study the role of different recombination pathways on direct-repeat recombination, we replaced either allele of the RAD52 gene (Chr6) with the URA-blaster cassette (hisG-URA3-hisG), measured rates of URA3 loss as resistance to 5-fluoroorotic acid (5FOAR) and used CHEF Southern hybridization and SNP-RFLP analysis to identify recombination mechanisms and their frequency in wildtype and recombination mutants. FOAR rates varied little across different strain backgrounds. In contrast, the type and frequency of mechanisms underlying direct repeat recombination varied greatly. For example, wildtype, rad59 and lig4 strains all displayed a bias for URA3 loss via pop-out/deletion vs. inter-homolog recombination and this bias was reduced in rad51 mutants. In addition, in rad51-derived 5FOAR strains direct repeat recombination was associated with ectopic translocation (5%), chromosome loss/truncation (14%) and inter-homolog recombination (6%). In the absence of RAD52, URA3 loss was mostly due to chromosome loss and truncation (80–90%), and the bias of retained allele frequency points to the presence of a recessive lethal allele on Chr6B. However, a few single-strand annealing (SSA)-like events were identified and these were independent of either Rad59 or Lig4. Finally, the specific sizes of Chr6 truncations suggest that the inserted URA-blaster could represent a fragile site.
A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans
Date: 2006-04-01
Creator: Alix Coste, Vincent Turner, Françoise Ischer, Joachim Morschhäuser, Anja, Forche, Anna Selmecki, Judith Berman, Jacques Bille, Dominique Sanglard
Access: Open access
- TAC1, a Candida albicans transcription factor situated near the mating-type locus on chromosome 5, is necessary for the upregulation of the ABC-transporter genes CDR1 and CDR2, which mediate azole resistance. We showed previously the existence of both wild-type and hyperactive TAC1 alleles. Wild-type alleles mediate upregulation of CDR1 and CDR2 upon exposure to inducers such as fluphenazine, while hyperactive alleles result in constitutive high expression of CDR1 and CDR2. Here we recovered TAC1 alleles from two pairs of matched azole-susceptible (DSY294; FH1: heterozygous at mating-type locus) and azole-resistant isolates (DSY296; FH3: homozygous at mating-type locus). Two different TAC1 wild-type alleles were recovered from DSY294 (TAC1-3 and TAC1-4) while a single hyperactive allele (TAC1-5) was isolated from DSY296. A single amino acid (aa) difference between TAC1-4 and TAC1-5 (Asn977 to Asp or N977D) was observed in a region corresponding to the predicted activation domain of Tac1p. Two TAC1 alleles were recovered from FH1 (TAC1-6 and TAC1-7) and a single hyperactive allele (TAC1-7) was recovered from FH3. The N977D change was seen in TAC1-7 in addition to several other aa differences. The importance of N977D in conferring hyperactivity to TAC1 was confirmed by site-directed mutagenesis. Both hyperactive alleles TAC1-5 and TAC1-7 were codominant with wild-type alleles and conferred hyperactive phenotypes only when homozygous. The mechanisms by which hyperactive alleles become homozygous was addressed by comparative genome hybridization and single nucleotide polymorphism arrays and indicated that loss of TAC1 heterozygosity can occur by recombination between portions of chromosome 5 or by chromosome 5 duplication. Copyright © 2006 by the Genetics Society of America.
Demonstration of loss of heterozygosity by single-nucleotide polymorphism microarray analysis and alterations in strain morphology in Candida albicans strains during infection
Date: 2005-01-01
Creator: Anja Forche, Georgiana May, P. T. Magee
Access: Open access
- Candida albicans is a diploid yeast with a predominantly clonal mode of reproduction, and no complete sexual cycle is known. As a commensal organism, it inhabits a variety of niches in humans. It becomes an opportunistic pathogen in immunocompromised patients and can cause both superficial and disseminated infections. It has been demonstrated that genome rearrangement and genetic variation in isolates of C. albicans are quite common. One possible mechanism for generating genome-level variation among individuals of this primarily clonal fungus is mutation and mitotic recombination leading to loss of heterozygosity (LOH). Taking advantage of a recently published genome-wide single-nucleotide polymorphism (SNP) map (A. Forche, P. T. Magee, B. B. Magee, and G. May, Eukaryot. Cell 3:705-714, 2004), an SNP microarray was developed for 23 SNP loci residing on chromosomes 5, 6, and 7. It was used to examine 21 strains previously shown to have undergone mitotic recombination at the GAL1 locus on chromosome 1 during infection in mice. In addition, karyotypes and morphological properties of these strains were evaluated. Our results show that during in vivo passaging, LOH events occur at observable frequencies, that such mitotic recombination events occur independently in different loci across the genome, and that changes in karyotypes and alterations of phenotypic characteristics can be observed alone, in combination, or together with LOH.