IMPACT OF ODORS ON PATERNAL RESPONSIVENESS AND ASSOCIATED NEURONAL ACTIVITY IN "EXPECTANT" MALE PRAIRIE VOLES (Microtus ochrogaster),
Year of Dissertation:
2011
Advisor:
Dr. Maryam Bamshad-Alavi
Prairie voles (Microtus ochrogaster) are unusual mammals because they are socially monogamous. The breeding pairs form pair bonds and jointly care for offspring. Although the duration and intensity of parental behavior in male prairie voles is similar to that observed in females, there are sex differences in the onset and pattern of infant caring in this species. The factors that contribute to sex differences in parental behavior of prairie voles are unknown. As males and females show all components of active and inactive parental behaviors, it is possible that sensory inputs from infants arouse a different pattern of parental care in each sex. Males and females may also differ in the degree of attentiveness to infant sensory cues and to other environmental stimuli. Furthermore, they may focus their attention on different aspects of infant cues or perceive the same cues differently. I conducted three experiments to test these hypotheses. In the first experiment, I tested the attentiveness and sensitivity of male and female prairie voles towards infant-related odors across the reproductive period. Males and females showed increased attentiveness to infant-related odors at different times during the reproductive period. In the second experiment, I examined the impact of female sensory cues on male responsiveness towards infant odors. The data suggest that male's exposure to the female's tactile and distal cues during the gestation period elicited indirect paternal behavior in presence of infant odors. However, infant odors alone were insufficient to stimulate direct paternal responsiveness in these males. In the third experiment, I studied the neuronal activity of brain areas that could be involved in the enhanced indirect paternal behavior that was observed in males housed with their mate through mid gestation. In response to infant-related odors, males that had stayed with their mate had higher neuronal activity in the ventral tegmental area (VTA) compared to males that had stayed with their same-sex sibling. Together, these studies indicate that female sensory cues in prairie voles play an important role in enhancing indirect paternal care by increasing the male's attentiveness to odors and activating neurons in the VTA region of his brain.
Lichen Taxonomy for the 21st Century: A Revision of the Genus Lepraria s.l. in North America north of Mexico
Year of Dissertation:
2012
The results of a series of studies of lichens are presented. These studies are hoped to codify a forward for taxonomic progress in the group. Chapter one presents a standardized morphological terminology and descriptive scheme for the sterile crustose genus Lepraria. Chapters two through seven present a series of studies where molecular phylogenetic analyses of nrITS sequence were used to resolve species boundaries in Cladonia (III), Lepraria (IV-VII), and Punctelia (II). Chapter eight reveals not all sterile crustose lichens resemble their congeners. Chapter nine presents a study in the use of molecular data to place an unknown sterile crustose lichen in higher level classification of fungi. Chapter ten uses that method to revise the circumscriptions of Lepraria and the sterile fruticose genus Leprocaulon. Finally, chapter eleven comprises a taxonomic revision of the crustose species of Lepraria s. str. that occur in North America north of Mexico.
Regulation of anti-dsDNA B-cells in mice transgenic for the heavy and light chains of an Anti-dsDNA antibody
Year of Dissertation:
2010
Regulation of anti-dsDNA B-cells in mice transgenic for the heavy and light chains of an Anti-dsDNA antibody
Characterization of the Sinorhizobium meliloti ExoR protein
Year of Dissertation:
2009
The soil bacterium Sinorhizobium meliloti is capable of establishing a symbiotic relationship with its leguminous plant host alfalfa by forming nitrogen-fixing root nodules through a series of signal exchanges and structural changes. The presence of a potential bacterial signal molecule, succinoglycan, is required for the invasion step of this symbiosis. The production of succinoglycan, which is inversely coupled with the production of flagella, is tightly regulated by the S. meliloti ExoR protein and the ExoS/ChvI two-component regulatory system. To better understand the regulatory function of ExoR and its relationship with the ExoS/ChvI system, I have carried out extensive genetic and biochemical analyses of ExoR and ExoS proteins. I found that ExoR is a periplasmic protein and it functions only in the periplasm. Interestingly, the C-terminal 20 amino acids appear not to be essential for the regulatory function of ExoR. Most importantly, the ExoR protein is digested in the periplasm, which appears to be the molecular mechanism regulating the amount of functional ExoR protein in the periplasm. The genetic analysis of my collection of exoR, exoS, and chvI mutants suggests that ExoR functions upstream of the ExoS/ChvI two-component signal transduction pathway. This conclusion was further supported by the analysis of the exoR expression in different genetic backgrounds, which suggests the ExoR-ExoS-ChvI pathway is feedback regulated by ExoR. The combination of biochemical and genetic analyses suggest that ExoR functions in the periplasm through interaction with the ExoS sensing domain to keep ExoS in the off state. The proteolysis of ExoR would reduce the amount of functional ExoR and lead to the activation of ExoS and the expression of the genes regulated by the pathway. With the continuous discovery of ExoR/ExoS/ChvI homologous systems in a wide range of bacteria, my findings will contribute to a better understanding of the S. meliloti-alfalfa symbiosis and the pathogenicity of some bacterial plant and animal pathogens.
Antimalarial Benzophenones and Xanthones from Garcinia species
Year of Dissertation:
2011
Garicina, a genus in the Clusiaceae, is a source of antiparasitic and antimalarial phenolic secondary metabolites, including benzophenones and xanthones. The methanolic extracts of G. livingstonei, G. mangostana, G. spicata, and G. xanthochymus were tested in vitro for antiplasmodial activity against the P. falciparum clone D6. The crude methanolic G. mangostana extract inhibited the clone by 89%, while the G. xanthochymus extract inhibited it by 24%. Neither of the extracts showed any cytotoxicity toward Vero cells. Hexanes, EtOAc, and n-BuOH partitions of a G. xanthochymus seed extract were also screened against the P. falciparum clone D6, the hexanes partition inhibited the clone by 58%, the EtOAc and n-BuOH partitions showed no inhibitory activity. Additionally, compounds identified from Garcinia species were screened in the plasmodial lactase dehydrogenase (pLDH) activity assay. The compounds tested were: aristophenone A (1), cycloxanthochymol (2), gambogenone (3), guttiferone A (4), guttiferone E (5), guttiferone H (6), isoxanthochymol (7), xantochymol (8), xanthone (9), mangiferin (10), alloathyriol (11), alpha-mangostin (12), beta-mangostin (13), 3-isomangostin (14), 8-desoxygartanin (15), 4-methoxyxanthone (16), 1,5,6-trihydroxyxanthone (17), and 32-hydroxy-ent-guttiferone M (18). Only compounds 5, 6, 7, 12, 13, and 14 showed antiplasmodial activity. The antiplasmodial activities of compounds 5, 6, and 14 have not been previously reported. This is the first report of 7, 12, and 13 having antiplasmodial activity against the chloroquine-sensitive P. falciparum clone D6 and chloroquine-resistant clone W2.
The Role of Soluble Adenylyl Cyclase in the BDNF-Dependent Block of MAG/Myelin-Mediated Inhibition
Year of Dissertation:
2010
In the adult mammalian central nervous system axons do not spontaneously regenerate following injury. This lack of axonal regeneration is partly due to the presence of inhibitory proteins, such as myelin-associated glycoprotein (MAG). Previously, we showed that elevating cyclic AMP (cAMP) by pretreating (priming) neurons with neurotrophins, such as brain-derived neurotrophic factor (BDNF), is sufficient to overcome the block of axonal outgrowth by MAG. Additionally, we demonstrated this BDNF-mediated effect to be PKA-, ERK-, calcium- and CREB-dependent. However, increasing cAMP levels in response to BDNF could be dependent on several factors. A balance between the production of cAMP by adenylyl cyclases and its degradation by PDEs will determine intracellular cAMP levels. Given that the source of the cAMP produced in response to BDNF is unknown, we sought to investigate which adenylyl cyclase is activated, transmembrane adenylyl cyclase (tmAC) or soluble adenylyl cyclase (sAC). tmACs and sAC differ in their spatial localization within the cell, structure and regulation. Our hypothesis is that the rise in cAMP in response to BDNF priming is partially dependent on sAC activation.
Systematics and Taxonomy of Solanum sections Dunaliana and Irenosolanum (Solanaceae)
Year of Dissertation:
2012
The monophyly and phylogenetic relationships of the Solanum dunalianum group have been the subject of controversy. The S. dunalianum group was investigated using fifty-eight morphological characters and DNA sequence data: molecular markers ITS, trnT-trnF, and waxy. The individual datasets, combined molecular dataset, and total evidence dataset were analyzed under the parsimony criterion. In all analyses, the S. dunalianum group was resolved as not monophyletic, necessitating taxonomic realignment. In the total evidence strict consensus, all species of the Solanum dunalianum group, except S. tetrandrum, fell into either of two clades, compatible with the previously proposed Solanum sections Dunaliana and Irenosolanum. Solanum tetrandrum was resolved with S. melongena indicating an affinity with species from tropical Asia. Solanum section Dunaliana was sister to New Guinean species of the S. ferocissimum group. Solanum section Irenosolanum was sister to a clade of Australian and New Guinean species of various groups. No unique synapomorphies support either section, but morphological trends exist. Taxonomic treatments for each section are presented. Both include a key to species, distribution maps, and images of type specimens. Solanum section Dunaliana, centered on New Guinea, is restricted to a morphologically coherent clade of six species including S. labyrinthinum named herein. It is characterized by a large shrub or small tree habit,
Influenza A and Flavivirus Manipulation of Cell Death
Year of Dissertation:
2011
Viruses employ a variety of strategies to manipulate cell fate and maximize their replication potential during infection. Interacting specifically with cell death pathways allows viruses direct control over the cellular decision to survive or die during infection.
Wild Oysters, Crassostrea virginica, in the Hudson River Estuary: Growth, Health and Population Structure
Year of Dissertation:
2010
It has been estimated that the Hudson River Estuary (HRE) once had 350 square miles of oyster beds. Overharvesting and pollution during the Industrial Age ultimately led to the near eradication of the species from the estuary. Oysters are known for their filtering effects in minimizing eutrophication and oyster reefs provide habitat to many species of fish, invertebrates and algae. Today, there are no known functional oyster reefs in the HRE, but individual oysters can be found attached to rock and other hard substrate along shorelines. Their distribution, abundance, growth, and health were unknown.
cAMP AND CHAPERONES: POTENTIAL THERAPEUTIC STRATEGIES TO PREVENT INFLAMMATION-LINKED TAU PATHOLOGY IN ALZHEIMER'S DISEASE
Author:
Maria Jose Metcalfe
Year of Dissertation:
2011
Advisor:
Maria Figueiredo-Pereira
Senile plaques and neurofibrillary tangles are hallmarks of Alzheimer's disease (AD). The main component of neurofibrillary tangles (NFTs) is Tau, a highly soluble microtubule-associated protein whose major function is to stabilize microtubules, specifically in axons, in a phosphorylation-dependent manner. Neurodegenerative diseases collectively designated "Tauopathies" are linked to Tau mutations and/or Tau post-translational modifications. Accordingly, Tau hyperphosphorylation and cleavage are important events leading to Tau intracellular accumulation, aggregation and neuronal cell death. Caspase-cleaved Tau is detected in NFTs supporting the view that the apoptosis cascade is involved in the formation of NFTs. It is thought that Tau cleavage at its C-terminus by caspases renders Tau prone to aggregation and formation of NFTs. At the sites of damage, AD brains also exhibit signs of chronic inflammation manifested by reactive astrocytes and microglia, which produce cytotoxic agents among them prostaglandins. There is a profound gap in our understanding of how cyclooxygenases and their prostaglandin products redirect cellular events to promote neurodegeneration.