Thesis (Ph. D.)--University of Wisconsin--Madison, 1963. / Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 82-86).

Influenza infection remains a constant threat to human health and results in huge financial loss annually. Rapid and accurate detection of influenza can aid health officials to monitor influenza activity and take measurements when necessary. In addition, influenza detection in a timely manner can help doctors make diagnosis and provide effective treatment. Additionally, novel inhibitors of influenza virus are in high demand because circulating strains have started to develop resistance to currently available anti-viral drugs. Influenza virus has two surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA), which play important roles in the influenza infection. The binding of HA to sialic acid-containing carbohydrates on cell surface initiates virus internalization, while cleavage of terminal sialic acid by NA facilitates viral particle release. In this dissertation, we focus on the development of a glycan microarray that is comprised of a panel of NA resistant sialosides, and demonstrate the application of the microarray to capture influenza virus at ambient temperature without the addition of NA inhibitors. We also describe a novel electrochemical assay for the detection of influenza virus. In addition, we have developed a new class of bivalent NA inhibitors that show promising inhibitory activities against influenza viruses.

abstract: The failure to withhold inappropriate behavior is a central component of most impulse control disorders, including Attention Deficit Hyperactivity Disorder (ADHD). The present study examined the effects of housing environment and methylphenidate (a drug often prescribed for ADHD) on the performance of rats in two response inhibition tasks: differential reinforcement of low rate (DRL) and fixed minimum interval (FMI). Both tasks required rats to wait a fixed amount of time (6 s) before emitting a reinforced response. The capacity to withhold the target response (volitional inhibition) and timing precision were estimated on the basis of performance in each of the tasks. Paradoxically, rats housed in a mildly enriched environment that included a conspecific displayed less volitional inhibition in both tasks compared to rats housed in an isolated environment. Enriched housing, however, increased timing precision. Acute administration of methylphenidate partially reversed the effects of enriched housing. Implications of these results in the assessment and treatment of ADHD-related impulsivity are discussed. / Dissertation/Thesis / M.A. Psychology 2011

Previous research has indicated that musicians and bilinguals demonstrate potential cognitive benefits due to their long-term experience with music and two or more languages, respectively. For the present study, such a benefit is examined in the context of auditory inhibitory control. An auditory version of the Stroop task involving pitch and language (as used by Bialystok & DePape, 2009) was used and expanded upon. Separate groups of monolinguals, monolingual musicians, bilinguals, and tone-language bilinguals were established to investigate not only musical and bilingual experience in general, but also to determine if there is an effect of type of language on auditory inhibitory control. Additionally, a contour-based auditory Stroop task (with rising and falling tone patterns) was implemented to investigate a different dimension of auditory perception. Differences in reaction time were measured as indicators of inhibitory control. The results suggest an advantage for monolingual musicians, while a possible language effect may be detrimental to performance for bilinguals on language-based tasks. The results indicate possible shared underlying cognitive resources given the apparent transferable auditory processing benefits for musicians. The implications of these results are discussed, and future directions are proposed to address factors such as age, behavioral vs. physiological effects, and whether the performance of bilinguals is due to the nature of being bilingual, or taking the task in a non-native language.

Prepulse inhibition (PPI) is a popular paradigm in sensorimotor gating research. In healthy individuals the weak lead stimulus (i.e., the prepulse) presentation results in a reduction in the startle probe (pulse) elicited response. The motor responses to the prepulses (prepulse reactivity, PPER) were until recently largely ignored in PPI research. There are conflicting reports about prepulse reactivity and startle response modification (SRM) associations; and personality factors relevant to SRM have not been previously examined in prepulse reactivity context. Healthy participants were drawn from university student and staff population. Three paradigms were used: unpredictable stimulus onset, predictable stimulus onset and conscious stimulus processing. The stimuli consisted of 80, 85 & 90dB prepulses and 115dB startle probe separated by 140ms inter-stimulus interval (onset to onset asynchrony). The inter-trial intervals varied between the studies. Startle responses were measured as eye blinks and recorded using surface EMG. All motor responses were quantified according to the same set of rules. Prepulse-elicited motor responses reliably appeared in all the studies and were distinct from spontaneous EMG. Some PPER characteristics exhibited stimulus intensity dependence further proving PPER validity as stimulus-driven response. Prepulse reactivity exhibited significant associations with startle response modification. PPER was a stable tendency; individuals either consistently responded to the weak lead stimuli or did not. Two types of startle response modification appeared under the conditions assumed to elicit maximal inhibition only: classical inhibition (as expected) and paradoxical prepulse facilitation. These appeared in motor responses and in conscious stimulus processing. The propensity towards the paradoxical prepulse facilitation was reduced by efficient prepulse inhibition. PPER and SRM had limited associations with personality factors, sex, or age. The predictable stimulus onset paradigm however highlighted the associations of the defensive startle response and its modification with fear and anxiety. Increased emotionality, regardless of its valence, proved detrimental to sensorimotor gating.

Members of the Staphylococcus genus are a major health issue in the clinical environment and can cause a wide range of disease in humans. However, this genus is also found as a part of the normal flora in humans, usually on the skin, nasal cavities, or on the linings of the throat. Normal flora members of the Staphylococcus genus become an opportunistic infection when there is breach in the physical barriers or the immune status of the human host. Another challenge with the Staphylococcus genus is the increase in drug resistant strains, such as Methicillin resistant Staphylococcus aureus (MRSA), making simple infections difficult to treat and leading to severe toxic shock or even death. Recently, there have been numerous studies demonstrating normal flora bacterial interactions inhibiting bacteria that are potentially harmful to humans. Our research lab has previously demonstrated that the benign bacterium Alcaligenes faecalis has inhibitory effects against Staphylococcus aureus. In the present study, we wanted to explore: 1) if the inhibitory effect of A. faecalis would translate to other Staphylococcus species (S. capitis, S. saprophyticus, and S. epidermidis); 2) if this inhibitory effect was found in other Alcaligenes species (A. viscolactis). To determine this possible interactions, two parallel experimental projects were undertaken. A. faecalis and A. viscolactis were tested for their interactions with Staphylococcus species on both agar and liquid medium. For agar medium analysis, Staphylococcus lawns were grown on agar plates and either Alcaligenes cells, heat killed Alcaligenes, or Alcaligenes cell free supernatant were spotted onto the lawns and observed and scored for zones of inhibition (ZOI). It was demonstrated live cells of both A. faecalis and A. viscolactis were needed to produce ZOI on Staphylococcus lawns and that all Staphylococcus species were inhibited. For liquid medium analysis, Staphylococcus species were either inoculated alone (control) or in a co-culture with Alcaligenes, serially diluted, and colony forming units (CFU) were enumerated. Both A. faecalis and A. viscolactis inhibited all Staphylococcus species in liquid culture. Based on the results from these experiments, it is our conclusion that: 1) Alcaligenes faecalis and Alcaligenes viscolactis both possess the ability to inhibit Staphylococcus growth; 2) all Staphylococcus species are inhibited by Alcaligenes, but at varying levels. The exact mechanism of how Alcaligenes can inhibit Staphylococcus species is unknown, which will require further studies to analyze and understand the exact mechanism in order to create effective therapeutic targets to combat these increasingly resistant strains of Staphylococcus.

INTRO: There is mounting evidence to suggest a causal link between mild traumatic brain injury (mTBI) and post traumatic epilepsy (PTE). Significant ranges in the methods and definitions of “mild” TBI, each with their own limitations, make drawing cohesive conclusions from the state of the literature difficult. However, this body of work attempts to compile the literature in order to better elucidate the relationship between these populations. Ultimately, I hope this source to be a useful reference for understanding the state of the research such that one can make critical considerations in the future design of methods to definitively improve the quality of work in this field. Meaningful improvements could radically improve the outcomes for the millions of people who suffer as a result of these injuries and their lasting implications. METHODS: PubMed searches used keywords: Traumatic Brain injury (mild), Epilepsy, Concussion, Loss of cortical inhibition, Post Traumatic Epilepsy. Combinations of terms including mTBI or PTE AND MRI, fMRI, DTI, MRS, Biomarkers, TMS, EEG, and pathology. RESULTS: Strong trends persist despite the limitation in consistency of terminology and methods. Relative risk scores between 1.5 and 2.2 percent have been established across multiple long-term studies across decades of research and millions of person years, a 2-3-fold change over the baseline incidence of epilepsy in the general population (0.7%; less than one in every 100). Preclinical studies in mice have recently shown progressive increased seizure susceptibility after repeated mTBI. Within the first three weeks after injury, Glutamate homeostasis is altered meaningfully. Increased neural excitability results as the balance between excitation and inhibition shifts in the brain. An increased Glu/GABA ratio has also been linked to dysfunction in GABAergic cell populations, including parvalbumin positive inhibitory interneurons (PVI). Oxidative stress, as measured by a decreased GSH/GSSG ratio, suggests a dysregulation in homeostatic processes than can outlive clinical symptoms. Animals also display a decreased latency to induced seizure by Pentelynetetrazole (PTZ) a potent GABA receptor antagonist. Six weeks after injury, these mice have been shown to display; decreased GABA driving an increased Glu/GABA ratio, decreased EEG gamma power, and prominent signs of gliosis involving both astrocytes and microglia. Clinical investigations into the biology of this injury, utilizing a wide range of techniques, point to a loss of cortical inhibitory tone, an early hallmark of PTE. TMS findings of both reduced resting motor threshold and a shorter cortical silent period suggest a loss of cortical inhibitory tone likely shifting the excitation/inhibition balance. Signs of microstructural damage and altered cell permeability point to a disruption in chemical gradients which leads to greater functional deficits, as the parameters for normal cell function are no longer maintained. Changes in function and metabolism have been shown to outlast many of the behavioral and acute clinical symptoms suggesting a slow development but long duration of this insidious process. CONCLUSION: Mechanisms that link mTBI to PTE include a loss of cortical inhibition, increased oxidative stress and gliosis which over time increases Glu/GABA ratio, in turn increasing the likelihood of developing epilepsy. Although the relationship between mTBI and PTE has been suggested before through epidemiological studies, there is now emerging biochemical evidence to better describe this connection. Due to the high incidence of mTBI, any small increase in risk to develop PTE pursuant to concussion will affect millions of lives. With this new evidence, treatments can be designed to halt the progression and alleviate symptoms for those afflicted. The investigation of the biological mechanisms that link concussion and epilepsy is a critical step in developing treatment strategies and prophylaxis that could prove to be crucial for so many.

In an previous 72-hr mercury bioassay with the larval caddisfly Nectopsyche albida, electrophoretically detectable esterase activity was absent in exposed individuals that succumbed to mercury toxicity, while nine other enzymes remained active hours after death. Esterase activity also persisted in unexposed individuals (Benton and Guttman, 1992a.b). To test the effects of mercury exposure duration on esterase activity, additional larval N. albida were exposed under conditions identical to those in the earlier bioassay, and esterase activity in live individuals was tested electrophoretically every 12 hr. To test the effects of mercury concentration on esterase activity, unexposed N. albida larvae were electrophoresed, and the esterase-specific stain was spiked with various concentrations of mercury. Electrophoretic banding patterns were then densitometrically quantified to identity changes in esterase activity with exposure duration and mercury concentration. Results suggest that: inorganic mercury inhibited esterase activity in N. albida, inhibition increased with exposure duration, and inhibition increased with mercury concentration.

No description available.

Pavlov’s procedure for demonstrating conditioned Inhibition was applied to the case of a discriminated operant to see whether a parallel exists in the operant case. A stimulus (tone) that had become a signal for not responding when paired with one excitatory stimulus (key-color used in conjunction with a go/no-go auditory discrimination) also served as a signal for not responding when it was combined with another excitatory stimulus (key-color used for transfer test) that was clearly discriminated from the one employed in the original training. Skinner’s injections to Pavlov’s demonstration of conditioned inhibition were shown not to apply to the present experiment. A second experiment showed that training of a kind that led to a conditioned inhibitory function for a stimulus paired with nonreinforcement can also lead to a conditioned excitatory function for a stimulus paired with reinforcement. Appropriate controls made it evident that these results were not due to unconditioned effects of tone. When training and testing procedures which parallel those used in classical conditioning are applied to the discriminated operant, the functions of stimuli in the two types of conditioning prove to be more similar than was previously thought. / Thesis / Master of Arts (MA)