Transdermal and Oral dl-Methylphenidate-Ethanol Interactions in C57BL/6J Mice

The persistence of attention-deficit/hyperactivity disorder (ADHO) into adulthood has been increasingly recognized over the past few decades and the stimulant drug dl-methylphenidate (MPH) has remained a first-line pharmacotherapeutic agent in the treatment of ADHD. Many adult ADHD patients who are prescribed MPH report concomitant use with ethanol. In humans, coadministration of dl-MPH and ethanol results in pharmacokinetic and pharmacodynamic drug - drug interactions. Ethanol elevates biological concentrations of the pharmacologically active d-MPH isomer and yields the metabolic transesterification product ethylphenidate (EPH). EPH appears to be formed through the actions of carboxylesterase 1 (CES1) which exhibits I-MPH substrate enantioselectivity in both the metabolic transesterification and deesterification pathways. Accordingly, the mean absolute oral bioavailability of I-MPH is limited to only 1-3% compared to approximately 30% for d-MPH. However, dosing with transdermal dl-MPH (Daytrana® avoids the extensive oral presystemic metabolism and leads to approximately 50 times more I-MPH reaching the systemic circulation when compared with oral dosing. Studies using human subjects are limited in their ability to examine abuse like doses. Using a C57BL/6J mouse model, the experiments in this dissertation were designed to: 1) Establish the rewarding properties and abuse potential of Lv. dl-MPH as evidenced by drug seeking behavior; 2) Investigate the pharmacokinetic interactions of dl-MPH and ethanol coabuse, placing an emphasis on the MPH transdermal system; 3) Investigate the pharmacodynamic interactions of dl-MPH and ethanol coabuse. The reward value of methylphenidate is evidenced by robust drug-seeking behavior in C57 mice, which are an appropriate model to investigate methylphenidate abuse liability. Pharmacokinetic studies showed that, as in humans, transdermal dl-MPH greatly facilitated the absorption of I-MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of I-EPH and to an elevation in d-MPH concentrations with both transdermal and oral dl-MPH. While only guarded comparisons between transdermal and oral dl-MPH can be made due to route-dependent drug absorption rate differences, transdermal dl-MPH was associated with significant MPH - ethanol interactions. Pharmacodynamic studies showed that an otherwise depressive dose of ethanol significantly potentiated oral dl-MPH induced increases in total distance traveled for the first 100 min. Further, transdermal dl-MPH increased total distance traveled after a latency of 80 min, though this effect was not potentiated by concomitant ethanol. The results from these studies in combination with human data, provide a scientific basis for extending abuse precautions for the ethanol - dl-MPH combination in general, with a novel focus on transdermal dl-MPH

An Exploration of Bedtime Music Genres and Sleep Quality

Various studies have been conducted to research beneficial sleep practices including audio, such as music or white noise. Younger individuals have access to phones and unique sleep aids that claim to benefit one’s sleep quality. It’s a common enough practice to turn on music to alleviate the mind, guiding it towards relaxation. Surprisingly, there is a lack of consensus on the helpfulness of music, with some studies finding it harms rather than aids. Seeing as sleep is a crucial factor of healthy living, it’s a worthwhile pursuit to discover whether music can improve sleep quality and duration. Our study aimed to investigate the relation between one’s overall sleep quality and the integration of music prior to bedtime. Participants were recruited through Belmont University’s Psychology department, and individuals were compensated by gaining class credit for introductory Psychology courses. Prior to bedtime, the first half of participants were required to listen to three non-lyrical songs (chosen by researchers), and the second half listened to three lyrical songs. The following morning, participants were asked to complete a Qualtrics survey questionnaire. The second night and morning consisted of the same process, simply listening to the other type of songs prior to sleep. After observing participant’s sleep quality after listening to lyrical or non-lyrical music, researchers will analyze the and determine which music type is more beneficial for sleep. Results are projected to reveal that listening to non-lyrical music prior to bedtime is more beneficial for sleep quality because it is found to be more soothing and less distracting when falling asleep

FACTOR ANALYSIS OF INTERN EFFECTIVENESS

Four factors in teaching intern effectiveness, as measured by a Praxis III-similar instrument, were found among observational data of teaching interns during the 2010 spring semester. Those factors were lesson planning, teacher/student reflection, fairness & safe environment, and professionalism/efficacy. This factor analysis was as much of a statement about effective teaching as it is about the technical aspects of an instrument utilized to assess it. Forty-one percent of effective teaching was found to be in the lesson planning

Two objects or one? similarity rather than complexity determines objecthood when resolving dynamic input

The human brain is continuously confronted with dynamic visual input, and from this it must infer whether input belongs to a single versus multiple object identities across time. Object substitution masking (OSM), in which perception of a target stimulus is impaired by a temporally trailing 4-dot mask, reflects a failure to segment the target and mask as discrete objects. According to Bouvier and Treisman (2010), OSM only occurs for targets that require binding multiple separate features (e.g., color and orientation) to be identified. In contrast, a target that represents a unique feature is thought to be impervious to masking. Here, however, we show that a single orientation target (a Gabor) is susceptible to masking with an orientation-discrimination task, but only when the mask is similar in orientation to the target. That is, target-mask similarity, rather than target complexity determines masking. A reexamination of Bouvier and Treisman’s (2010) results show that they can be explained within this target-mask similarity perspective. This means that the similarity of 2 objects determines whether they will be integrated or segmented across time, rather than the complexity of 1 of the objects in isolation.The research was supported by an Australian Research Council grant: arc ID:de140101734

In Vivo Biotinylation of the Toxoplasma Parasitophorous Vacuole Reveals Novel Dense Granule Proteins Important for Parasite Growth and Pathogenesis.

UnlabelledToxoplasma gondii is an obligate intracellular parasite that invades host cells and replicates within a unique parasitophorous vacuole. To maintain this intracellular niche, the parasite secretes an array of dense granule proteins (GRAs) into the nascent parasitophorous vacuole. These GRAs are believed to play key roles in vacuolar remodeling, nutrient uptake, and immune evasion while the parasite is replicating within the host cell. Despite the central role of GRAs in the Toxoplasma life cycle, only a subset of these proteins have been identified, and many of their roles have not been fully elucidated. In this report, we utilize the promiscuous biotin ligase BirA* to biotinylate GRA proteins secreted into the vacuole and then identify those proteins by affinity purification and mass spectrometry. Using GRA-BirA* fusion proteins as bait, we have identified a large number of known and candidate GRAs and verified localization of 13 novel GRA proteins by endogenous gene tagging. We proceeded to functionally characterize three related GRAs from this group (GRA38, GRA39, and GRA40) by gene knockout. While Δgra38 and Δgra40 parasites showed no altered phenotype, disruption of GRA39 results in slow-growing parasites that contain striking lipid deposits in the parasitophorous vacuole, suggesting a role in lipid regulation that is important for parasite growth. In addition, parasites lacking GRA39 showed dramatically reduced virulence and a lower tissue cyst burden in vivo Together, the findings from this work reveal a partial vacuolar proteome of T. gondii and identify a novel GRA that plays a key role in parasite replication and pathogenesis.ImportanceMost intracellular pathogens reside inside a membrane-bound vacuole within their host cell that is extensively modified by the pathogen to optimize intracellular growth and avoid host defenses. In Toxoplasma, this vacuole is modified by a host of secretory GRA proteins, many of which remain unidentified. Here we demonstrate that in vivo biotinylation of proximal and interacting proteins using the promiscuous biotin ligase BirA* is a powerful approach to rapidly identify vacuolar GRA proteins. We further demonstrate that one factor identified by this approach, GRA39, plays an important role in the ability of the parasite to replicate within its host cell and cause disease

Watching plants grow:A position paper on computer vision and Arabidopsis thaliana

The authors present a comprehensive overview of image processing and analysis work done to support research into the model flowering plant Arabidopsis thaliana. Beside the plant's importance in biological research, using image analysis to obtain experimental measurements of it is an interesting vision problem in its own right, involving the segmentation and analysis of sequences of images of objects whose shape varies between individual specimens and also changes over time. While useful measurements can be obtained by segmenting a whole plant from the background, they suggest that the increased range and precision of measurements made available by leaf‐level segmentation makes this a problem well worth solving. A variety of approaches have been tried by biologists as well as computer vision researchers. This is an interdisciplinary area and the computer vision community has an important contribution to make. They suggest that there is a need for publicly available datasets with ground truth annotations to enable the evaluation of new approaches and to support the building of training data for modern data‐driven computer vision approaches, which are those most likely to result in the kind of fully automated systems that will be of use to biologists

The anomalous process gamma pi -> pi pi to two loops

The amplitude for the anomalous process gamma pi -> pi pi is evaluated to two loops in the chiral expansion by means of a dispersive method. The two new coupling constants that enter at this order are estimated via sum rules derived from a non-perturbative chiral approach. With these coupling constants fixed, the numerical results are given and compared with the available experimental information.Comment: 23 pages, 4 figure