Alkaloid-like Molecules for Drug Discovery

The alkaloid class of natural compounds is extensively known for their variety of biological activities. A high percentage of currently employed chemotherapeutic drugs - more than 60% for cancer are of plant origin, and many are alkaloids.[1] Synthetic compounds that display similar structures to alkaloids are known as alkaloid-like molecules. Alkaloids are commonly documented to poses pharmacological properties such as antineoplasticity and acetylcholinesterase (AChE) inhibition. The Aristotelia alkaloids (1 and 2) have a broad spectrum of biological activities,[2] several of which contain the same 3-aza-bicyclo[3.3.1]nonane core structure architecture, seen in blue in Figure 2. Figure 1: Aristotelia alkaloids, 1 and 2. As these Alkaloids are both rare and require complex isolation, it is more resourceful to generate libraries of molecules with the same core scaffold through synthetic pathways, such as the Bridging Ritter reaction.[3] Through the use of the Bridging Ritter reaction with (-)-β-pinene (3) and various nitriles, a small library of alkaloid-like molecules has been synthesized. Figure 2: The bridging Ritter reaction of (-)-β-pinene with various nitriles. AChE inhibitors are currently the front line of drugs used for relieving the symptoms of Alzheimer’s disease (AD) by restoring natural levels neurotransmitter acetylcholine, found to be low in the synapse of AD suffers.[4] All of the currently approved AChE inhibitors have severe undesirable side-effects and with the diseases mortality rate expected to increase greatly, it is imperative that more suitable drug candidates be developed. Therefore, these alkaloid-like compounds were screened for AChE inhibitory activity using The TLC bioautographic method[5] and Ellman Assay[6]. A library of 27 alkaloid-like molecules has been synthesised. The library is currently undergoing in-house anticancer testing using the MTS assay[7] against the MDA-MB-231 breast cancer cell line. External screening has revealed one series of compounds to show potent inhibition properties against MCF-7 and one inparticular to be inactive against healthy mammalian (Vero cell line) and human oral cavity carcinoma (KB) respectively. Screening against AChE showed that the current library act only as weak inhibitors but combined with molecular modeling, has provided useful SAR data to guide the synthesis of more potent hits. Of significant interest is the importance the alkene functionality plays in providing activity. The recent finding of our work will be presented in details in this presentation

Overexpression, purification, and characterization of AcpK, PksG, and MmgA from Bacillus subtilis strain 168

AcpK, Sfp, PksG, and MmgA were successfully overexpressed and purified from B. subtilis 168, and a donated overexpression vector. PPT reactions with Sfp and AcpK were successfully performed. Biochemical characterization of PksG was carried out and defined by other unrelated research. MmgA was biochemically determined to be a b-keto acyl thiolase."--Abstract from author supplied metadata

Blog to be real: a mixed methods approach to defining, measuring, and determining predictors of blogger authenticity

Blogs are public sites that document the thoughts, ideas, opinions, and experiences of individuals through posts and images. Initially, these sites were reserved for political and educational discourse. However, the progression of social media and growth of virtual platforms has led to the expansion of blogs, particularly fashion and personal style blogs. Due to this shift in focus, researchers have developed a growing interest in blogs and how they are used to create and communicate online identities. With online identity development, individuals transfer aspects of the self from offline to online, a structured process that results in the creation of a digital self. Fashion bloggers use digital selves to share capital goods, such as clothing selections and accessories, as well as other appearance-related aspects of their identity, including hair and makeup. Similar to actors on stage, these performances are open to evaluation and criticism. Items that are displayed by the blogger and evaluated by an audience can validate or invalidate the online identity. In the case that the identity is invalidated, the blogger will craft and recraft the identity until approval is received from the audience. The two-fold purpose of this dissertation was to gain a better understanding of this process, specifically how fashion bloggers use appearance-related components, including capital, to construct online identities and how blog audiences assess the authenticity of these identities. To address this purpose, in-depth interviews were conducted with four fashion bloggers to understand their experiences in the blogosphere. Themes that emerged from the data were then used to develop a blogger authenticity scale. This scale was tested in Amazon Mechanical Turk (MTurk) with other related constructs, including blogger responsiveness (H1a-c) and number of sponsorships (H2a-c). Regression was used to determine the relationship between (1) blogger responsiveness and authenticity and (2) number of sponsorships and authenticity. In addition, MANOVA was used to assess gender differences on the three factors of authenticity. Findings from the in-depth interviews revealed three proposed dimensions of authenticity: (1) cognitive intimacy, (2) affirmation, and (3) transparency. These dimensions were confirmed with the completion of an exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). As it pertains to the hypotheses, blogger responsiveness had a significant positive relationship with authenticity (H1a-c supported) while number of sponsorships had a non-significant relationship with authenticity (H2a-c not supported). Lastly, males perceived stronger bonds with fashion bloggers than their female counterparts. These findings contribute to existing theory and address gaps in the literature. The new blogger authenticity scale adds a dimension to existing theory (identity theory) by addressing fashion bloggers as a relevant and important group of consumers. Moreover, the use of quantitative instruments addresses a gap in the literature by providing support to findings from previous qualitative studies. In addition, the findings have managerial implications, such as the consideration of blogger activity level when selecting brand ambassadors. Limitations include sampling techniques and suggestions for future research include examination of the perceived bond males have with bloggers

Sensory Training Effects on Obstacle Avoidance in Healthy Older Adults

The purpose of this study was to examine the effectiveness of a five-day balance training program on obstacle avoidance measures in a group of healthy older adults. A 2 × 3 repeated measures MANOVA revealed no significant differences between three groups of older adult participants. A follow-up paired t-test revealed a significant difference between the control group and the experimental and walking control groups for pre- and post-tests. These results suggest that a five-day program is ineffective for improving measures of toe clearance, heel clearance, horizontal shear, and gait velocity, but may be beneficial in delaying a loss in obstacle crossing speed in healthy older adults

Falls, Fear of Falling and an Aging Planet (Editorial)

We live on a planet where the life expectancy of many of its people has risen dramatically since the mid-20th Century. A baby born in Japan in 1900 was expected to live only to age 50; now, the average age is 83 years (National Institute on Aging, 2011). As a result, the number of people over age 65 has exploded. In 2008, it was estimated at 506 million; by 2040, it will exceed 1 billion. And, as our longevity increases, the number of individuals in the ‘oldest old’ group (85 years+) increases dramatically. Globally, the size of this group is expected to increase by 350% by 2050; the number of individuals over 100 will increase by 1000%

Historic tax incentives as disaster relief: a case study on post-Katrina New Orleans

Federal historic preservation tax incentives for rehabilitation projects are one of the most successful preservation tools used to reinvest in and rebuild blighted neighborhoods. In this thesis, I studied how Federal historic tax credits were used to rebuild historic architecture following a natural catastrophe. By uncovering trends among project rehabilitation descriptions, project totals, and project locations throughout New Orleans, I show that preservation tax credits were successfully used as a preservation tool in overall disaster relief efforts. The information collected and developed in this thesis has the ability to inform state and national officials responsible for promoting Federal tax incentives about the nature of these projects following a catastrophic event. In post-Katrina New Orleans, the destruction of historic housing was widespread with approximately 70% of housing units damaged in the storm. In this study, I looked at all rental-residential rehabilitation projects that utilized the tax credits between 2002 and 2009 to better understand the effectiveness of the tax credits following a natural disaster. For my research, I employed visual analysis, quantitative data analysis, and interpretive mapping techniques. Through visual analysis I assessed property conditions prior to and following rehabilitation. Quantitative data was used to compare the total number of projects, the total amount of certified investments, and approximate certification time. This information was used to compare data throughout the eight years of study to identify any similarities, differences, or trends apparent prior to and following Katrina. Mapping techniques described specific locations of projects throughout the city and the state while comparing project locations prior to and following Hurricane Katrina. This technique identified any project location shifts to more flood-damaged areas following the storm

Force and Accuracy Throws by Older Adults: II

Older adults were tested to clarify findings of an earlier examination of movement responses to shifting task requirements (Williams et al., 1993). Eleven participants (average age = 77 years) were evaluated on form and velocity as they performed overarm throws for force and accuracy. Significant gender and force-accuracy differences occurred for resultant velocity. Although no statistically significant differences occurred for force-accuracy comparisons of movement form, there were trends toward change in most movement components. Additionally, many individuals displayed change in one or more components as they shifted from force to accuracy throws. Results of this study point to the importance of examining developmental status and task requirements simultaneously

The Temporal Structure of the Forward Roll: Inter- and Intra-Limb Coordination

Investigations of the temporal structure of actions like walking, running, and hopping have given us information about movement's underlying structure. 'Rules' governing the timing of these cyclic, repetitive skills might be similar to those found for other actions. The forward roll was selected for study because there had been some previous investigation of the course of its development (Williams 1980). Children, aged 5, 7, and 9 years participated in this study. Analysis of the absolute and relative timing of selected actions revealed no statistical differences. A subset of these data was digitized to permit a deeper analysis of the rolling action. Correlation coefficients examining inter- and intra-limb timing relationships suggested the presence of tight coupling between segments in young children. Linkages were found between hip and leg segments as well as between hand contact and leg action. Magnitudes of correlations fell across the ages tested. This pattern of differences suggested that young children constrained their body segments more tightly than older subjects, to offset control problems like balance. Older subjects were more willing, or able to remain off balance for longer periods, in order to build greater speed during performance

Development of the Concept of Middleness in Children: Response Time and Complexity

24 boys and 16 girls ages 4 through 7 years were tested on an apparatus that required children to select the middle of 3, 5, 7, or 9 stimulus lights when arranged adjacent to one another and when spaced symmetrically or asymmetrically. Analysis indicated response time decreased with age and increased as a function of the number of stimulus lights in the task. Time to respond to asymmetrical arrangements was greater than for problems whose stimuli were arranged symmetrically

Age, Gender, and Flexibility Differences in Tennis Sewing Among Experienced Older Adults

This study examined tennis serving in older adult tennis players. Twentytwo older adults, divided into younger and older halves, were videotaped serving five "first" serves. Dominant shoulder flexibility also was measured. From the videotape, servers were classified into developmental levels and their resultant ball impact velocity was calculated. An Age x Gender (2 x 2) mixed model MANOVA yielded no significant differences between the age groups or between men and women in flexibility, ball impact velocity, or movement pattern. A few combinations of the developmental levels of elbow and forearmlracket action were used by the majority of servers. Regular practice might consolidate older adults in these attractor movement patterns, making them more resilient to change than with less practiced skills. These results suggest practice in older adulthood favorably affects performance by resulting in consistency of movement pattern and maintenance of movement pattern, flexibility, and ball impact speed