Genipin-Induced Inhibition of Uncoupling Protein-2 Sensitizes Drug-Resistant Cancer Cells to Cytotoxic Agents

Uncoupling protein-2 (UCP2) is known to suppress mitochondrial reactive oxygen species (ROS) production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents

Leadership Training for Transforming the Community: A Participatory Approach

The study described here examined the effects of the leadership training workshops on selected residents in Clayton, a rural Alabama city. Data were obtained from 40 participants by a survey questionnaire administered 6 months after the workshops. The results showed that the workshops were well received and that many participants are using the information gained for community development. The participatory approach to training has sound philosophical and practical implications for effective community development. When participants are involved in identifying their needs and are included in planning of the training process, they are more likely to receive and use information provided

Intensity-based image registration using multiple distributed agents

Image registration is the process of geometrically aligning images taken from different sensors, viewpoints or instances in time. It plays a key role in the detection of defects or anomalies for automated visual inspection. A multiagent distributed blackboard system has been developed for intensity-based image registration. The images are divided into segments and allocated to agents on separate processors, allowing parallel computation of a similarity metric that measures the degree of likeness between reference and sensed images after the application of a transform. The need for a dedicated control module is removed by coordination of agents via the blackboard. Tests show that additional agents increase speed, provided the communication capacity of the blackboard is not saturated. The success of the approach in achieving registration, despite significant misalignment of the original images, is demonstrated in the detection of manufacturing defects on screen-printed plastic bottles and printed circuit boards

Impact of Socioeconomic Factors on Florida Consumers\u27 Perceptions on Use of Chemical in Locally or Regionally Produced Livestock Products

Abstract The use of chemicals in livestock production has been an issue for consumers for several decades. This study, therefore, assessed the impact of socioeconomic factors on Florida consumers’ perceptions on the use of chemicals in locally or regionally produced livestock products. Data were collected from a sample of 404 participants from several Florida counties and were analyzed using descriptive statistics and ordinal logistic analysis. Most of the respondents were of the opinion that using chemicals in locally or regionally produced and sold beef or goat meat was a serious or somewhat serious hazard. The ordinal logistic regression results showed that several socioeconomic factors, such as household size, gender, age, and education had significant effects on pesticide residues; antibiotics; artificial fertilizers; additives and preservatives, and artificial coloring. It was recommended that producers and processors should minimize the use of chemicals in livestock products as this has both short- and long-term benefits. Keywords: Socioeconomic Factors, Chemicals, Consumer Perceptions, Locally or Regionally Produced, Livestock Product

Advances in studying phasic dopamine signaling in brain reward mechanisms

The last sixty years of research has provided extraordinary advances of our knowledge of the reward system. Since its discovery as a neurotransmitter by Carlsson and colleagues (1), dopamine (DA) has emerged as an important mediator of reward processing. As a result, a number of electrochemical techniques have been developed to measure DA in the brain. Together, these techniques have begun to elucidate the complex roles of tonic and phasic DA signaling in reward processing and addiction. In this review, we will first provide a guide for the most commonly used electrochemical methods for DA detection and describe their utility in furthering our knowledge about DA's role in reward and addiction. Second, we will review the value of common in vitro and in vivo preparations and describe their ability to address different types of questions. Last, we will review recent data that has provided new mechanistic insight of in vivo phasic DA signaling and its role in reward processing and reward-mediated behavior

Differential role of ventral tegmental area acetylcholine and N-methyl-D-aspartate receptors in cocaine-seeking

Exposure to drug-associated cues evokes drug-seeking behavior and is regarded as a major cause of relapse. Cues evoke burst firing of ventral tegmental area (VTA) dopamine (DA) neurons and phasic DA release in the nucleus accumbens (NAc). Cholinergic and glutamatergic input to the VTA is suggested to gate phasic DA activity. However, the role of VTA cholinergic and glutamatergic receptors in regulating phasic dopamine release and cue-induced drug-seeking in cocaine experienced subjects is not known. In male Sprague-Dawley rats, we found that VTA inactivation strongly inhibited, while VTA stimulation promoted, cocaine-seeking behavior during early withdrawal. Blockade of phasic activated D1 receptors in the NAc core also strongly inhibited cue-induced cocaine-seeking--suggesting an important role of phasic DA activity in the VTA to NAc core circuit. Next, we examined the role of VTA acetylcholine receptors (AChRs) and N-methyl-D-aspartate receptors (NMDARs) in regulating both NAc core phasic DA release and cue-induced cocaine-seeking. In cocaine naïve subjects, VTA infusion of the nicotinic acetylcholine receptor (AChR) antagonist mecamylamine, the muscarinic AChR antagonist scopolamine, or the NMDAR antagonist AP-5, led to robust attenuation of phasic DA release in the NAc core. During early cocaine withdrawal, VTA infusion of AP-5 had limited effects on NAc phasic DA release and cue-induced cocaine-seeking while VTA infusion of mecamylamine or scopolamine robustly inhibited both phasic DA release and cocaine-seeking. The results demonstrate that VTA AChRs, but not NMDARs, strongly regulate cue-induced cocaine-seeking and phasic DA release during early cocaine withdrawal

An Analysis of the Characteristics and Practices of Selected Florida Small Livestock Producers: A Focus on Economics and Marketing

Issues regarding economics and marketing are of importance to small livestock producers, who produce and sell locally or regionally. This study, thus, assessed the characteristics and practices of selected Florida small livestock producers, emphasizing economics and marketing. Data were collected from a convenience sample of seventy small producers from several Florida counties, and were analyzed using descriptive statistics, including chi-square tests. The findings showed that there were many more: full-time producers; producers with at least a two-year/technical degree, and producers with at, least, a $40,000 annual household income. Most had been farming more than fifteen years, on at least 50 acres, and had small herds. Furthermore, very few of them made profits; they mainly sold animals live on-farm or at the auction/stockyard, and many of them kept records. Chi-square tests showed that gender, age, education, and household income had statistically significant effects on selected marketing characteristics. The findings suggest that educational programs that emphasize economic and marketing issues should be taken into consideration when designing programs for small producers in the study area. Keywords: Livestock Producers, Small Producers, Characteristics and Practices, Economics and Marketin

An Analysis of Earned Income Tax Credit Filers and Earned Income Tax Credit Non-Filers in Rural Communities

This study focuses on assessing differences between earned income tax credit (EITC) filers and non-filers, specifically, identifying general characteristics, examining willingness to participate in asset building programs, and identifying key factors affecting EITC filing status. The data were obtained from a convenience sample of respondents in South Central Alabama, and were analyzed using descriptive statistics. The results showed that many respondents did not know that the EITC could be used as an asset-building tool. Also, the results revealed that socioeconomic characteristics played a role in whether or not one filed for the EITC. Since many respondents did not know that the EITC could be used as an asset-building strategy, it is recommended that financial education programs be created to encourage respondents to adopt the EITC as an asset-building tool. In addition, it is recommended that socioeconomic characteristics be taken into account when dealing with EITC policy

Perception and risk factors for cervical cancer among women in northern Ghana

Objective: This study assessed the perception of risk of cervical cancer and existence of risk factors for cervical cancer based on five known risk factors among women attending the Tamale Teaching Hospital in Tamale, Ghana.Methods: A consecutive sample of 300 women was interviewed using a semi structured questionnaire to inquire about risk factors and perception of risk of cervical cancer. Specific risk factors that were explored included early coitarche, multiple sexual partners, polygamous relationships, history of smoking, and having a current partner who had multiple sexual partners.Results: Sixty-one per cent of women reported that they had no personal risk for cervical cancer. 27% of respondents were in polygamous relationships, and of those, more than half didn’t think they were at an increased risk of cervical cancer. 2 women had a total of ≥ 5 sexual partners in their lifetime and neither believed they were at any risk for cervical cancer. 23% said their current partner had had at least 2 sexual partners in his lifetime, and of those, (61%) thought they were at no risk for cervical cancer. 46% of respondents reported not having any of the risk factors listed in the study. 23% of respondents reported having one risk factor while 21% had two risk factors and 11% had three or more risk factors.Conclusion: Women’s perception of personal risk for cervical cancer is lower than their actual risk based on the five behavioural risk factors assessed and a lack of knowledge of the personal factors for the diseaseFunding: This project was supported by NIH Research Training Grant #R25 TW009345 funded by the Fogarty International Centre, in partnership with several NIH Institutes (NIMH, NIGMS, NHLBI, OAR and OWH)Keywords: Cervical Cancer, Risk, Perceptions, Northern Ghan

The Impact of Socioeconomic Factors on Selected Practices by Small Livestock Producers in Florida

Socioeconomic factors could affect the practices of small livestock producers who produce and sell locally or regionally. Yet, there is limited research on the issue in the Southeastern U.S., for example, Florida. Thus, this study assessed the impact of socioeconomic factors on practices of small livestock producers in Florida. The data were obtained from a sample of seventy producers from several counties in Florida, and were analyzed using descriptive statistics and logistic regression analysis. The results showed that a majority practiced rotational grazing; did not test soil regularly; had parasite problems; did not use veterinary services, and practiced record keeping. Further, the binary logistic regression analyses showed that selected socioeconomic factors had statistically significant effects on selected practices. For instance, gender had a statistically significant effect on soil testing; household income had a statistically significant effect on parasite problem; gender had a statistically significant effect on the use of veterinary services; and farming status, race/ethnicity, education, and household income had statistically significant effects on record keeping. The findings suggest that socioeconomic factors may be important in producers adopting practices. Keywords: Socioeconomic Factors, Selected Practices, Farm Practices, Small Livestock Producers, Small Producer