Antiproliferative Role of Dopamine: Loss of D2 Receptors Causes Hormonal Dysfunction and Pituitary Hyperplasia

AbstractThe function of dopamine (DA) in the nervous system is paralleled by its neuroendocrine control of pituitary gland functions. Here, we document the neuroendocrine function of dopamine by studying the pituitary gland of mice lacking DA D2 receptors (D2R). These mice present a striking, progressive increase in lactotroph number, which ultimately leads to tumors in aged animals. Females develop tumors much earlier than males. An estrogen-mediated lactotroph proliferation cannot account for this sexual dimorphism, since D2R-null females are hypoestrogenic and, thus, have estrogen levels similar to males. In contrast, prolactin levels are six times higher in females than in males. We show that active prolactin receptors are present in the pituitary and their expression increases in concomitance with tumor expansion. These results point to prolactin as an autocrine proliferative factor in the pituitary gland. Additionally, they demonstrate an antiproliferative function for DA regulated through D2 receptor activation

Best-shot versus weakest-link in political lobbying: an application of group all-pay auction

We analyze a group political lobbying all-pay auction with a group specific public good prize, in which one group follows a weakest-link and the other group follows a best-shot impact function. We completely characterize all semi-symmetric equilibria. There are two types of equilibria: (1) each player in the best-shot group puts mass at the upper bound of the support, whereas each player in the other group puts mass at the lower bound of the support; (2) players in the best-shot group put masses at both the lower and the upper bounds, while the other group randomizes without a mass point. An earlier and longer version of this study was circulated under the title “The Group All-pay Auction with Heterogeneous Impact Functions.” We appreciate the comments of an Associate Editor and two anonymous referees, Kyung Hwan Baik, Walter Enders, Matt Van Essen, Paan Jindapon, David Malueg, Paul Pecorino, Seth Streitmatter, Ted Turocy, the participants at the 2015 conference of ‘Contest: Theory and Evidence’ at the University of East Anglia, and the seminar participants at the University of Alabama and Korea University. Iryna Topolyan gratefully acknowledges the support from the Charles Phelps Taft Research Center. Any remaining errors are our own

Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast

<p>Abstract</p> <p>Background</p> <p>Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer.</p> <p>Methods</p> <p>DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction.</p> <p>Results</p> <p>Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001).</p> <p>Conclusion</p> <p>Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.</p

Identification of Domains Directing Specificity of Coupling to G-proteins for the Melanocortin MC3 and MC4 Receptors

The melanocortin receptors, MC3R and MC4R, are G protein-coupled receptors that are involved in regulating energy homeostasis. Using a luciferase reporter gene under the transcriptional control of a cAMP-responsive element (CRE), the coupling efficiency of the MC4R and MC3R to G-proteins was previously shown to be different. MC4R exhibited only 30-50% of the maximum activity induced by MC3R. To assess the role of the different MC3R and MC4R domains in G-protein coupling, several chimeric MC3R/MC4R receptors were constructed. The relative luciferase activities, which were assessed after transfecting the chimeric receptors into HEK 293T cells, showed that the i3 (3rd intracellular) loop domain has an essential role in the differential signaling of MC3R and MC4R. To reveal which amino acid residue was involved in the MC4R-specific signaling in the i3 loop, a series of mutant MC4Rs was constructed. Reporter gene analysis showed that single mutations of Arg220 to Ala and Thr232 to either Val or Ala increased the relative luciferase activities, which suggests that these specific amino acids, Arg220 and Thr232, in the i3 loop of MC4R play crucial roles in G-protein coupling and the subtype-specific signaling pathways. An examination of the inositol phosphate (IP) levels in the cells transfected with either MC3R or MC4R after being exposed to the melanocortin peptides revealed significant stimulation of IP production by MC3R but no detectable increase in IP production was observed by MC4R. Furthermore, none of the MC4R mutants displayed melanocortin peptide-stimulated IP production. Overall, this study demonstrated that MC3R and MC4R have distinct signaling in either the cAMP- or the inositol phospholipid-mediated pathway with different conformational requirements

High birth weight as an important risk factor for infant leukemia

In this paper, we compared the birth weight distribution among 201 infant leukaemia (IL) cases with that of 440 noncancer controls enrolled in Brazil in 1999–2005. Compared with the general population and the stratum 2500–2999 g as reference, IL cases weighing 3000–3999 g presented an odds ratio (OR) of 1.68 (95% CI: 1.03–2.76), and those of 4000 g or more, an OR of 2.28 (95% CI: 1.08–4.75), Ptrend<0.01. Using hospital-based controls, the OR for 4000 g or more, compared to 2500–2999 g, was 1.30 (95% CI: 1.02–1.43) after adjusting for confounders (gender, income, maternal age, pesticide and hormonal exposure during pregnancy). The results suggest that high birth weight is associated with increased risk of IL

The interaction of ultrasound with a partially contacting solid-solid interface in the low frequency regime

When real engineering surfaces touch, contact occurs between the asperities of the surface roughness. For this reason the true area of contact between components can be significantly less than the apparent contact area and the stresses at the asperities are considerably higher than the average (nominal) contact pressure. Measurement of the degree of contact between solids is important in a number of applications such as the design of contacting elements (e.g. gears and bearings) [1] and the detection of ‘kissing’ bonds [2]

Bedside Sublingual Video Imaging of Microcirculation in Assessing Bacterial Infection in Cirrhosis

Bacterial infections are common in cirrhosis and can lead to life-threatening complications. Sidestream dark-field (SDF) imaging has recently emerged as a noninvasive tool for capturing real-time video images of sublingual microcirculation in critically ill patients with sepsis. The objective of this study was to assess the utility of SDF in determining underlying infection in patients with cirrhosis. Sublingual microcirculation was compared among patients with compensated cirrhosis (Group A, n = 13), cirrhosis without sepsis (Group B, n = 18), cirrhosis with sepsis (Group C, n = 14), and sepsis only (Group D, n = 10). The blood flow was semi-quantitatively evaluated in four equal quadrants in small (10–25 mm); medium (26–50 mm); and large (51–100 mm) sublingual capillaries. The blood flow was described as no flow (0), intermittent flow (1), sluggish flow (2), and continuous flow (3). The overall flow score or microvascular flow index (MFI) was measured for quantitative assessment of microcirculation and predicting power for concurrent infection in cirrhosis. Marked impairment was observed at all levels of microvasculature in Groups B and C when compared with Group A. This effect was restricted to small vessels only when Group B was compared with Group C. MFI < 1.5 was found to have highest sensitivity (100%) and specificity (100%) for infection in decompensated cirrhosis. SDF imaging of sublingual microcirculation can be a useful bedside diagnostic tool to assess bacterial infection in cirrhosis

The Revised Edition of Korean Calendar for Allergenic Pollens

The old calendar of pollens did not reflect current pollen distribution and concentrations that can be influenced by changes of weather and environment of each region in South Korea. A new pollen calendar of allergenic pollens was made based on the data on pollen concentrations obtained in eight regions nationwide between 1997 and 2009. The distribution of pollen was assessed every day at 8 areas (Seoul, Guri, Busan, Daegu, Jeonju, Kwangju, Kangneung, and Jeju) for 12 years between July 1, 1997 and June 30, 2009. Pollens were collected by using Burkard 7-day sampler (Burkard Manufacturing Co Ltd, UK). Pollens which were stained with Calberla's fuchsin staining solution were identified and counted. Pine became the highest pollen in May, and the pollen concentrations of oak and birch also became high. Ragweed appeared in the middle of August and showed the highest pollen concentration in the middles of September. Japanese hop showed a high concentration between the middle of August and the end of September, and mugwort appeared in the middles of August and its concentration increased up until early September. In Kangneung, birch appeared earlier, pine showed a higher pollen concentration than in the other areas. In Daegu, Oriental thuja and alder produced a large concentration of pollens. Pine produced a large concentration of pollens between the middle of April and the end of May. Weeds showed higher concentrations in September and mugwort appeared earlier than ragweed. In Busan the time of flowering is relatively early, and alder and Oriental thuja appeared earliest among all areas. In Kwangju, Oriental thuja and hazelnut appeared in early February. Japanese cedar showed the highest pollen concentration in March in Jeju. In conclusion, update information on pollen calendar in South Korea should be provided for allergic patients through the website to manage and prevent the pollinosis