Maternal Behavior is Impaired in Female Mice Lacking Type 3 Adenylyl Cyclase

Although chemosensory signals generated by mouse pups may trigger maternal behavior of females, the mechanism for detection of these signals has not been fully defined. As some odorant receptors are coupled to the type 3 adenylyl cyclase (AC3), we evaluated the role of AC3 for maternal behavior using AC3−/− female mice. Here, we report that maternal behavior is impaired in virgin and postpartum AC3−/− mice. Female AC3−/− mice failed the pup retrieval assay, did not construct well-defined nests, and did not exhibit maternal aggression. Furthermore, AC3−/− females could not detect odorants or pup urine in the odorant habituation test and were unable to detect pups by chemoreception. In contrast to wild-type mice, AC activity in main olfactory epithelium (MOE) preparations from AC3−/− female mice was not stimulated by odorants or pheromones. Moreover, odorants and pheromones did not evoke electro-olfactogram (EOG) responses in the MOE of AC3−/− female mice. We hypothesize that the detection of chemical signals that trigger maternal behavior in female mice depends upon AC3 in the MOE

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing pathophysiological changes in the brain associated with HAND. Aberrantly expressed transcripts common to untreated and treated HAND may contribute to neurocognitive changes defying ART

Absolute spin calibration of an electron spin polarimenter by spin-resolved photoemission from the Au(111) surface states

Here we report the absolute characterization of a spin polarimeter by measuring the Sherman function with high precision. These results have been obtained from the analysis of the spin and angle-resolved photoemission spectra of Au(111) surface states. The measurements have been performed with a 250 kHz repetition rate Ti:sapphire amplified laser system combined with a high energy-, angle-, and spin-resolving time-of-flight electron spectrometer

Organizational Controls, Social Ties and Performance in Plural Sourcing

This is the author accepted manuscript. The final version is available from Springer International Publishing via the DOI in this record.This paper seeks to shed light on the effect of organizational controls and social ties on sourcing performance in a plural sourcing setting. In plural sourcing, the controller makes organizational control choices for both internal and external sourcing providers. The plural sourcing context offers the controller the benefit of insight into the effectiveness of organizational controls in each sourcing mode (i.e., external and internal), thus allowing the controller to both mitigate risk and also attempt to enhance performance where risk is not present. We therefore posited that a plural sourcing controller has three strategies to improve performance when considering the use of organizational controls. First, a controller may follow a risk-mitigation strategy against specific hazards to defuse supplier opportunistic behavior, coined here as risk-mitigating controls. Secondly, the controller may use organizational controls that enhance performance (i.e., performance-enhancing controls), while not necessarily mitigating risk. Last but not least, the controller may improve relationships with controllees in order to improve the effectiveness of organizational controls. Based on the results of a survey of senior managers involved in plural sourcing in 122 large firms in the UK and USA, we find support for the use of both risk-mitigating and performance-enhancing controls in the internal provider setting, but no support for similar strategies in the external provider setting. Instead, stronger social ties demonstrate a greater moderating effect in the external provider compared to the internal provider setting