The Neuroprotective Effect Of Decreased Luteinizing Hormone On Astrocytic Pathology In An Alzheimer\u27s Disease Model

After menopause or ovariectomy (ovx) females have high levels of luteinizing hormone (LH) which may contribute to and exacerbate Alzheimer’s disease (AD). High levels of LH have been associated with decreased spatial memory and increased amyloid-beta levels, both characteristic of Alzheimer’s disease. Conversely, by decreasing levels of this hormone, studies have been able to improve the memory of normal, nonAD rats and recover memory deficits in animal models of AD. Based on this research, it was hypothesized that female rats with low, as compared to high, levels of LH would show less hippocampal damage in an animal model of AD. To create an Alzheimer’s disease model, the neurotoxins amyloid-beta and ibotenic acid were infused into the hippocampus of female Sprague-Dawley rats. To vary LH levels, rats were either ovx so they had high LH levels or were ovx and given Antide, a GnRH antagonist that decreases LH levels. Antide or vehicle were administered either 1d before (early Antide) or beginning 4d after (late Antide) the neurotoxin infusion. This resulted in 4 groups of ovx females: Control, AD, AD + early Antide, and AD + late Antide. Damage was ascertained using immunocytochemistry for glial fibrillary acidic protein (GFAP), an intermediate filament protein specific to astrocytes of the central nervous system. Astrocytic pathology within the CA1 region of the hippocampus was determined by the number of GFAP immunoreactive cells, astrocyte cell size, and GFAP content (area covered by stained pixels). Ovx AD females had an increased number of GFAP-containing cells, increased astrocytic cell size, and increased GFAP content compared to ovx control animals. Early Antide treatment prior to neurotoxin infusion resulted in a decreased cell number and a decreased GFAP content compared to the AD group. Furthermore, while AD+late Antide treatment had no effect on cell number compared to the AD females, it did result in decreased GFAP content. Lastly, cell size for both Antide treatment groups was intermediate between the AD and control groups. These results provide evidence that low levels of LH results in decreased neural damage in CA1 in an AD model. This suggests that high levels of LH such as those seen after menopause are harmful to the hippocampus and may contribute to the damage seen during AD, and that an LH antagonist could play either a preventative and/or therapeutic role in the treatment of Alzheimer’s disease

The androgen receptor governs the execution, but not programming, of male sexual and territorial behaviors

Testosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior remains to be established. Circulating testosterone activates the androgen receptor (AR) and also serves as the source of estrogen in the brain. We have used a genetic strategy to delete AR specifically in the mouse nervous system. This approach permits us to determine the function of AR in sexually dimorphic behaviors in males while maintaining circulating testosterone levels within the normal range. We find that AR mutant males exhibit masculine sexual and territorial displays, but they have striking deficits in specific components of these behaviors. Taken together with the surprisingly limited expression of AR in the developing brain, our findings indicate that testosterone acts as a precursor to estrogen to masculinize the brain and behavior, and signals via AR to control the levels of male behavioral displays

Entrepreneurship in Peace Operations

Journal of Civic Society," 6(01), (2010), pp. 1-21.A central question guides this article: To what extent can entrepreneurship be a force for change and transformation in war-torn areas? To address the question, this article introduces the topic of social entrepreneurship and illustrates how social entrepreneurs are serving as change agents in rebuilding and reconstructing areas devastated by conflict. The social enterprise of Kiva, the brainchild of social entrepreneurs Matthew Flannery and Jessica Jackley, provides an example. It is notable for its innovative idea—a Web-based, internet-facilitated micro-loan process that attracts individual investors worldwide in support of business entrepreneurs in the developing world. As a counter example to top-down, mandate-driven, organization-centric intervention strategies that many organizations pursue in peace operations, Kiva’s enduring legacy may very well be its bottom-up, entrepreneur-driven, network-centric model of change. Its most salient features are: a supply chain that ‘contractually’ connects all the partners in the loan process to minimize coordination problems and ensure that each step in the workflow sequentially adds value; processes and systems that guarantee work is transparent, efficient and accountable; a model of learning that enables global and local partners to co-create a complex, worldwide community-based learning system in support of entrepreneurship; and a rich network of social relations built from face-to-face and online interactions to help generate social capital needed for development

Maternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring

Summary: Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to increasing prevalence of these diseases, yet mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, and functional levels in bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile offspring and in hematopoietic stem and progenitor cells (HSPCs) from fetal and juvenile bone marrow and fetal liver. mWSD exposure is also associated with increased oleic acid in fetal and juvenile bone marrow and fetal liver. Assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling of HSPCs and BMDMs from mWSD-exposed juveniles supports a model in which HSPCs transmit pro-inflammatory memory to myeloid cells beginning in utero. These findings show that maternal diet alters long-term immune cell developmental programming in HSPCs with proposed consequences for chronic diseases featuring altered immune/inflammatory activation across the lifespan

Author Correction: The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD

An amendment to this paper has been published and can be accessed via a link at the top of the paper.</jats:p

Using Stakeholder Value Analysis to Build Exploration Sustainability

Abstract: The sustainability of space exploration will depend in large part on its ability to consistently and reliably deliver valued benefits to societal stakeholders over an extended period. This on-going research studies the values of prospective stakeholders in the space exploration enterprise—both in the near term and with a perspective extending over decades. The immediate focus is human and robotic exploration of the Earth/Moon system, but extends to the exploration of Mars as well. Potential beneficiaries of space exploration are identified in broad societal sectors. An analysis of these stakeholders, their values and needs leads to the development of a comprehensive set of space exploration objectives that address those needs. The relative priority of exploration objectives is weighted using information about stakeholder characteristics, values, and their role and place in the exploration value stream. The weighted exploration objectives can then be used to assess the relative value of different technical system architectures, and to design exploration enterprise architecture, attributes and policy frameworks to enable value delivery to societal stakeholders. Ultimately, through stakeholders ’ continuing support, sustainable space exploration will be delivered. I