Selectively enhanced contextual fear conditioning in mice lacking the transcriptional regulator CCAAT/enhancer binding protein δ

CCAAT/enhancer binding protein δ (C/EBPδ) is a transcriptional regulator implicated in the hepatic acute phase response and in adipogenic and myeloid cell differentiation. We found that C/EBPδ is widely expressed in the peripheral and central nervous systems, including neurons of the hippocampal formation, indicating a role in neural functions. To examine the role of C/EBPδ in vivo, we generated mice with a targeted deletion of the C/EBPδ gene. This mutation does not interfere with normal embryonic and postnatal development. Performance in a battery of behavioral tests indicates that basic neurological functions are normal. Furthermore, performance in a Morris water maze task suggests that C/EBPδ mutant mice have normal spatial learning. However, in the contextual and auditory-cue-conditioned fear task, C/EBPδ null mice displayed significantly more conditioned freezing to the test context than did wild-type controls, but equivalent conditioning to the auditory cue. These data demonstrate a selectively enhanced contextual fear response in mice carrying a targeted genomic mutation and implicate C/EBPδ in the regulation of a specific type of learning and memory.

Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase

The mechanism by which mutations in the superoxide dismutase (SOD1) gene cause motor neuron degeneration in familial amyotrophic lateral sclerosis (ALS) is unknown. Recent reports that neuronal death in SOD1-familial ALS is apoptotic have not documented activation of cell death genes. We present evidence that the enzyme caspase-1 is activated in neurons expressing mutant SOD1 protein. Proteolytic processing characteristic of caspase-1 activation is seen both in spinal cords of transgenic ALS mice and neurally differentiated neuroblastoma (line N2a) cells with SOD1 mutations. This activation of caspase-1 is enhanced by oxidative challenge (xanthine/xanthine oxidase), which triggers cleavage and secretion of the interleukin 1β converting enzyme substrate, pro-interleukin 1β, and induces apoptosis. This N2a culture system should be an instructive in vitro model for further investigation of the proapoptotic properties of mutant SOD1.

Specific down-regulation of an engineered human cyclin D1 promoter by a novel DNA-binding ligand in intact cells

Cyclin D1 is expressed at abnormally high levels in many cancers and has been specifically implicated in the development of breast cancer. In this report we have extensively analyzed the cyclin D1 promoter in a variety of cancer cell lines that overexpress the protein and identified two critical regulatory elements (CREs), a previously identified CRE at –52 and a novel site at –30. In vivo footprinting experiments demonstrated factors binding at both sites. We have used a novel DNA-binding ligand, GL020924, to target the site at –30 (–30–21) of the cyclin D1 promoter in MCF7 breast cancer cells. A binding site for this novel molecule was constructed by mutating 2 bp of the wild-type cyclin D1 promoter at the –30–21 site. Treatment with GL020924 specifically inhibited expression of the targeted cyclin D1 promoter construct in MCF7 cells in a concentration-dependent manner, thus validating the –30–21 site as a target for minor groove-binding ligands. In addition, this result validates our approach to regulating the expression of genes implicated in disease by targeting small DNA-binding ligands to key regulatory elements in the promoters of those genes.

CA1-specific N-methyl-d-aspartate receptor knockout mice are deficient in solving a nonspatial transverse patterning task

In both humans and animals, the hippocampus is critical to memory across modalities of information (e.g., spatial and nonspatial memory) and plays a critical role in the organization and flexible expression of memories. Recent studies have advanced our understanding of cellular basis of hippocampal function, showing that N-methyl-d-aspartate (NMDA) receptors in area CA1 are required in both the spatial and nonspatial domains of learning. Here we examined whether CA1 NMDA receptors are specifically required for the acquisition and flexible expression of nonspatial memory. Mice lacking CA1 NMDA receptors were impaired in solving a transverse patterning problem that required the simultaneous acquisition of three overlapping odor discriminations, and their impairment was related to an abnormal strategy by which they failed to adequately sample and compare the critical odor stimuli. By contrast, they performed normally, and used normal stimulus sampling strategies, in the concurrent learning of three nonoverlapping concurrent odor discriminations. These results suggest that CA1 NMDA receptors play a crucial role in the encoding and flexible expression of stimulus relations in nonspatial memory.

Skp2 is oncogenic and overexpressed in human cancers

Skp2 is a member of the F-box family of substrate-recognition subunits of SCF ubiquitin–protein ligase complexes that has been implicated in the ubiquitin-mediated degradation of several key regulators of mammalian G1 progression, including the cyclin-dependent kinase inhibitor p27, a dosage-dependent tumor suppressor protein. In this study, we examined Skp2 and p27 protein expression by immunohistochemistry in normal oral epithelium and in different stages of malignant oral cancer progression, including dysplasia and oral squamous cell carcinoma. We found that increased levels of Skp2 protein are associated with reduced p27 in a subset of oral epithelial dysplasias and carcinomas compared with normal epithelial controls. Tumors with high Skp2 (>20% positive cells) expression invariably showed reduced or absent p27 and tumors with high p27 (>20% positive cells) expression rarely showed Skp2 positivity. Increased Skp2 protein levels were not always correlated with increased cell proliferation (assayed by Ki-67 staining), suggesting that alterations of Skp2 may contribute to the malignant phenotype without affecting proliferation. Skp2 protein overexpression may lead to accelerated p27 proteolysis and contribute to malignant progression from dysplasia to oral epithelial carcinoma. Moreover, we also demonstrate that Skp2 has oncogenic potential by showing that Skp2 cooperates with H-RasG12V to malignantly transform primary rodent fibroblasts as scored by colony formation in soft agar and tumor formation in nude mice. The observations that Skp2 can mediate transformation and is up-regulated during oral epithelial carcinogenesis support a role for Skp2 as a protooncogene in human tumors.

Postmortem/postpartum : the intersection between fertility and Mochican ancestral power

With no written record, the religious beliefs of the Pre-Columbian Mochica civilization are much of a mystery. This paper attempts to decipher the position of the deceased Mochicans, also known as ancestors, within the society as a whole. It discusses the ways in which we can use multiple sources of information, archaeological, iconographic, ethnohistoric and ethnographic to learn about the various aspects of Mochican culture. Specifically I will use these methods for collecting data to examine at how the Mochica viewed their deceased and to argue that part of the Mochica religious system granted their dead a supernatural ability to control human and agricultural fertility. This power would give Mochican ancestors a significant place within the society.

Environmental Information Access as a Security Risk

The United Sates was founded on the principles of freedom. Events in recent history have threatened the freedoms we as individuals enjoy. Notably, changes to government legislation and policies regarding access to environmentally sensitive information following September 11, 2001, are troubling. The government has struggled with a difficult balancing act. The public has the right of access to information, yet, information some view as sensitive or dangerous must be kept out of the hands of terrorists. This project examines and discusses the information access debate within the United States and how to best provide the public environmentally sensitive information.

Troubled Waters Ahead: An Evaluation of Shoreline Land Use Policies for Water Quality Protection in Renfrew County, Ontario

Increases in the rate and extent of lakeshore development along inland lakes in Ontario are adversely impacting water quality. Despite growing awareness, there is a lack of knowledge about the land use policies and tools in place to protect inland lakes in rural Ontario. This research evaluated official plans for water quality protection policies for inland lakes in the County of Renfrew, Ontario to address this gap. The findings suggest that municipalities implicitly link water quality to land use planning policy and fail to incorporate innovative methods to protect water quality.

National Visions of EU Defence Policy - Common Denominators and Misunderstandings. CEPS Paperbacks. December 2013

The premise of this study is simple: before discussing what defence strategy the EU should adopt at Brussels-level, member states should clarify what they expect individually from the EU Common Security and Defence Policy (CSDP). Inspired by the confusion about EU defence policy in most European capitals, this authoritative study inverts the usual analytical approach applied to the debate on European strategy. Rather than initiating the enquiry from the perspective of common interests guiding CSDP, it analyses how seven prominent member states see CSDP as a tool to pursue their strictly national interests. Five researchers immersed themselves in the foreign policy worlds of Paris, London, Berlin, Rome, Warsaw, Stockholm and Madrid, looking at CSDP through national lenses and away from the potentially distorting influence of ‘Brussels’ rhetoric.

A 20 m spatial resolution seamless multisource Digital Elevation/Depth Model for Lizard Island, northern Great Barrier Reef

Hydrographers have traditionally referred to the nearshore area as the "white ribbon" area due to the challenges associated with the collection of elevation data in this highly dynamic transitional zone between terrestrial and marine environments. Accordingly, available information in this zone is typically characterised by a range of datasets from disparate sources. In this paper we propose a framework to 'fill' the white ribbon area of a coral reef system by integrating multiple elevation and bathymetric datasets acquired by a suite of remote-sensing technologies into a seamless digital elevation model (DEM). A range of datasets are integrated, including field-collected GPS elevation points, terrestrial and bathymetric LiDAR, single and multibeam bathymetry, nautical chart depths and empirically derived bathymetry estimations from optical remote sensing imagery. The proposed framework ranks data reliability internally, thereby avoiding the requirements to quantify absolute error and results in a high resolution, seamless product. Nested within this approach is an effective spatially explicit technique for improving the accuracy of bathymetry estimates derived empirically from optical satellite imagery through modelling the spatial structure of residuals. The approach was applied to data collected on and around Lizard Island in northern Australia. Collectively, the framework holds promise for filling the white ribbon zone in coastal areas characterised by similar data availability scenarios. The seamless DEM is referenced to the horizontal coordinate system MGA Zone 55 - GDA 1994, mean sea level (MSL) vertical datum and has a spatial resolution of 20 m.

2000 UM Women's Tennis Team

University of Michigan Women's Cross Country Team, 1990

Back Row: coach Sue Foster, Jen Armstrong, Kim Haluscsak, Amy Bannister, Megan Nortz, Chris Szabo, Molly McClimon

Front Row: Jessica Kluge, Kristi McKimson, Jen Keil, Amy Bucholz, Chris Tyler,

University of Michigan Women's Cross Country Team, 1991

Back Row: head coach Sue Foster, Amy Bucholz, Kate Jackson, Kelly Chard, Courtney Babcock, Jennifer Kiel, Kristine Westerby. Jenny Stuht, Kathie Nordquist, Michelle Radcliffe

Front Row: Chris Szabo, Mayrie Richards, Kristi Wink, Megan Nortz, Jessica Kluge, Karen Harvey, Carrie Yates, Rachel Mann (not pictured: Molly McClimon)

Women's Volleyball Team, 2003 UM

Front Row: Front) Angela Mierzwiak (student trainer), Eric Heller (student assistant), Jennifer Gandolph, Candace Gay, Sarah Allen, Lisa Gamalski, Alicia Boswell, Kristina Sabbagh, Danielle Pflum, Sarah Puera (student assistant), Jun Liu (assistant coach).

Back Row: Jason Cole (strength and conditioning), Mark Stoessner (athletic trainer), Megan Bowman, Ashley Buckingham, Erin Moore, Nicole Poquette, Chantel Reedus, Erin Cobler, Leisa Rosen (associate head coach), Mark Rosen (head coach).