Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis

BACKGROUND: The human psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/psoriasin in skin inflammation and mammary tumorigenesis. METHODS: On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7. RESULTS: Although mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene. CONCLUSION: These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression

Patchwork neighborhood: children’s urban geographies in Buffalo, New York

The West Side of the City of Buffalo, New York, is a neighborhood in racial and ethnic transition, demographically. However, at any given time it represents a snapshot of a geographic area that is diverse economically, ethnically, and racially, and in terms of its built environment. I use the notion of ‘patchwork’ first as a literal interpretation based on a quilting project I facilitated with children from an after-school program in this location. Second, ‘patchwork’ is used as a metaphor capturing results of neighborhood explorations led by the children over three years (2003 – 06). Specifically, as I explore children’s perceptions of ‘neighborhood’, the notion of ‘patchwork’ seems to accommodate their varied understandings, views, and perspectives of their neighborhoods well. Simultaneously, the notion also contributes to the fluid and active construction of the term in urban geography.

Grounded visualization: integrating the analysis of qualitative and quantitative data through grounded theory and visualization

Our purpose in this paper is to conceptualize and demonstrate an integrated analytical method for using both qualitative and quantitative data through geographic information systems (GIS) and ethnography. We acknowledge that the use of both types of data has been possible in GIS for some time, particularly for representation purposes. However, a recursive integration of different forms of data at the analysis level has been less explored and minimally theorized. Drawing on recent work in critical GIS and feminist perspectives, we suggest that visualization offers a strong technique for this effort but we approach it from the analytical base of grounded theory. Thus, we present an example of how grounded theory and visualization might be used together to construct an integrated analysis strategy that is both iterative and reflexive, both contextual and conceptual. We use Knigge’s work on community gardens in Buffalo, New York, to provide a substantive example of the proposed methods.

Sex differences in distributed error-related neural activation in binge drinking young adults

Background: Detecting and responding to errors is central to goal-directed behavior and cognitive control and is thought to be supported by a network of structures that includes the anterior cingulate cortex and anterior insula. Sex differences in the maturational timing of cognitive control systems create differential periods of vulnerability for psychiatric conditions, such as substance use disorders, between males and females. Methods: We examined sex differences in error-related activation across an array of distributed brain regions during a Go/No-Go task in young adults with problem alcohol use (N=69; 34 females; mean age 19.4 years). Regions of interest previously linked to error-related activation, including the anterior cingulate cortex (ACC), insula, and frontoparietal structures, were selected in a term-based meta-analysis, and individual differences in their activation were indexed using a multivariate summary measure. Results: Males exhibited significantly higher levels of this multivariate summary measure in error-related activation than females. These results were supported by a whole brain search in which males had greater activity in left and right prefrontal areas, including ACC and insula, as well as bilateral thalamus. Conclusions: The findings that males have higher responses to errors across a network of regions linked to performance monitoring and cognitive control could ultimately be used for more targeted cognitive-based substance use interventions

Brain activation to negative stimuli mediates a relationship between adolescent marijuana use and later emotional functioning

This work investigated the impact of heavy marijuana use during adolescence on emotional functioning, as well as the brain functional mediators of this effect. Participants (n = 40) were recruited from the Michigan Longitudinal Study (MLS). Data on marijuana use were collected prospectively beginning in childhood as part of the MLS. Participants were classified as heavy marijuana users (n = 20) or controls with minimal marijuana use. Two facets of emotional functioning—negative emotionality and resiliency (a self-regulatory mechanism)—were assessed as part of the MLS at three time points: mean age 13.4, mean age 19.6, and mean age 23.1. Functional neuroimaging data during an emotion-arousal word task were collected at mean age 20.2. Negative emotionality decreased and resiliency increased across the three time points in controls but not heavy marijuana users. Compared with controls, heavy marijuana users had less activation to negative words in temporal, prefrontal, and occipital cortices, insula, and amygdala. Activation of dorsolateral prefrontal cortex to negative words mediated an association between marijuana group and later negative emotionality. Activation of the cuneus/lingual gyrus mediated an association between marijuana group and later resiliency. Results support growing evidence that heavy marijuana use during adolescence affects later emotional outcomes

Sex differences in neural responsivity to reward and loss: Associations with triarchic model traits and antisocial behavior

Deficits in response to reward and loss are implicated in antisocial personality disorder (ASPD) and psychopathy. This study examined sex differences in associations of neural response to reward and loss with triarchic model traits and ASPD symptoms. Functional neuroimaging data was collected during a monetary incentive delay task from 158 participants. We predicted that males high in ASPD would show greater neural response to reward anticipation and less neural response to loss. Analyses examining the triarchic model were exploratory. A significant sex by Boldness interaction was associated with left nucleus accumbens response during loss anticipation. There were also significant sex by ASPD associations with left nucleus accumbens and left amygdala activation during the loss feedback condition and left nucleus accumbens during loss anticipation. These results demonstrate the importance of considering the effects of sex and triarchic model traits when examining reward and loss processing in the context of antisocial behavior

Nucleus Accumbens Response to Reward among Children with a Family History of Alcohol Use Problems: Convergent Findings from the ABCD Study® and Michigan Longitudinal Study

Having a family history of alcohol use problems (FH+) conveys risk for alcohol use in offspring. Reward-related brain functioning may play a role in this vulnerability. The present study investigated brain function in the nucleus accumbens (NAcc) associated with the anticipation of reward in youth with two biological parents with alcohol use problems (FH+2), one biological parent with alcohol use problems (FH+1), and no biological parents with alcohol use problems (FH-). Participants were from the large, national Adolescent Brain Cognitive Development (ABCD) Study (mean age: 9.93; 48% female; FH+2 n = 223, FH+1 n = 1447, FH- n = 9690) and the Michigan Longitudinal Study (MLS), consisting of community-recruited families with high rates of alcohol use disorder (mean age: 10.54; 39.3% female; FH+2 n = 40, FH+1 n = 51, FH- n = 40). Reward anticipation was measured by the monetary incentive delay task. Regression models were used to assess associations between FH status and the anticipation of large rewards in right and left NAcc regions of interest. In both studies, FH+2 youth showed blunted anticipatory reward responding in the right NAcc compared to FH+1 youth. In the MLS, FH+2 youth also had blunted anticipatory reward responding in the right NAcc compared to the FH- group. Convergent results across two separate samples provide insights into a unique vulnerability of FH+2 youth and suggest that binary FH+ versus FH- categorizations may obscure important differences within FH+ youth