Synthetic chemerin-derived peptides suppress inflammation through ChemR23

Chemerin is a chemotactic protein that binds to the G protein-coupled receptor, ChemR23. We demonstrate that murine chemerin possesses potent antiinflammatory properties that are absolutely dependent on proteolytic processing. A series of peptides was designed, and only those identical to specific C-terminal chemerin sequences exerted antiinflammatory effects at picomolar concentrations in vitro. One of these, chemerin15 (C15; A(140)-A(154)), inhibited macrophage (MPhi) activation to a similar extent as proteolyzed chemerin, but exhibited reduced activity as a MPhi chemoattractant. Intraperitoneal administration of C15 (0.32 ng/kg) to mice before zymosan challenge conferred significant protection against zymosan-induced peritonitis, suppressing neutrophil (63%) and monocyte (62%) recruitment with a concomitant reduction in proinflammatory mediator expression. Importantly, C15 was unable to ameliorate zymosan-induced peritonitis in ChemR23(-/-) mice, demonstrating that C15's antiinflammatory effects are entirely ChemR23 dependent. In addition, administration of neutralizing anti-chemerin antibody before zymosan challenge resulted in a significant exacerbation of peritoneal inflammation (up to 170%), suggesting an important endogenous antiinflammatory role for chemerin-derived species. Collectively, these results show that chemerin-derived peptides may represent a novel therapeutic strategy for the treatment of inflammatory diseases through ChemR23.     

Disparities in mammography use among US women aged 40-64 years, by race, ethnicity, income, and health insurance status, 1993 and 2005

OBJECTIVE: To examine current disparities in mammography use, and changes in disparities over time by race, ethnicity, income, insurance, and combinations of these characteristics. RESEARCH DESIGN: Comparison of cross-sectional surveys of mammography use using the 1993 and 2005 National Health Interview Survey. SUBJECTS: Women aged 40-64 (1993, n = 4167; 2005, n = 7434). MEASURES: Mammogram within prior 2 years. RESULTS: In 2005, uninsured women reported the lowest mammography use (38.3%). Though screening increased 6.9 percentage points among low-income, uninsured women, the overall disparity between insured and uninsured women did not change significantly between 1993 and 2005. Screening seems to have declined among middle-income, uninsured women, increasing the gap compared with middle-income, insured women. The lower mammography use in 1993 among American Indian/Alaska Native compared with white women was not present in 2005; however, lower use among Asian compared with white women emerged in 2005. We found no differences between African American and white women. Hispanic women were less likely than non-Hispanic women to report screening in 2005 (58.1% vs. 69.0%). CONCLUSIONS: Although mammography use increased for some groups between 1993 and 2005, low-income, uninsured women continued to have the lowest screening rates in 2005 and the disparity for this group was not reduced. The gap in screening use for middle-income, uninsured women increased, resulting from possible declines in mammography even for uninsured women not in poverty. Asian women became less likely to receive screening in 2005. Continuing efforts are needed to eliminate disparities. Increased efforts are especially needed to address the large persistent disparity for uninsured women, including middle-income uninsured women.     

An examination of the association between seeing smoking in films and tobacco use in young adults in the west of Scotland: cross-sectional study

The objective is to examine the association between the amount of smoking seen in films and current smoking in young adults living in the west of Scotland in the UK. Cross-sectional analyses (using multivariable logistic regression) of data collected at age 19 (2002-04) from a longitudinal cohort originally surveyed at age 11 (1994-95) were conducted. The main outcome measure is smoking at age 19. No association was found between the number of occurrences of smoking estimated to have been seen in films (film smoking exposure) and current (or ever) smoking in young adults. This lack of association was unaffected by adjustment for predictors of smoking, including education, risk-taking orientation and smoking among peers. There was no association between film smoking exposure and smoking behaviour for any covariate-defined subgroup. Associations have been found between film smoking exposure and smoking initiation in younger adolescents in the United States. In this study, conducted in Scotland, no similar association was seen, suggesting that there may be age or cultural limitations on the effects of film smoking exposure on smoking. The lack of association could be due to methodological issues or greater sophistication of older adolescents and young adults in interpreting media images or the greater ubiquity of real-life smoking instances in Scotland. If the latter, film smoking exposure could become a more important risk factor for smoking uptake and maintenants in older adolescents following the recent ban on smoking in public places in Scotland.     

Palmitoylation of the C-terminal fragment of p75(NTR) regulates death signaling and is required for subsequent cleavage by gamma-secretase

It has recently been shown that the p75 neurotrophin receptor (p75(NTR)), which is known to mediate neural cell death during development of the nervous system and in a range of adult neurodegenerative conditions, undergoes a regulated process of cell surface receptor cleavage, regulated intramembrane proteolysis (RIP). Here we show that neuronal death signaling occurs only following extracellular metalloprotease cleavage of p75(NTR) and palmitoylation of the resultant C-terminal fragment, causing its translocation to cholesterol-rich domains of the plasma membrane. Furthermore, death signaling is promoted by inhibition of intracellular gamma-secretase cleavage, a process which also occurs within the cholesterol-rich domains. In the presence of TrkA signaling, C-terminal fragment localization in these cholesterol-rich domains is prevented, thereby blocking neuronal death. Thus p75(NTR) activates neuronal death pathways in conditions where the balance of normal RIP is shifted toward extracellular domain cleavage due to increased metalloprotease activity, decreased TrkA activity or compromised gamma-secretase activity, all of which are features of neurodegenerative conditions such as Alzheimer's disease.     

Changes in neural activity associated with learning to articulate novel auditory pseudowords by covert repetition

Learning to articulate novel combinations of phonemes that form new words through a small number of auditory exposures is crucial for development of language and our capacity for fluent speech, yet the underlying neural mechanisms are largely unknown. We used functional magnetic resonance imaging to reveal repetition-suppression effects accompanying such learning and reflecting discrete changes in brain activity due to stimulus-specific fine-tuning of neural representations. In an event-related design, subjects were repeatedly exposed to auditory pseudowords, which they covertly repeated. Covert responses during scanning and postscanning overt responses showed evidence of learning. An extensive set of regions activated bilaterally when listening to and covertly repeating novel pseudoword stimuli. Activity decreased, with repeated exposures, in a subset of these areas mostly in the left hemisphere, including premotor cortex, supplementary motor area, inferior frontal gyrus, superior temporal cortex, and cerebellum. The changes most likely reflect more efficient representation of the articulation patterns of these novel words in two connected systems, one involved in the perception of pseudoword stimuli (in the left superior temporal cortex) and one for processing the output of speech (in the left frontal cortex). Both of these systems contribute to vocal learning.     

Lesions of the mammillary body region severely disrupt the cortical head direction, but not place cell signal

The rat limbic system contains a variety of location (place and grid) cells and directional (head direction; HD) cells, thought to be critical for navigation. The HD cells can be found throughout many portions of the hippocampal formation, as well as additional limbic cortical and subcortical regions. These HD-containing regions are generally strongly interconnected anatomically. Earlier work, along with theoretical considerations, suggest that despite the ubiquitous presence of HD cells, there may be a single region which is critical for the initial formation of this HD signal. Specifically, it has been suggested that the critical HD cell network resides in a reciprocal loop formed by the interconnected lateral mammillary nucleus and dorsal tegmental nucleus of Gudden. Unlike the HD cells, place cells have not been observed in subcortical structures. They are, however, found in various forms throughout much of the hippocampal formation. Theoretical accounts of the place cells suggest that they are partly dependent on a path integration process which is, in turn, dependent on the HD cells. According to the above reasoning, lesions of the mammillary bodies should completely eliminate both HD and place/grid cells in the hippocampal formation. Here, we tested for both HD and place cell activity in various hippocampal formation sub regions following lesions of the mammillary bodies. We found that these lesions caused nearly complete elimination of the HD cell signal, but left the place cell signal largely intact. Our interpretation of these findings is somewhat limited by the fact that we did not provide a thorough test of the path integration abilities of the post lesion place cells. These findings pose a challenge for current theoretical accounts of place and grid cells. They also help to explain the role played by the mammillary bodies in spatial learning and memory.     

Internalization of the ultra-thin ideal: positive implicit associations with underweight fashion models are associated with drive for thinness in young women

This study examined whether young women who make implicit associations between underweight models and positive attributes report elevated eating disorder symptoms. Ninety nine female undergraduates completed a weight based implicit association test (IAT) and self report measures of body dissatisfaction, thin-ideal internalization and eating disorder symptoms. IAT scores were associated with drive for thinness (r = -0.26, p < 0.05). This relationship was moderated by attitude importance. The relationship between drive for thinness and IAT scores was stronger (r = 0.34; p < 0.02) in participants who report that the media is an important source of information about fashion and being attractive. The IAT used in the current study is sensitive enough to discriminate between participants on drive for thinness. Women who have developed cognitive schemas that associate being underweight with positive attributes report higher eating disorder symptoms. Attitude importance is highlighted as a key construct in thin ideal internalization.     

The employment intervention demonstration program: major findings and policy implications

This article summarizes the published results of the Employment Intervention Demonstration Program (EIDP), a federally-funded, multi-site study examining the effectiveness of supported employment programs for 1273 unemployed individuals with psychiatric disabilities in the U.S. Findings confirm the effectiveness of supported employment across different models, program locations, and participant populations. The study's results are discussed in the context of public policies designed to encourage return to work for those with a severe mental illness.     

A New Computerised Advanced Theory of Mind Measure for Children with Asperger Syndrome: The ATOMIC

This study examined the ability of children with Asperger Syndrome (AS) to attribute mental states to characters in a new computerised, advanced theory of mind measure: The Animated Theory of Mind Inventory for Children (ATOMIC). Results showed that children with AS matched on IQ, verbal comprehension, age and gender performed equivalently on central coherence questions, but more poorly on the theory of mind questions compared with controls. A significant relationship was found between performance on ATOMIC and accuracy of mental state explanations provided on (Happé’s, Journal of Autism and Developmental Disorders, 24, 129–154, 1994) Strange Stories Task, supporting the validity of the new measure. Limitations of the study and suggestions for future research are discussed.     

Confabulation: a spontaneous and fantastic review

Confabulation can be of two types: provoked or spontaneous. The former is the more common and can occur on challenge to an amnesic patient's memory. Spontaneous confabulation involves an unprovoked outpouring of unbelievable autobiographical claims. The purpose of the present paper is to synthesize the current literature on confabulation for the use of treating clinicians. There is a focus on the spontaneous form, which is less common, but more memorable when encountered. In this paper the history, phenomenology, incidence, anatomical underpinnings and theoretical mechanisms of spontaneous confabulations will be reviewed, and then the paper will conclude by addressing prognostic and treatment issues. A systematic literature review of electronic databases was conducted to identify the key articles, reviews and books that have shaped the understanding of spontaneous confabulation.