Comparing body image dissatisfaction between pregnant women and non-pregnant women: a systematic review and meta-analysis.

Body image dissatisfaction refers to negative thoughts and feelings individuals have towards their own body appearance and this is thought to be affected by the physiological changes that occur during pregnancy. There are two main conflicting theories as to the effect pregnancy has on body image dissatisfaction: 1) Pregnancy related changes are in direct conflict with social ideas of female beauty (e.g. weight gain) and so increase body image dissatisfaction; 2) Due to changes in expectations of bodily appearance during pregnancy, women are liberated from social ideals at this time and thus body image dissatisfaction would decrease. This study aimed to assess these theories by synthesising the current literature. Six databases were searched, and 2,017 study abstracts were screened based on strict inclusion and exclusion criteria. Following screening and quality assessment by two blind reviewers, 17 studies (comprising 17 effect sizes) were subject to full review and meta-analysis following PRISMA guidelines. These studies included cross-sectional, longitudinal and retrospective designs. Results varied with some studies showing women to feel more positive about their body during pregnancy, others showing a more negative body experience and yet others showing no statistical difference. Overall the analysis showed no statistical difference in body image dissatisfaction between pregnant women and non-pregnant women (p = 0.39). Any changes that do occur are heterogeneous and likely to be largely dependent on the individual experience as well as moderator variables and other factors such as differences in methodology of research studies. Studies in this field of research would benefit from more explicit and complete reporting of data and key variables, in order to allow early intervention for women who display body image dissatisfaction in pregnancy.

Exploring the development of high-level contributions to body representation using the rubber hand illusion and the monkey hand illusion.

During development our body undergoes significant changes, yet we are able to maintain a coherent experience of our body and sense of self. Bodily experience is thought to comprise integration of multisensory signals (vision, touch, and proprioception) constrained by top-down knowledge of body appearance. Evidence from developmental studies suggests that low-level multisensory integration develops throughout childhood, reaching adult levels by 10 years of age. However, how high-level cognitive knowledge changes during childhood to constrain our multisensory body experience is unknown. This study describes four experiments examining high-level contributions to the bodily experience in children compared with adults using the rubber hand illusion and a monkey hand illusion. We found that children (5-17 years of age) exhibited more flexible body representations, showing stronger illusions for small and fantastical (monkey) fake hands compared with adults. Conversely, using a task indirectly capturing changes in hand size, we found that children and adults demonstrated statistically equivalent increases and decreases in hand size following illusions over large and small hands, respectively. Interestingly, at baseline children showed a bias in reporting larger hand size judgments that decreased with age. Finally, we did not find a relationship between individual differences in fantasy proneness and illusion strength for a fantastical (monkey) hand for children or adults, suggesting that developmental changes of top-down constraints are not purely driven by more diffuse boundaries between imagination and reality. These data suggest that high-level constraints acting on our multisensory body experience change during development, allowing children a more flexible bodily experience compared with adults.

Gesture Facilitates Children's Creative Thinking.

Gestures help people think and can help problem solvers generate new ideas. We conducted two experiments exploring the self-oriented function of gesture in a novel domain: creative thinking. In Experiment 1, we explored the relationship between children's spontaneous gesture production and their ability to generate novel uses for everyday items (alternative-uses task). There was a significant correlation between children's creative fluency and their gesture production, and the majority of children's gestures depicted an action on the target object. Restricting children from gesturing did not significantly reduce their fluency, however. In Experiment 2, we encouraged children to gesture, and this significantly boosted their generation of creative ideas. These findings demonstrate that gestures serve an important self-oriented function and can assist creative thinking.

Genetic determinants of atherosclerosis, obesity, and energy balance in consomic mice.

Metabolic diseases such as obesity and atherosclerosis result from complex interactions between environmental factors and genetic variants. A panel of chromosome substitution strains (CSSs) was developed to characterize genetic and dietary factors contributing to metabolic diseases and other biological traits and biomedical conditions. Our goal here was to identify quantitative trait loci (QTLs) contributing to obesity, energy expenditure, and atherosclerosis. Parental strains C57BL/6 and A/J together with a panel of 21 CSSs derived from these progenitors were subjected to chronic feeding of rodent chow and atherosclerotic (females) or diabetogenic (males) test diets, and evaluated for a variety of metabolic phenotypes including several traits unique to this report, namely fat pad weights, energy balance, and atherosclerosis. A total of 297 QTLs across 35 traits were discovered, two of which provided significant protection from atherosclerosis, and several dozen QTLs modulated body weight, body composition, and circulating lipid levels in females and males. While several QTLs confirmed previous reports, most QTLs were novel. Finally, we applied the CSS quantitative genetic approach to energy balance, and identified three novel QTLs controlling energy expenditure and one QTL modulating food intake. Overall, we identified many new QTLs and phenotyped several novel traits in this mouse model of diet-induced metabolic diseases.

Bonding with bump: Interoceptive sensibility moderates the relationship between pregnancy body satisfaction and antenatal attachment.

PROBLEM: There is limited understanding and contradictory results regarding the contribution of the pregnant bodily experience to antenatal attachment. BACKGROUND: Antenatal attachment is an important aspect of pregnancy, which has been linked with positive maternal and infant outcomes. Given the profound physical process of pregnancy, it is likely that bodily experience is implicated in antenatal attachment, with research supporting the involvement of pregnancy body (dis)satisfaction. However, previous research reveals conflicting results and has only focused on exteroceptive bodily experience (appearance) rather than internal physiological sensations (interoception). AIM: To examine the relative contributions of both external and internal bodily experience in antenatal attachment. METHODS: This cross-sectional study collected online survey data from 159 pregnant participants with measures capturing interoceptive sensibility (subjective experience of interoception), pregnancy body dissatisfaction and antenatal attachment. FINDINGS: We replicated previous findings that pregnancy body dissatisfaction is related to antenatal attachment. However, the relationship between pregnancy body dissatisfaction and antenatal attachment was moderated by worry about interoceptive signals. The interoceptive construct of body trust was most strongly associated with antenatal attachment. DISCUSSION: The results suggest that interoception is important for antenatal attachment, particularly feelings of body trust. Moreover, for individuals who were less worried about bodily sensations, high levels of body dissatisfaction were associated with low attachment scores, whilst for those who were more concerned about these sensations, the relationship between body dissatisfaction and antenatal attachment was mitigated. CONCLUSION: The results suggest that focusing on internal sensations may be a protective strategy against pregnancy body dissatisfaction to strengthen maternal bonds.

Body understanding measure for pregnancy scale (BUMPs): Cross-cultural adaptation and psychometric properties among Brazilian pregnant women.

The Body Understanding Measure for Pregnancy Scale (BUMPs) is a scale developed and validated for British pregnant women to assess body satisfaction during pregnancy. The aim of this study was to perform a cross-cultural adaptation and verify the psychometric properties of BUMPs for Brazilian adult pregnant women. The cross-cultural adaptation was performed using translation, back-translation, expert committee, expert analysis, and pre-testing, which showed easy comprehension by pregnant women. Psychometric analyses were evaluated in a sample of 618 pregnant women (31.08 ± 4.94 years old). Exploratory and confirmatory factor analyses resulted in 19 items and three factors, with satisfactory fit indices. BUMPs presented an invariant measurement across white vs. nonwhite women and across the three gestational trimesters. BUMPs showed good indicators of convergent, internal consistency, and test-retest reproducibility validity. It was concluded that the Brazilian version of BUMPs has adequate psychometric properties for Brazilian pregnant women, being an excellent instrument for analyzing body satisfaction in this population, facilitating additional investigations into these constructs.

To sign or not to sign? The impact of encouraging infants to gesture on infant language and maternal mind-mindedness.

Findings are presented from the first randomized control trial of the effects of encouraging symbolic gesture (or "baby sign") on infant language, following 40 infants from age 8 months to 20 months. Half of the mothers were trained to model a target set of gestures to their infants. Frequent measures were taken of infant language development and dyadic interactions were scrutinized to assess mind-mindedness. Infants exposed to gesture did not differ from control conditions on language outcomes; thus, no support was found for previous claims that encouraging gesturing with infants accelerates linguistic development. Microgenetic analysis revealed mothers in the gesture training conditions were more responsive to their infants' nonverbal cues and encouraged more independent action by their infant.

Exercise, physical activity and breast cancer: the role of tumor-associated macrophages.

Regular exercise and physical activity provide many health benefits and are encouraged by medical professionals for the primary prevention of and adjuvant treatment of breast cancer Current consensus in the discipline of exercise oncology is that both regular physical activity and exercise training exert some protective effect against breast cancer risk, and may reduce morbidity in some advanced cases. While there is growing interest in the role of exercise and physical activity in breast cancer prevention, it is currently unclear how exercise may modulate tumor behavior. The tumor microenvironment is populated by stromal cells such as fibroblasts and adipocytes, as well as macrophages. Termed tumor-associated macrophages (TAMs), these immune cells are highly plastic and respond to different signals from the cancer microenvironment, causing them to either display tumor-promoting or tumor-suppressing phenotypes. Because of such plasticity, there has been considerable interest by immunologists to develop immunotherapies based on skewing the behavior of TAMs to become cancer-suppressive. Previous studies have indirectly shown the ability of exercise training to induce an anti-tumor effect of macrophages, although the studies did not address this in the tumor microenvironment. Nevertheless, this opens up the possibility that regular exercise training may exert a protective innate immune effect against breast cancer, potentially by inducing a cancer-suppressing phenotype of TAMs. This review will describe potential mechanisms through which exercise may modulate the behavior of TAMs.

Interoceptive sensibility and body satisfaction in pregnant and non-pregnant women with and without children.

Pregnancy is a time of great physical and psychological change. As well as prominent changes in the external appearance of the body, such as the baby bump, there are also substantial changes taking place within the body. Our awareness of, and attention towards, internal bodily signals (interoception) is thought to have a direct impact on how we feel about our bodies. Therefore, understanding how our experience of these interoceptive signals might change during pregnancy may have important implications for maternal wellbeing. This study examined body satisfaction and interoceptive sensibility (subjective experience of interoception) in pregnant and non-pregnant women with and without children. Feelings towards pregnancy-specific changes in body satisfaction and interoceptive sensibility were also examined in women in their first pregnancy (primigravida) and subsequent pregnancies (multigravida). It was found that pregnancy did not directly impact levels of body satisfaction, instead pregnant and non-pregnant women with children reported less satisfaction with their bodies compared to those without children. Primigravida women were more satisfied with the appearance of pregnancy specific bodily changes compared to multigravida women. Interestingly, these differences in body satisfaction in those with children (pregnant and non-pregnant) were mediated by the extent to which women trusted their bodies (measure of interoceptive sensibility). All other pregnancy related changes in interoceptive sensibility and body satisfaction were either non-significant or had small effect sizes. These results may suggest body trust as an important factor to support during the transition to parenthood in order to improve body satisfaction in mothers.

Roles for cathepsins S, L, and B in insulitis and diabetes in the NOD mouse.

We developed a panel of non-obese diabetic (NOD) mice deficient in major lysosomal cysteine proteases (cathepsins S, L and B) to identify protease enzymes essential for autoimmune diabetes. Null alleles for cathepsins (Cts) S, L or B were introgressed onto the NOD genetic background with 19 Idd markers at homozygosity. Diabetes onset was determined among females aged up to 6 months. We evaluated insulitis and sialadenitis in tissues using histology and computer assisted morphology. NOD mice deficient in Ctss or Ctsb were partially protected from diabetes with incidence at 33% and 28%, respectively, versus wild-type NOD (69%; p < 0.00001). NODs lacking cathepsin L (Ctsl-/-) are completely protected from IDDM, as originally shown by others. Ctsl, Ctss, or Ctsb heterozygous mice were able to develop IDDM, although incidence levels were significantly lower for Ctsb+/- (50%) and Ctsl+/- (55%) as compared to NODs (69%; p < 0.03). Ctsl-/- mice contain functional, diabetogenic T cells and an enriched Foxp3+ regulatory T cell population, and diabetes resistance was due to the presence of an expanded population of regulatory T cells. These data provide additional information about the potency of the diabetogenic T cell population in Ctsl-/- mice which were comparable in potency to wild-type NOD mice. These data illustrate the critical contribution of each of these proteases in determining IDDM in the NOD mouse and provide a useful set of models for further studies.

Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice.

OBJECTIVE: Chronic systemic inflammation accompanies obesity and predicts development of cardiovascular disease. Dietary cholesterol has been shown to increase inflammation and atherosclerosis in LDL receptor-deficient (LDLR(-/-)) mice. This study was undertaken to determine whether dietary cholesterol and obesity have additive effects on inflammation and atherosclerosis. METHODS AND RESULTS: LDLR(-/-) mice were fed chow, high-fat, high-carbohydrate (diabetogenic) diets without (DD) or with added cholesterol (DDC) for 24 weeks. Effects on adipose tissue, inflammatory markers, and atherosclerosis were studied. Despite similar weight gain between DD and DDC groups, addition of dietary cholesterol increased insulin resistance relative to DD. Adipocyte hypertrophy, macrophage accumulation, and local inflammation were observed in intraabdominal adipose tissue in DD and DDC, but were significantly higher in the DDC group. Circulating levels of the inflammatory protein serum amyloid A (SAA) were 4.4-fold higher in DD animals and 15-fold higher in DDC animals than controls, suggesting chronic systemic inflammation. Hepatic SAA mRNA levels were similarly elevated. Atherosclerosis was increased in the DD-fed animals and further increased in the DDC group. CONCLUSIONS: Obesity-induced macrophage accumulation in adipose tissue is exacerbated by dietary cholesterol. These local inflammatory changes in adipose tissue are associated with insulin resistance, systemic inflammation, and increased atherosclerosis in this mouse model.

Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance.

OBJECTIVE: Obesity causes inflammation and insulin resistance in the vasculature as well as in tissues involved in glucose metabolism such as liver, muscle, and adipose tissue. To investigate the relative susceptibility of vascular tissue to these effects, we determined the time course over which inflammation and insulin resistance develops in various tissues of mice with diet-induced obesity (DIO) and compared these tissue-based responses to changes in circulating inflammatory markers. METHODS AND RESULTS: Adult male C57BL/6 mice were fed either a control low-fat diet (LF; 10% saturated fat) or a high-fat diet (HF, 60% saturated fat) for durations ranging between 1 to 14 weeks. Cellular inflammation and insulin resistance were assessed by measuring phospho-IkappaBalpha and insulin-induced phosphorylation of Akt, respectively, in extracts of thoracic aorta, liver, skeletal muscle, and visceral fat. As expected, HF feeding induced rapid increases of body weight, fat mass, and fasting insulin levels compared to controls, each of which achieved statistical significance within 4 weeks. Whereas plasma markers of inflammation became elevated relatively late in the course of DIO (eg, serum amyloid A [SAA], by Week 14), levels of phospho-IkappaBalpha in aortic lysates were elevated by 2-fold within the first week. The early onset of vascular inflammation was accompanied by biochemical evidence of both endothelial dysfunction (reduced nitric oxide production; induction of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1) and insulin resistance (impaired insulin-induced phosphorylation of Akt and eNOS). Although inflammation and insulin resistance were also detected in skeletal muscle and liver of HF-fed animals, these responses were observed much later (between 4 and 8 weeks of HF feeding), and they were not detected in visceral adipose tissue until 14 weeks. CONCLUSIONS: During obesity induced by HF feeding, inflammation and insulin resistance develop in the vasculature well before these responses are detected in muscle, liver, or adipose tissue. This observation suggests that the vasculature is more susceptible than other tissues to the deleterious effects of nutrient overload.

Development and validation of the Body Understanding Measure for Pregnancy Scale (BUMPS) and its role in antenatal attachment.

Pregnancy is a unique period in a woman's life during which her body undergoes rapid and dramatic change. Many of these changes are in direct conflict to social ideals of female body appearance, such as increases in body size and weight. Existing research that has examined body satisfaction in pregnancy is limited by the use of measures that are not designed for pregnancy, yielding biased results. Two studies have attempted to develop measures for pregnancy but have used suboptimal sample sizes and/or have not fully validated the measure with independent samples. We seek to address these limitations in the current study and report the development and validation of the newly developed Body Understanding Measure for Pregnancy scale (BUMPs) in 613 pregnant women across two independent samples. Exploratory factor analysis revealed three factors; satisfaction with appearing pregnant, weight gain concerns, and physical burdens of pregnancy, which were confirmed with confirmatory factor analysis. Multiple Indicators Multiple Causes (MIMIC) modeling indicated the scale is appropriate for women in all three trimesters of pregnancy. Evidence of internal reliability, test-retest reliability and convergent validity provide excellent psychometric support. We further demonstrated construct validity by supporting 3 hypotheses, finding that more positive body satisfaction in pregnancy was related to: (a) better relationship quality; (b) lower depression and anxiety; (c) higher levels of interoception, specifically body listening, and body trusting. Additionally, we present evidence that BUMPs score was the strongest predictor of antenatal attachment when compared against depression, anxiety, gestational age, and relationship satisfaction. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The mindedness of maternal touch: An investigation of maternal mind-mindedness and mother-infant touch interactions.

Increasing evidence shows that maternal touch may promote emotion regulation in infants, however less is known about how parental higher-order social cognition abilities are translated into tactile, affect-regulatory behaviours towards their infants. During 10 min book-reading, mother-infant sessions when infants were 12 months old (N = 45), we investigated maternal mind-mindedness (MM), the social cognitive ability to understand an infant's mental state, by coding the contingency of maternal verbal statements towards the infants' needs and desires. We also rated spontaneous tactile interactions in terms of their emotional contingency. We found that frequent non-attuned mind-related comments were associated with touch behaviours that were not contingent with the infant's emotions; ultimately discouraging affective tactile responses from the infant. However, comments that were more appropriate to infant's mental states did not necessarily predict more emotionally-contingent tactile behaviours. These findings suggest that when parental high-order social cognitive abilities are compromised, they are also likely to translate into inappropriate, tactile attempts to regulate infant's emotions.

Modulation of diabetes in NOD mice by GAD65-specific monoclonal antibodies is epitope specific and accompanied by anti-idiotypic antibodies.

Type 1 diabetes is caused by the autoimmune destruction of pancreatic beta cells. Here we show that administration of a human monoclonal antibody (b96.11) specific to the 65-kDa isoform of glutamate decarboxylase (GAD65) to prediabetic non-obese diabetic (NOD) mice significantly delays the onset of autoimmune diabetes. We found this effect to be epitope-specific, as only b96.11 showed this therapeutic property, while a GAD65-specific human monoclonal control antibody (b78) derived from the same patient, but specific to a different determinant of GAD65, had no significant effect on the progression of disease. Administration of b96.11 or b78 to NOD mice was accompanied by the generation of anti-idiotypic antibodies. Importantly, the induced anti-idiotypic antibodies were specific for the immunizing antibody and blocked the binding of GAD65 by the respective antibody. These findings suggest a potential role for the internal image of the GAD65 determinant recognized by b96.11 in the anti-idiotypic antibody, supporting an immunomodulatory role for GAD65-specific autoantibodies, as originally postulated by Jerne.

Associations between healthy eating patterns and immune function or inflammation in overweight or obese postmenopausal women.

BACKGROUND: The link between poor nutritional status and impaired immune function is well established; however, most studies have focused on individual nutrients instead of overall dietary patterns. OBJECTIVE: Our objective was to investigate associations between 3 indexes of overall diet quality [the Diet Quality Index (DQI), the DQI including supplementary calcium (DQI-Ca), and the Healthy Eating Index (HEI)] and biomarkers of inflammation and immunity. DESIGN: This cross-sectional study included 110 overweight or obese postmenopausal women. Dietary intake measured by food-frequency questionnaire was used to calculate diet quality scores. C-reactive protein (CRP) and serum amyloid A (SAA) were measured by latex-enhanced nephelometry. Flow cytometry was used to measure natural killer (NK) cell cytotoxicity and to enumerate and phenotype lymphocyte subsets. T lymphocyte proliferation was assessed by (3)H-thymidine incorporation as well as by the carboxyfluorescein-succinimidyl ester method of cell division tracking. Multivariable-adjusted linear regression analysis was used to investigate associations between diet quality scores and markers of inflammation and immune function. RESULTS: Higher diet quality was associated with increased proportions of cytotoxic and decreased proportions of helper T lymphocytes. CRP and SAA concentrations were higher among women with a lower-quality diet; these associations became nonsignificant after adjustment for body mass index or percentage body fat. We observed limited evidence for an association between healthy eating patterns and greater lymphocyte proliferation and no evidence for an association with NK cell cytotoxicity. CONCLUSION: Our results provide limited evidence that healthy eating patterns contribute to enhanced immune function and reduced inflammation in overweight and obese postmenopausal women.

Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice.

OBJECTIVE: Osteoprotegerin (OPG), a member of the tumor necrosis factor (TNF) superfamily of proteins, plays an important role in bone remodeling and is expressed in both mouse and human atherosclerotic lesions. The current study was designed to assess whether OPG plays a role in the progression and calcification of advanced atherosclerotic lesions in apoE(-/-) mice. METHODS AND RESULTS: Atherosclerotic lesion area and composition and aortic calcium content were examined in mice deficient in both OPG and apolipoprotein E (OPG(-/-).apoE(-/-) mice) at 20, 40, and 60 weeks of age. Littermate OPG(+/+).apoE(-/-) mice were used as controls. The average cross-sectional area of lesions in the innominate arteries was increased in OPG(-/-).apoE(-/-) mice at 40 and 60 weeks of age. The increase in lesion area was coupled with a reduced cellularity and an increase in connective tissue including laminated layers of elastin. Sixty-week-old OPG(-/-).apoE(-/-) mice also had an increase in the area of calcification of the lesions. There were no differences in markers of plaque stability. In vitro, OPG induced matrix metalloproteinase-9 (MMP-9) activity in macrophages and smooth muscle cells and acted as a survival factor for serum-deprived smooth muscle cells. CONCLUSIONS: OPG inhibits advanced plaque progression by preventing an increase in lesion size and lesion calcification. OPG may act as a survival factor and may modulate MMP9 production in vascular cells.

Calcification of advanced atherosclerotic lesions in the innominate arteries of ApoE-deficient mice: potential role of chondrocyte-like cells.

OBJECTIVE: Advanced atherosclerotic lesions in the innominate arteries of chow-fed apolipoprotein E-deficient mice become highly calcified with 100% frequency by 75 weeks of age. The time course, cell types, and mechanism(s) associated with calcification were investigated. METHODS AND RESULTS: The deposition of hydroxyapatite is preceded by the formation of fibro-fatty nodules that are populated by cells that morphologically resemble chondrocytes. These cells are spatially associated with small deposits of hydroxyapatite in animals between 45 and 60 weeks of age. Immunocytochemical analyses with antibodies recognizing known chondrocyte proteins show that these cells express the same proteins as chondrocytes within developing bone. Histological and electron microscopic analyses of lesions from animals between 45 and 60 weeks of age show that the chondrocyte-like cells are surrounded by dense connective tissue that stains positive for type II collagen. Nanocrystals of hydroxyapatite can be seen within matrix vesicles derived from the chondrocyte-like cells. In mice between 75 and 104 weeks of age, the lesions have significantly reduced cellularity and contain large calcium deposits. The few remaining chondrocyte-like cells are located adjacent to or within the large areas of calcification. CONCLUSIONS: Calcification of advanced lesions in chow-fed apolipoprotein E-deficient mice occurs reproducibly in mice between 45 and 75 weeks of age. The deposition of hydroxyapatite is mediated by chondrocytes, which suggests that the mechanism of calcification may in part recapitulate the process of endochondral bone formation.

Serum amyloid A and lipoprotein retention in murine models of atherosclerosis.

OBJECTIVE: Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk in humans. Because SAA associates primarily with lipoproteins in plasma and has proteoglycan binding domains, we postulated that SAA might mediate lipoprotein retention on atherosclerotic extracellular matrix. METHODS AND RESULTS: Immunohistochemistry was performed for SAA, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and perlecan on proximal aortic lesions from chow-fed low-density lipoprotein receptor (LDLR)-/- and apoE-/- mice euthanized at 10, 50, and 70 weeks. SAA was detected on atherosclerotic lesion extracellular matrix at all time points in both strains. SAA area correlated highly with lesion areas (apoE-/-, r=0.76; LDLR-/-, r=0.86), apoA-I areas (apoE-/-, r=0.88; LDLR-/-, r=0.80), apoB areas (apoE-/-, r=0.74; LDLR-/-, r=0.89), and perlecan areas (apoE-/-, r=0.83; LDLR-/-, r=0.79) (all P<0.0001). In vitro, SAA enrichment increased high-density lipoprotein (HDL) binding to heparan sulfate proteoglycans, and immunoprecipitation experiments using plasma from apoE-/- and LDLR-/- mice demonstrated that SAA was present on both apoA-I-containing and apoB-containing lipoproteins. CONCLUSIONS: In chow-fed apoE-/- and LDLR-/- mice, SAA is deposited in murine atherosclerosis at all stages of lesion development, and SAA immunoreactive area correlates highly with lesion area, apoA-I area, apoB area, and perlecan area. These findings are consistent with a possible role for SAA-mediated lipoprotein retention in atherosclerosis.

Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels.

Ca2+-binding protein-1 (CaBP1) is a Ca2+-binding protein that is closely related to calmodulin (CaM) and localized in somatodendritic regions of principal neurons throughout the brain, but how CaBP1 participates in postsynaptic Ca2+ signaling is not known. Here, we describe a novel role for CaBP1 in the regulation of Ca2+ influx through Ca(v)1.2 (L-type) Ca2+ channels. CaBP1 interacts directly with the alpha1 subunit of Ca(v)1.2 at sites that also bind CaM. CaBP1 binding to one of these sites, the IQ domain, is Ca2+ dependent and competitive with CaM binding. The physiological significance of this interaction is supported by the association of Ca(v)1.2 and CaBP1 in postsynaptic density fractions purified from rat brain. Moreover, in double-label immunofluorescence experiments, CaBP1 and Ca(v)1.2 colocalize in numerous cell bodies and dendrites of neurons, particularly in pyramidal cells in the CA3 region of the hippocampus and in the dorsal cortex. In electrophysiological recordings of cells transfected with Ca(v)1.2, CaBP1 greatly prolonged Ca2+ currents, prevented Ca2+-dependent inactivation, and caused Ca2+-dependent facilitation of currents evoked by step depolarizations and repetitive stimuli. These effects contrast with those of CaM, which promoted strong Ca2+-dependent inactivation of Ca(v)1.2 with these same voltage protocols. Our findings reveal how Ca2+-binding proteins, such as CaM and CaBP1, differentially adjust Ca2+ influx through Ca(v)1.2 channels, which may specify diverse modes of Ca2+ signaling in neurons.