bluuebunny/crossref_metadata_2025 huggingface dataset:
A Critical Review of Theory in Breast Cancer Screening Promotion across Cultures
Authors: Pasick Rena J. , Burke Nancy J.
Published: October 2007

This article reviews the contribution and potential of widely used health behavior theories in research designed to understand and redress the disproportionate burden of breast cancer borne by diverse race/ethnic, immigrant, and low-income groups associated with unequal use of mammography. We review the strengths and limitations of widely used theories and the extent to which theory contributes to the understanding of screening disparities and informs effective intervention. The dominant focus of most theories on individual cognition is critically assessed as the abstraction of behavior from its social context. Proposed alternatives emphasize multilevel ecological approaches and the use of anthropologic theory and methods for more culturally grounded understandings of screening behavior. Common and alternative treatments of fatalism exemplify this approach, and descriptive and intervention research exemplars further highlight the integration of screening behavior and sociocultural context.
Ghrelin inhibits sympathetic nervous activity in sepsis
Authors: Wu Rongqian , Zhou Mian , Das Padmalaya , Dong Weifeng , Ji Youxin , Yang Derek , Miksa Michael , Zhang Fangming , Ravikumar Thanjavur S. , Wang Ping
Published: October 2007

Our previous studies have shown that norepinephrine (NE) upregulates proinflammatory cytokines by activating α2-adrenoceptor. Therefore, modulation of the sympathetic nervous system represents a novel treatment for sepsis. We have also shown that a novel stomach-derived peptide, ghrelin, is downregulated in sepsis and that its intravenous administration decreases proinflammatory cytokines and mitigates organ injury. However, it remains unknown whether ghrelin inhibits sympathetic activity through central ghrelin receptors [i.e., growth hormone secretagogue receptor 1a (GHSR-la)] in sepsis. To study this, sepsis was induced in male rats by cecal ligation and puncture (CLP). Ghrelin was administered through intravenous or intracerebroventricular injection 30 min before CLP. Our results showed that intravenous administration of ghrelin significantly reduced the elevated NE and TNF-α levels at 2 h after CLP. NE administration partially blocked the inhibitory effect of ghrelin on TNF-α in sepsis. GHSR-la inhibition by the administration of a GHSR-la antagonist, [d-Arg1,d-Phe5, d-Trp7,9,Leu11]substance P, significantly increased both NE and TNF-α levels even in normal animals. Markedly elevated circulating levels of NE 2 h after CLP were also significantly decreased by intracerebroventricular administration of ghrelin. Ghrelin's inhibitory effect on NE release was completely blocked by intracerebroventricular injection of the GHSR-1a antagonist or a neuropeptide Y (NPY)/Y1receptor antagonist. However, ghrelin's downregulatory effect on TNF-α release was only partially diminished by these agents. Thus ghrelin has sympathoinhibitory properties that are mediated by central ghrelin receptors involving a NPY/Y1 receptor-dependent pathway. Ghrelin's inhibitory effect on TNF-α production in sepsis is partially because of its modulation of the overstimulated sympathetic nerve activation.
A computer model of gluconeogenesis and lipid metabolism in the perfused liver
Authors: Chalhoub Elie , Hanson Richard W. , Belovich Joanne M.
Published: October 2007

A mathematical model of the perfused rat liver was developed to predict intermediate metabolite concentrations and fluxes in response to changes in various substrate concentrations in the perfusion medium. The model simulates gluconeogenesis in the liver perfused separately with lactate and pyruvate and the combination of these substrates with fatty acids (oleate). The model consists of key reactions representing gluconeogenesis, glycolysis, fatty acid metabolism, tricarboxylic acid cycle, oxidative phosphorylation, and ketogenesis. Michaelis-Menten-type kinetic expressions, with control by ATP/ADP, are used for many of the reactions. For key regulated reactions (fructose-1,6-bisphosphatase, phosphofructokinase, pyruvate carboxylase, pyruvate dehydrogenase complex, and pyruvate kinase), rate expressions were developed that incorporate allosteric effectors, specific substrate relationships (e.g., cooperative binding), and/or phosphorylation/dephosphorylation using in vitro enzyme activity data and knowledge of the specific mechanisms. The model was independently validated by comparing model predictions with 10 sets of experimental data from 7 different published works, with no parameter adjustments. The simulations predict the same trends, in terms of stimulation of substrate uptake by fatty acid addition, as observed experimentally. In general, the major metabolic indicators calculated by the model are in good agreement with experimental results. For example, the simulated glucose/pyruvate mass yield is 43% compared with the average of 45% reported in the literature. The model accurately predicts the specific time constants of the glucose response (2.5–4 min) and the dynamic behavior of substrate and product fluxes. It is expected that this model will be a useful tool for analyzing the complex relationships between carbohydrate and fat metabolism.
Nonobese, insulin-deficient Ins2Akitamice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling
Authors: Hong Eun-Gyoung , Jung Dae Young , Ko Hwi Jin , Zhang Zhiyou , Ma Zhexi , Jun John Y. , Kim Jae Hyeong , Sumner Andrew D. , Vary Thomas C. , Gardner Thomas W. , Bronson Sarah K. , Kim Jason K.
Published: October 2007

Although insulin resistance has been traditionally associated with type 2 diabetes, recent evidence in humans and animal models indicates that insulin resistance may also develop in type 1 diabetes. A point mutation of insulin 2 gene in Ins2Akitamice leads to pancreatic β-cell apoptosis and hyperglycemia, and these mice are commonly used to investigate type 1 diabetes and complications. Since insulin resistance plays an important role in diabetic complications, we performed hyperinsulinemic-euglycemic clamps in awake Ins2Akitaand wild-type mice to measure insulin action and glucose metabolism in vivo. Nonobese Ins2Akitamice developed insulin resistance, as indicated by an ∼80% reduction in glucose infusion rate during clamps. Insulin resistance was due to ∼50% decreases in glucose uptake in skeletal muscle and brown adipose tissue as well as hepatic insulin action. Skeletal muscle insulin resistance was associated with a 40% reduction in total GLUT4 and a threefold increase in PKCε levels in Ins2Akitamice. Chronic phloridzin treatment lowered systemic glucose levels and normalized muscle insulin action, GLUT4 and PKCε levels in Ins2Akitamice, indicating that hyperglycemia plays a role in insulin resistance. Echocardiography showed significant cardiac remodeling with ventricular hypertrophy that was ameliorated following chronic phloridzin treatment in Ins2Akitamice. Overall, we report for the first time that nonobese, insulin-deficient Ins2Akitamice develop type 2 diabetes phenotypes including peripheral and hepatic insulin resistance and cardiac remodeling. Our findings provide important insights into the pathogenesis of metabolic abnormalities and complications affecting type 1 diabetes and lean type 2 diabetes subjects.
Greater glycogen utilization during β1- than β2-adrenergic receptor stimulation in the isolated perfused rat heart
Authors: McConville Patrick , Lakatta Edward G. , Spencer Richard G.
Published: October 2007

Differences in energy metabolism during β1- and β2-adrenergic receptor (AR) stimulation have been shown to translate to differences in the elicited functional responses. It has been suggested that differential access to glycogen during β1- compared with β2-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved13C- and31P-NMR spectroscopy was used during β1- and β2-AR stimulation at matched peak workload (2.5 times baseline) in the isolated perfused rat heart to monitor glycogen levels, phosphorylation potential, and intracellular pH. Simultaneous measurements of left ventricular (LV) function [LV developed pressure (LVDP)], heart rate (HR), and rate-pressure product (RPP = LVDP × HR) were also performed. The heart was perfused under both substrate-free (SF) conditions and with exogenous glucose (G). The greater glycogenolysis was observed during β1- than β2-AR stimulation with G (54% vs. 38% reduction, P = 0.006) and SF (92% vs. 79% reduction, P = 0.04) perfusions. The greater β1-AR-mediated glycogenolysis was correlated with greater ability to sustain the initial contractile response. However, with SF perfusion, the duration of this ability was limited: excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during β1- than β2-AR stimulation. Therefore, endogenous glycogen stores are depleted earlier and to a greater extent, despite a slightly weaker overall inotropic response, during β1- than β2-AR stimulation. These findings are consistent with β1-AR-specific PKA-dependent glycogen phosphorylase kinase signaling.
Increased TNFα and CCAAT/enhancer-binding protein homologous protein with aging predispose preadipocytes to resist adipogenesis
Authors: Tchkonia Tamara , Pirtskhalava Tamar , Thomou Thomas , Cartwright Mark J. , Wise Barton , Karagiannides Iordanes , Shpilman Alexander , Lash Timothy L. , Becherer J. David , Kirkland James L.
Published: October 2007

Fat depot sizes peak in middle age but decrease by advanced old age. This phenomenon is associated with ectopic fat deposition, decreased adipocyte size, impaired differentiation of preadipocytes into fat cells, decreased adipogenic transcription factor expression, and increased fat tissue inflammatory cytokine generation. To define the mechanisms contributing to impaired adipogenesis with aging, we examined the release of TNFα, which inhibits adipogenesis, and the expression of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), which blocks activity of adipogenic C/EBP family members, in preadipocytes cultured from young, middle-aged, and old rats. Medium conditioned by fat tissue, as well as preadipocytes, from old rats impeded lipid accumulation by preadipocytes from young animals. More TNFα was released by preadipocytes from old than young rats. Differences in TNFα-converting enzyme, TNFα degradation, or the presence of macrophages in cultures were not responsible. TNFα induced rat preadipocyte CHOP expression. CHOP was higher in undifferentiated preadipocytes from old than younger animals. Overexpression of CHOP in young rat preadipocytes inhibited lipid accumulation. TNFα short interference RNA reduced CHOP and partially restored lipid accumulation in old rat preadipocytes. CHOP normally increases during late differentiation, potentially modulating the process. This late increase in CHOP was not affected substantially by aging: CHOP was similar in differentiating preadipocytes and fat tissue from old and young animals. Hypoglycemia, which normally causes an adaptive increase in CHOP, was less effective in inducing CHOP in preadipocytes from old than younger animals. Thus increased TNFα release by undifferentiated preadipocytes with elevated basal CHOP contributes to impaired adipogenesis with aging.
Effects of lycopene on the induction of foam cell formation by modified LDL
Authors: Napolitano Mariarosaria , De Pascale Clara , Wheeler-Jones Caroline , Botham Kathleen M. , Bravo Elena
Published: October 2007

The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with lycopene in the presence or absence of native LDL (nLDL) or LDL modified by oxidation (oxLDL), aggregation (aggLDL), or acetylation (acLDL). The cholesterol content, lipid synthesis, scavenger receptor activity, and the secretion of inflammatory [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and anti-inflammatory (IL-10) cytokines was determined. Lycopene was found to decrease the synthesis of cholesterol ester in incubations without LDL or with oxLDL while triacylglycerol synthesis was reduced in the presence of oxLDL and aggLDL. Scavenger receptor activity as assessed by the uptake of acLDL was decreased by ∼30% by lycopene. In addition, lycopene inhibited IL-10 secretion by up to 74% regardless of the presence of nLDL or aggLDL but did not affect IL-1β or TNF-α release. Lycopene also reduced the relative abundance of mRNA transcripts for scavenger receptor A (SR-A) in THP-1 macrophages treated with aggLDL. These findings suggest that lycopene may reduce macrophage foam cell formation induced by modified LDL by decreasing lipid synthesis and downregulating the activity and expression of SR-A. However, these effects are accompanied by impaired secretion of the anti-inflammatory cytokine IL-10, suggesting that lycopene may also exert a concomitant proinflammatory effect.
Induction of endoplasmic reticulum stress-induced β-cell apoptosis and accumulation of polyubiquitinated proteins by human islet amyloid polypeptide
Authors: Huang Chang-jiang , Haataja Leena , Gurlo Tatyana , Butler Alexandra E. , Wu Xiuju , Soeller Walter C. , Butler Peter C.
Published: October 2007

The islet in type 2 diabetes is characterized by an ∼60% β-cell deficit, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (hIAPP) but not rodent IAPP (rIAPP) forms toxic oligomers and amyloid fibrils in an aqueous environment. We previously reported that overexpression of hIAPP in transgenic rats triggered endoplasmic reticulum (ER) stress-induced apoptosis in β-cells. In the present study, we sought to establish whether the cytotoxic effects of hIAPP depend on its propensity to oligomerize, rather than as a consequence of protein overexpression. To accomplish this, we established a novel homozygous mouse model overexpressing rIAPP at a comparable expression rate and, on the same background, as a homozygous transgenic hIAPP mouse model previously reported to develop diabetes associated with β-cell loss. We report that by 10 wk of age hIAPP mice develop diabetes with a deficit in β-cell mass due to increased β-cell apoptosis. The rIAPP transgenic mice counterparts do not develop diabetes or have decreased β-cell mass. Both rIAPP and hIAPP transgenic mice have increased expression of BiP, but only hIAPP transgenic mice have elevated ER stress markers (X-box-binding protein-1, nuclear localized CCAAT/enhancer binding-protein homologous protein, active caspase-12, and accumulation of ubiquitinated proteins). These findings indicate that the β-cell toxic effects of hIAPP depend on the propensity of IAPP to aggregate, but not on the consequence of protein overexpression.
Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats
Authors: Obrosova Irina G. , Drel Viktor R. , Oltman Christine L. , Mashtalir Nazar , Tibrewala Jyoti , Groves John T. , Yorek Mark A.
Published: October 2007

Evidence for important roles of the highly reactive oxidant peroxynitrite in diabetic complications is emerging. We evaluated the role of peroxynitrite in early peripheral neuropathy and vascular dysfunction in STZ-diabetic rats. In the first dose-finding study, control and STZ-diabetic rats were maintained with or without the potent peroxynitrite decomposition catalyst Fe(III)tetrakis-2-( N-triethylene glycol monomethyl ether) pyridyl porphyrin (FP15) at 3, 5, or 10 mg·kg−1·day−1in the drinking water for 4 wk after an initial 2 wk without treatment for assessment of early neuropathy. In the second study with similar experimental design, control and STZ-diabetic rats were maintained with or without FP15, 5 mg·kg−1·day−1, for vascular studies. Rats with 6-wk duration of diabetes developed motor and sensory nerve conduction velocity deficits, mechanical hyperalgesia, and tactile allodynia in the absence of small sensory nerve fiber degeneration. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in the sciatic nerve and dorsal root ganglia. All these variables were dose-dependently corrected by FP15, with minimal differences between the 5 and 10 mg·kg−1·day−1doses. FP15, 5 mg·kg−1·day−1, also corrected endoneurial nutritive blood flow and nitrotyrosine, but not superoxide, fluorescence in aorta and epineurial arterioles. Diabetes-induced decreases in acetylcholine-mediated relaxation by epineurial arterioles and coronary and mesenteric arteries, as well as bradykinin-induced relaxation by coronary and mesenteric arteries, were alleviated by FP15 treatment. The findings reveal the important role of nitrosative stress in early neuropathy and vasculopathy and provide the rationale for further studies of peroxynitrite decomposition catalysts in long-term diabetic models.
Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiogensin-converting enzyme inhibition
Authors: Clerk Lucy H. , Vincent Michelle A. , Barrett Eugene J. , Lankford Miles F. , Lindner Jonathan R.
Published: October 2007

Acute physiological hyperinsulinemia increases skeletal muscle capillary blood volume (CBV), presumably to augment glucose and insulin delivery. We hypothesized that insulin-mediated changes in CBV are impaired in type 2 diabetes mellitus (DM) and are improved by angiotensin-converting enzyme inhibition (ACE-I). Zucker obese diabetic rats (ZDF, n = 18) and control rats ( n = 9) were studied at 20 wk of age. One-half of the ZDF rats were treated with quinapril (ZDF-Q) for 15 wk prior to study. CBV and capillary flow in hindlimb skeletal muscle were measured by contrast-enhanced ultrasound (CEU) at baseline and at 30 and 120 min after initiation of a euglycemic hyperinsulinemic clamp (3 mU·min−1·kg−1). At baseline, ZDF and ZDF-Q rats were hyperglycemic and hyperinsulinemic vs. controls. Glucose utilization in ZDF rats was 60–70% lower ( P < 0.05) than in controls after 30 and 120 min of hyperinsulinemia. In ZDF-Q rats, glucose utilization was impaired at 30 min but similar to controls at 120 min. Basal CBV was lower in ZDF and ZDF-Q rats compared with controls (13 ± 4, 7 ± 3, and 9 ± 2 U, respectively). With hyperinsulinemia, CBV increased by about twofold in control animals at 30 and 120 min, did not change in ZDF animals, and increased in ZDF-Q animals only at 120 min to a level similar to controls. Anatomic capillary density on immunohistology was not different between groups. We conclude that insulin-mediated capillary recruitment in skeletal muscle, which participates in glucose utilization, is impaired in animals with DM and can be partially reversed by chronic ACE-I therapy.
Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity
Authors: Roberge Claude , Carpentier André C. , Langlois Marie-France , Baillargeon Jean-Patrice , Ardilouze Jean-Luc , Maheux Pierre , Gallo-Payet Nicole
Published: October 2007

The aim of this review is to explore the dysregulation of adrenocortical secretions as a major contributor in the development of obesity and insulin resistance. Disturbance of adipose tissue physiology is one of the primary events in the development of pathologies associated with the metabolic syndrome, such as obesity and type 2 diabetes. Several studies indicate that alterations in metabolism of glucocorticoids (GC) and androgens, as well as aldosterone in excess, are involved in the emergence of metabolic syndrome. Cross talk among adipose tissue, the hypothalamo-pituitary complex, and adrenal gland activity plays a major role in the control of food intake, glucose metabolism, lipid storage, and energy balance. Perturbation of this cross talk induces alterations in the regulatory mechanisms of adrenocortical steroid synthesis, secretion, degradation, and/or recycling, at the level of the zonae glomerulosa (aldosterone), fasciculata (GC and GC metabolites), and reticularis (androgens and androgen precursors DHEA and DHEAS). As a whole, these adrenocortical perturbations contribute to the development of metabolic syndrome at both the paracrine and systemic level by favoring the physiological dysregulation of organs responsive to aldosterone, GC, and/or androgens, including adipose tissue.
Common and specific effects of the two major forms of prolactin in the rat testis
Authors: Williams Valencia L. , DeGuzman Ariel , Dang Hong , Kawaminami Mitsumori , Ho Timothy W. C. , Carter David G. , Walker Ameae M.
Published: October 2007

Prolactin (PRL) has both stimulatory and inhibitory effects on testicular function, a finding we hypothesized may be related in some part to the form of the hormone present or administered. In the analysis of the pituitary secretion profiles of early pubescent vs. mature male rats, we found PRL released from early pubescent pituitaries had about twice the degree of phosphorylation. Treatment of mature males with either unmodified PRL (U-PRL) or phosphorylated PRL (via the molecular mimic S179D PRL) for a period of 4 wk (circulating level of ∼50 ng/ml) showed serum testosterone decreased by ∼35% only by treatment with the phospho-mimic S179D PRL. Given the specificity of this effect, it was initially surprising that both forms of PRL decreased testicular expression of 3β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein. Both forms also increased expression of the luteinizing hormone receptor, but only S179D PRL increased the ratio of short to long PRL receptors. Endogenous PRL and luteinizing hormone levels were unchanged in all groups in this time frame, suggesting that effects on steroidogenic gene expression were directly on the testis. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling analysis combined with staining for 3β-hydroxysteroid dehydrogenase and morphometric analysis showed that S179D PRL, but not U-PRL, increased apoptosis of Leydig cells, a finding supported by increased staining for Fas and Fas ligand in the testicular interstitium, providing an explanation for the specific effect on testosterone. S179D PRL, but not U-PRL, also increased apoptosis of primary spermatogonia, and U-PRL, but not S179D PRL, decreased apoptosis of elongating spermatids. Thus, in mature males, hyperprolactinemic levels of both forms of PRL have common effects on steroidogenic proteins, but specific effects on the apoptosis of Leydig and germ cells.
Baroreflexes of the rat. V. Tetanus-induced potentiation of ADN A-fiber responses at the NTS
Authors: Tang Xiaorui , Dworkin Barry R.
Published: October 2007

In a long-term neuromuscular blocked (NMB) rat preparation, tetanic stimulation of the aortic depressor nerve (ADN) enhanced the A-fiber evoked responses (ERs) in the cardiovascular region, the nucleus of the solitary tract (dmNTS). The potentiation persisted for at least several hours and may be a mechanism for adaptive adjustment of the gain of the baroreflex, with functional implications for blood pressure regulation. Using a capacitance electrode, we selectively stimulated A-fibers and acquired a stable 10-h “A-fiber only” ER baseline at the dmNTS. Following baseline, an A+C-fiber activating tetanus was applied to the ADN. The tetanus consisted of 1,000 “high current” pulses (10 trains; 300 μs, 100 Hz, 1 s), with intertrain interval of 9 s. A 10-h A-fiber only posttetanic test phase repeated the stimulus pattern of the baseline. Fourteen tetanus experiments were done in 12 rats. Compared with the baseline before tetanus, the A-fiber ER magnitudes of posttetanus hours were larger [ F(13, 247) = 3.407, P < .001]; additionally, the 10-h posttetanus magnitude slopes were more positive than during 10 h before tetanus (df = 13; t = −3.47; P < 0.005); thus, an ADN A+C fiber-activating tetanus produced increases in the magnitude of the A-fiber ERs in the dmNTS that persisted for several hours. In an additional rat, application of an NMDA receptor antagonist, prior to the tetanus, blocked the potentiation effect. The stimulus protocols, magnitude and duration of the effect, and pharmacology resemble associative long-term potentiation (LTP).
Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion
Authors: Ge Yuqiang , Strait Kevin A. , Stricklett Peter K. , Yang Tianxin , Kohan Donald E.
Published: October 2007

Collecting duct (CD)-derived endothelin-1 (ET-1) exerts natriuretic, diuretic, and hypotensive effects. In vitro studies have implicated cyclooxygenase (COX) metabolites, and particularly PGE2, as important mediators of CD ET-1 effects. However, it is unknown whether PGE2 mediates CD-derived ET-1 actions in vivo. To test this, CD ET-1 knockout (KO) and control mice were studied. During normal salt and water intake, urinary PGE2 excretion was unexpectedly increased in CD ET-1 KO mice compared with controls. Salt loading markedly increased urinary PGE2 excretion in both groups of mice; however, the levels remained relatively higher in KO animals. Acutely isolated inner medullary collecting duct (IMCD) from KO mice also had increased PGE2 production. The increased IMCD PGE2 was COX-2 dependent, since NS-398 blocked all PGE2 production. However, increased CD ET-1 KO COX-2 protein or mRNA could not be detected in inner medulla or IMCD, respectively. Inner medullary COX-1 mRNA and protein levels and IMCD COX-1 mRNA levels were unaffected by Na intake or CD ET-1 KO. KO mice on a normal or high-Na diet had elevated blood pressure compared with controls; this difference was not altered by indomethacin or NS-398 treatment. However, indomethacin or NS-398 did increase urine osmolality and reduce urine volume in KO, but not control, animals. In summary, IMCD COX-2-dependent PGE2 production is increased in CD ET-1 KO mice, indicating that CD-derived ET-1 is not a primary regulator of IMCD PGE2. Furthermore, the increased PGE2 in CD ET-1 KO mice partly compensates for loss of ET-1 with respect to maintaining urinary water excretion, but not in blood pressure control.
Hedonic-Specific Activity in Piriform Cortex During Odor Imagery Mimics That During Odor Perception
Authors: Bensafi Moustafa , Sobel Noam , Khan Rehan M.
Published: October 2007

Although it is known that visual imagery is accompanied by activity in visual cortical areas, including primary visual cortex, whether olfactory imagery exists remains controversial. Here we asked whether cue-dependent olfactory imagery was similarly accompanied by activity in olfactory cortex, and in particular whether hedonic-specific patterns of activity evident in olfactory perception would also be present during olfactory imagery. We used functional magnetic resonance imaging to measure activity in subjects who alternated between smelling and imagining pleasant and unpleasant odors. Activity induced by imagining odors mimicked that induced by perceiving real odorants, not only in the particular brain regions activated, but also in its hedonic-specific pattern. For both real and imagined odors, unpleasant stimuli induced greater activity than pleasant stimuli in the left frontal portion of piriform cortex and left insula. These findings combine with findings from other modalities to suggest activation of primary sensory cortical structures during mental imagery of sensory events.
Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons
Authors: Zhang Hai Xia , Thio Liu Lin
Published: October 2007

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.
Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice
Authors: Inoue Masashi , Glendinning John I. , Theodorides Maria L. , Harkness Sarah , Li Xia , Bosak Natalia , Beauchamp Gary K. , Bachmanov Alexander A.
Published: October 2007

The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6- Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (d-tryptophan, d-phenylalanine, l-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (l-glutamine, l-threonine, l-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5′-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system.
Alternative promoter usage and alternative splicing contribute to mRNA heterogeneity of mouse monocarboxylate transporter 2
Authors: Zhang Shelley X. L. , Searcy Tina R. , Wu Yiman , Gozal David , Wang Yang
Published: October 2007

Expression patterns of monocarboxylate transporter 2 (MCT2) display mRNA diversity in a tissue-specific fashion. We cloned and characterized multiple mct2 5′-cDNA ends from the mouse and determined the structural organization of the mct2 gene. We found that transcription of this gene was initiated from five independent genomic regions that spanned >80 kb on chromosome 10, resulting in five unique exon 1 variants (exons 1a, 1b, 1c, 1d, and 1e) that were then spliced to the common exon 2. Alternative splicing of four internal exons (exons AS1, AS2, AS3, and exon 3) greatly increased the complexity of mRNA diversity. While exon 1c was relatively commonly used for transcription initiation in various tissues, other exon 1 variants were used in a tissue-specific fashion, especially exons 1b and 1d that were used exclusively for testis-specific expression. Sequence analysis of 5′-flanking regions upstream of exons 1a, 1b, and 1c revealed the presence of numerous potential binding sites for ubiquitous transcription factors in all three regions and for transcription factors implicated in testis-specific or hypoxia-induced gene expression in the 1b region. Transient transfection assays demonstrated that each of the three regions contained a functional promoter and that the in vitro, cell type-specific activities of these promoters were consistent with the tissue-specific expression pattern of the mct2 gene in vivo. These results indicate that tissue-specific expression of the mct2 gene is controlled by multiple alternative promoters and that both alternative promoter usage and alternative splicing contribute to the remarkable mRNA diversity of the gene.
Black Canadian Studies as the Cutting Edge of Change
Authors: Barnstead John A.
Published: October 2007

Far removed though Black Canadian studies might initially appear from the often self-centered, inward-looking, and marginalized area of Russian studies, as head of Dalhousie University's Department of Russian Studies, the author has experienced the direct impact of Black Canadian studies on teaching, research, and curriculum development. Indeed, the 1996 establishment of the James Robinson Johnston Chair in Black Canadian Studies at Dalhousie University, with its national mandate for reifying the idea of Black studies within the Canadian academy, generated a series of far-ranging and innovative challenges that led to a critical reexamination of the central figure of Russian literature Aleksandr Sergeevich Pushkin. Black studies invigorates through reflective retrospection and critical introspection, both transforming outlooks and inspiring the scholarly search for Truth. In the author's opinion, the task of Black studies in Canada remains that of opening eyes, minds, and hearts.
Self-Control as an Executive Function
Authors: Beaver Kevin M. , Wright John Paul , Delisi Matt
Published: October 2007

According to Gottfredson and Hirschi (1990), levels of self-control are determined by parental management techniques, not by biological and genetic influences. Recent behavioral genetic and neuroscientific research challenges this view and reveals that biogenic factors are largely responsible for the development of self-control. The current article builds off this body of literature and argues that Gottfredson and Hirschi's parental socialization thesis should be reformulated to recognize that self-control is just one part of a larger constellation of executive functions that are modulated by the prefrontal cortex of the brain. Using a sample of about 3,000 children, this reformulated thesis was tested by examining whether neuropsychological deficits are predictive of parental and teacher reports of the child's level of self-control. Results revealed that measures of neuropsychological deficits were associated with variability in childhood self-control. Theoretical implications of the findings are discussed.
Risk of Suicide in Juvenile Justice Facilities
Authors: Gallagher Catherine A. , Dobrin Adam
Published: October 2007

Two recent publications have reported vastly different rates of suicide in juvenile-justice residential facilities using the same data. Similarly, divergent rates were calculated on juvenile suicides while in custody using the same data in the 1980s. Using data from the Juvenile Residential Facility Census and the Census of Juveniles in Residential Placement, this article demonstrates the underlying differences in the suicide rate calculations by drawing on the historical and epidemiological literature. It highlights the arithmetical relationships between the rates and suggests which methods are best depending on the purpose of the exercise. Facility administrators may find beds-based rates more meaningful for comparisons on rates of suicide across facilities, whereas mental health professionals may prefer person-based rates to describe the risk of suicide in the juvenile justice population.
A Structural Examination of the Predictors of Sexual Coercion Against Children in Adolescent Sexual Offenders
Authors: Daversa Maria T. , Knight Raymond A.
Published: October 2007

The study proposed an etiological model for sexually offending behavior against younger victims. In a sample of adolescent sexual offenders ( N = 329), it tested whether attachment disruptions, specific maltreatment experiences, or combinations of early abuse experiences played a role in the development of certain unique, core personality traits (i.e., sexual inadequacy, psychopathy, child sexual arousal) that mediate the prediction of sexually coercive behavior. Juvenile sexual offenders were administered the Multidimensional Assessment of Sex and Aggression. In a structural equation model, four significant paths and one minimal path emerged that predicted the preference for younger victims. The model supports the contributory role of emotional abuse (i.e., neglect and antipathy) to the development of the latent variable psychopathy analysis inadequacies and suggests unique features in a subgroup of adolescent child molesters. Thus, this model provides data for the preliminary design of a dimensional model of adolescent sexual coercion against younger children.
Explaining Police Bias
Authors: Smith Michael R. , Alpert Geoffrey P.
Published: October 2007

Although recent empirical research has shown that Blacks and Hispanics are consistently overrepresented among police stops, searches, and arrests, few criminologists have attempted to provide a theoretical explanation for the disparities reported in the research literature. This article proposes a theory of individual police behavior that is grounded in social— psychological research on stereotype formation and that assumes a nonmotivational but biased response to minority citizens by the police. Accordingly, stereotype formation and its consequences are largely unintentional and are driven by social conditioning and the illusory correlation phenomenon, which results in the overestimation of negative behaviors associated with minority group members. After specifying the theory, the article presents a research agenda for empirically testing and verifying its propositions.
Psychiatric Symptoms and Substance Use Among Juvenile Offenders
Authors: Vaughn Michael G. , Freedenthal Stacey , Jenson Jeffrey M. , Howard Matthew O.
Published: October 2007

The high rate of co-occurring mental health and substance abuse problems among antisocial and delinquent youth is a widely recognized problem in the juvenile justice system. Yet few studies have delineated meaningful clinical distinctions in the characteristics of offenders with co-occurring problems. Latent profile analysis was used to identify subgroups of juvenile offenders based on clinically relevant measures of psychiatric symptoms (including past traumatic experiences), lifetime substance use, and drug- and alcohol-related problems stemming from the use of psychoactive substances in a statewide population ( n = 723). Findings revealed that a four-class solution fit the data optimally. The four classes identified represented a severity-based gradient of symptom and substance use endorsement ranging from a mild subgroup ( n = 195; 27.0%), to moderately low ( n = 250; 34.6%) and high ( n = 197; 27.2%) subgroups, and finally, a severely distressed subgroup ( n = 81; 11.2%). Implications for identifying and treating young offenders with co-occurring mental health and substance abuse problems are noted.
The Effects of Prenatal Problems, Family Functioning, and Neighborhood Disadvantage in Predicting Life-Course-Persistent Offending
Authors: Turner Michael G. , Hartman Jennifer L. , Bishop Donna M.
Published: October 2007

Research examining Moffitt's dual taxonomy theory of offending has generally supported the idea that neuropsychological deficits interact with disadvantaged familial environments to predict life-course-persistent offending. Most research, however, has neglected to investigate the power of this interaction across different neighborhood and racial contexts. Using data extracted from the National Longitudinal Survey of Youth, Moffitt's biosocial hypothesis is tested across different neighborhood and racial contexts. The findings indicate that the biosocial interaction predicts life-course-persistent offending only among non-Whites in disadvantaged neighborhoods. Stated differently, macro-level structural factors appear to moderate the effects of individual and family risks. That poor non-Whites reside in neighborhoods that are ecologically distinct from those in which poor Whites reside exacerbates the criminogenic effects of individual-level deficits and family disadvantage.
The Military's Corporate Interests
Authors: Lee Terence
Published: October 2007

In “Civil–Military Relations in Indonesia and the Philippines,” Mark Beeson argued that the likelihood of future military interventions in Indonesia and the Philippines was best understood by examining the countries' political economies. Beeson contended that because the Indonesian military remains heavily involved in economic activities, it will likely remain politically quiescent. And because fewer opportunities exist for the Philippine military to engage in business undertakings, the specter of further military interventions remains. Beeson's argument is characteristic of the corporate interest perspective in the civil-military relations literature. This article examines the effectiveness of corporate interest arguments in explaining military interventions into the political arena. It advances two main arguments: first, corporate interest propositions are under-specified and not analytically useful to explain military interventions. Second, by concentrating on the corporate interests of the Indonesian and Philippine militaries, Beeson omitted more salient factors that have led to prior interventions in the two countries.
Reducing the risk of becoming a victim of terrorism while on international business assignments
Authors: Elango B. , Graf Lee A. , Hemmasi Masoud
Published: October 2007

This article presents an experiential exercise on how a businessperson, engaged in foreign travel, can decrease the risk of becoming an easy victim of terrorism or crime. This exercise provides an introduction to those unfamiliar with international travel security issues to identify the vulnerabilities that could be exploited by terrorists and, then, to develop a plan to diminish such threats. A quiz and expert answers are included as part of the exercise to bolster participants' depth of analysis and their understanding of how to avoid becoming a victim of a terrorist act.
The Theory of the Sick Breast Lobe and the Possible Consequences
Authors: Tot Tibor
Published: October 2007

We hypothesize that carcinoma in situ, and consequently breast carcinoma in general, is a lobar disease because the simultaneously or asynchronously appearing, often multiple tumor foci develop within a single lobe. The sick lobe carries some kind of genetic instability already from its initialization during the early embryonic life and is more sensitive to noxious influences than the other lobes within the same breast. Decades of postnatal life with accumulation of additional genetic alterations are needed for malignant transformation of the cells within the sick lobe. The transformation is often multifocal (involving separate distant lobules of this lobe) or diffuse (involving the larger ducts). This hypothesis offers new perspectives in cancer prevention, because selective visualization, excision, or destruction of the sick lobe before development of malignant lesions would substantially reduce the incidence of breast carcinoma.
Synchronous Gastric Gastrointestinal Stromal Tumor and Signet-Ring Cell Adenocarcinoma: A Case Report
Authors: Lee Fang-Yi , Jan Yee-Jee , Wang John , Yu Cheng-Chan , Wu Cheng-Chung
Published: October 2007

Synchronous tumors of the stomach are uncommon. We present a unique case of gastric synchronous tumors composed of signet-ring cell adenocarcinoma and gastrointestinal stromal tumor (GIST). The two tumors arose at the same site and were sharply juxtaposed without intermingling of morphologically distinct elements. Coincidence probably accounts for this occurrence, even if a common carcinogenic agent had been hypothesized. Preoperative imaging and endoscopic biopsy could lead to the suspicion of synchronous tumors, and an accurate histological identification of both tumors could be achieved by multiple deep endoscopic biopsies. The presence in our case of diffuse carcinomatosis indicates that the signet-ring cell adenocarcinoma had a greater adverse effect on the prognosis than the GIST.
Multiple Lymphomatous Diverticulosis and Comorbid Chronic Lymphocytic Leukemia: Novel Manifestations of Ileocolic Mantle Cell Lymphoma
Authors: Medlicott Shaun A. C. , Brown Holly A. , Roland Birgitte , Beck Paul L. , Auer Iwona , Mansoor Adnan
Published: October 2007

Mantle cell lymphoma (MCL) has tropism for the gastrointestinal tract (GIT) identifiable as multiple polyps and mass lesions throughout the GIT. We describe 2 novel manifestations of MCL. A 60-year-old woman with known chronic lymphocytic leukemia (CLL) had an exophytic mass of the appendiceal orifice. Multiple polypoid masses of the distal ileum were identified in the right hemicolectomy specimen (multiple lymphomatous polyposis). Ancillary studies confirmed the coexistence of the 2 independent lymphoproliferative disorders. A 69-year-old man had recurrent urinary tract infections and pneumatouria caused by a colovesicular fistula complicating diverticulosis coli. Segmental resections of the sigmoid and ileocecum confirmed diverticulosis of the left and right colon. Histology identified infiltrates of MCL confined to the penetrating aspects of colonic diverticula. MCL has not been documented to coexist with CLL. An invaginating morphology of lymphoma, multiple lymphomatous diverticulosis is also a novel presentation. These 2 scenarios expand MCL's known manifestations within the GIT.
Primary Synovial Sarcoma of the Kidney With Rhabdoid Features
Authors: Paláu L Mauricio A. , Thu Pham Tina , Barnard Nicola , Merino Maria J.
Published: October 2007

Synovial sarcoma is a soft tissue sarcoma with clearly defined histologic, immunophenotypic, and molecular features. It occurs predominantly in the extremities of young adults but has been reported in many other anatomic sites. Histologically, it is classified as biphasic, monophasic, and poorly differentiated. The latter category, which includes tumors with a rhabdoid morphology, has been associated with a more aggressive behavior. Generally, the biphasic variant does not pose any diagnostic problem because of its typical histologic appearance; in contrast, the monophasic and poorly differentiated variants may represent a diagnostic challenge because their microscopic features can be confused with those of other spindle cell tumors with rhabdoid features. The application of molecular techniques, such as reverse transcriptase polymerase chain reaction to detect the fusion transcript associated with the characteristic t(X;18) translocation of synovial sarcoma, has enabled the confirmation of this diagnosis, even in cases of unusual localization, such as the one we present here.