bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender‐Related Differences in the Tensile Strength of Abdominal Aortic Aneurysm
Authors: VANDE GEEST JONATHAN P. , DILLAVOU ELLEN D. , DI MARTINO ELENA S. , OBERDIER MATT , BOHRA AJAY , MAKAROUN MICHEL S. , VORP DAVID A.
Published: December 2006

Abstract:  A recent study investigated the association of gender with the growth rate of AAAs and found a significant increase in the growth rate of AAAs in women than in men. On the basis of these observations, we hypothesize that there are gender‐associated differences in AAA wall integrity and mechanical strength. The purpose of this study was to explore this hypothesis by comparing the tensile strength of freshly resected AAA tissue specimens between women and men. Seventy‐six rectangular specimens (20 mm long × 5 mm wide) from 34 patients (24 male, 10 female) were excised from the anterior wall of patients undergoing open repair of their abdominal aortic aneurysm and tested in a uniaxial tensile tester. Ultimate tensile strength (UTS) was taken as the peak stress obtained before specimen failure. While there were no statistical differences in strength between specimens taken from male and female patients, there was a trend toward a decrease in strength in females as compared to males (87.6 ± 6.7 N/cm2 vs. 67.6 ± 8.1 N/cm2, p = 0.09). To the authors knowledge this work represents the first report of differences in biomechanical properties as a function of gender. The nearly significant decrease in UTS in women versus men reported here may be important in assessing the risk of rupture in AAA. Further testing is warranted to confirm the current trends.
Vicarious Retribution: The Role of Collective Blame in Intergroup Aggression
Authors: Lickel Brian , Miller Norman , Stenstrom Douglas M. , Denson Thomas F. , Schmader Toni
Published: January 2007

We provide a new framework for understanding 1 aspect of aggressive conflict between groups, which we refer to as vicarious retribution. Vicarious retribution occurs when a member of a group commits an act of aggression toward the members of an outgroup for an assault or provocation that had no personal consequences for him or her but which did harm afellow ingroup member. Furthermore, retribution is often directed at outgroup members who, themselves, were not the direct causal agents in the original attack against the person's ingroup. Thus, retribution is vicarious in that neither the agent of retaliation nor the target of retribution were directly involved in the original event that precipitated the intergroup conflict. We describe how ingroup identification, outgroup entitativity, and other variables, such as group power, influence vicarious retribution. We conclude by considering a variety of conflict reduction strategies in light of this new theoretical framework.
Phytochemicals from Phyllanthus niruri Linn. and their pharmacological properties: a review
Authors: Bagalkotkar G , Sagineedu S R , Saad M S , Stanslas J
Published: December 2006

This review discusses the medicinal plant Phyllanthus niruri Linn. (Euphorbiaceae), its wide variety of phytochemicals and their pharmacological properties. The active phytochemicals, flavonoids, alkaloids, terpenoids, lignans, polyphenols, tannins, coumarins and saponins, have been identified from various parts of P. niruri. Extracts of this herb have been proven to have therapeutic effects in many clinical studies. Some of the most intriguing therapeutic properties include anti-hepatotoxic, anti-lithic, anti-hypertensive, anti-HIV and anti-hepatitis B. Therefore, studies relating to chemical characteristics and structural properties of the bioactive phytochemicals found in P. niruri are very useful for further research on this plant as many of the phytochemicals have shown preclinical therapeutic efficacies for a wide range of human diseases, including HIV/AIDS and hepatitis B.
Ageing to arrhythmias: conundrums of connections in the ageing heart
Authors: Jones Sandra A
Published: December 2006

The proportion of the population that is elderly continues to increase, leading to an increasing need to address problems chiefly associated with old age. Progressive ageing of the heart is associated with an increasing incidence of arrhythmias and disorders of the normal origin of the heartbeat, the sinoatrial node. This intrinsic pacemaker of the heart has an increasing tendency with age to lose its dominant role in pacing the heart, and regulation of heart rate becomes erratic. This ‘sick sinus syndrome’ is associated with fainting, palpitations, shortness of breath and sudden death. Current treatment of this condition is by implantation of an artificial pacemaker, an intervention increasingly required with age. The current evidence suggests that the normal heartbeat fails due to changes in the expression of critical proteins that ensure the correct production and conduction of the cardiac action potential. Depletion of a protein directly responsible for providing electrical connections between the cells of the heart, connexin 43, appears to leave the normal cardiac pacemaker disconnected and unable to drive the heart. This process may be associated with age-dependent changes in stress-related signalling. Simple interventions such as exercise could impact on the processes hypothesized to be involved and may offer a means to preserve the stability of the electrical activity of the heart into old age without pharmacological manipulation.
Pectin-cysteine conjugate: synthesis and in-vitro evaluation of its potential for drug delivery
Authors: Majzoob Sayeh , Atyabi Fatemeh , Dorkoosh Farid , Kafedjiiski Krum , Loretz Brigitta , Bernkop-Schnürch Andreas
Published: December 2006

This study was aimed at improving certain properties of pectin by introduction of thiol moieties on the polymer. Thiolated pectin was synthesized by covalent attachment of cysteine. Pectin-cysteine conjugate was evaluated for its ability to be degraded by pectinolytic enzyme. The toxicity profile of the thiolated polymer in Caco-2-cells, its permeation enhancing effect and its mucoadhesive and swelling properties were studied. Moreover insulin-loaded hydrogel beads of the new polymer were examined for their stability in simulated gastrointestinal conditions and their drug release profile. The new polymer displayed 892.27 ± 68.68 μmol thiol groups immobilized per g polymer, and proved to have retained its biodegradability, upon addition of Pectinex Ultra SPL in-vitro, determined by viscosity measurements and titration method. Pectin-cysteine showed no severe toxicity in Caco-2 cells, as tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Moreover, the synthesized polymer exhibited a relative permeation enhancement ratio of 1.61 for sodium fluorescein, compared to unmodified pectin. Pectin-cysteine conjugate exhibited approximately 5-fold increased in in-vitro adhesion duration and significantly improved cohesive properties. Zinc pectin-cysteine beads showed improved stability in simulated gastrointestinal media; however, insulin release from these beads followed the same profile as unmodified zinc pectinate beads. Due to favourable safety and biodegradability profile, and improved cohesive and permeation-enhancing properties, pectin-cysteine might be a promising excipient in various transmucosal drug delivery systems.
Optimization of tamsulosin hydrochloride controlled release pellets coated with Surelease and neutralized HPMCP
Authors: Kim Min-Soo , Kim Jeong-Soo , Lee Sibeum , Jun Seoung Wook , Park Jeong-Sook , Woo Jong-Soo , Hwang Sung-Joo
Published: December 2006

This study was to optimize the coating level in the development of controlled release pellets coated with Surelease and neutralized hydroxypropyl methylcellulose phthalate (HPMCP) by a computer optimization technique based on a response surface methodology utilizing polynomial equation. A full factorial 32 design was used for the optimization procedure with coating level (X1) and HPMCP content (X2) as the independent variables. The drug release percent at 2, 3 and 5 h were the target responses, which were restricted to 12–39% (Y1), 44–70% (Y2) and 70–100% (Y3), respectively. The quadratic model was well fitted to the data, and the resulting equation was used to predict the responses in the optimal region. It was shown that the optimized coating formulation was achieved at the ratio of 3:1 (Surelease: neutralized HPMCP) with 20% coating level. The optimized formulation showed release profiles and responses, which were close to predicted responses. Therefore, a full factorial 32 design and optimization technique can be successfully used in the development of optimized coating formulations based on Surelease and neutralized HPMCP to achieve a controlled release drug delivery system containing tamsulosin hydrochloride.
Blockade of scavenger receptor class B type I raises high density lipoprotein cholesterol levels but exacerbates atherosclerotic lesion formation in apolipoprotein E deficient mice
Authors: Kitayama Ken , Nishizawa Tomohiro , Abe Koji , Wakabayashi Kenji , Oda Tomiichiro , Inaba Toshimori , Amemiya Yoshiya
Published: December 2006

Recent accumulating evidence supports the concept that raising high-density lipoprotein (HDL) may represent an additional therapeutic target for prevention of cardiovascular disease. Scavenger receptor class B type I plays a critical role in plasma HDL cholesterol concentration and structure. This study investigated the effect of scavenger receptor class B type I blockade by a synthetic scavenger receptor class B type I blocker on plasma lipids and atherosclerosis lesion formation in apolipoprotein E (apoE)-deficient mice. N-[4-(4-tert-Butoxycarbonylpiperazin-1-yl)phenyl]-(2-chloro-5-nitrophenyl)carboxamide (R-138329), a novel scavenger receptor class B type I blocker, was identified by screening with a half-maximal inhibitory potency (IC50 value) of around 1 μM in scavenger receptor class B type I-expressing COS-1 cells. Male apoE-deficient mice were fed a chow diet with or without R-138329 (0.01-0.10%, approximately 10–100 mg kg−1, n = 9 or 10) for 12 weeks. Compared with control, treatment with R-138329 at 0.10% caused significant (P < 0.05) increases in plasma HDL cholesterol levels, and decreases in non-HDL cholesterol and triglyceride levels. Furthermore, R-138329 at 0.01% significantly increased the extent of atherosclerotic lesion formation in the aorta by 98% (P < 0.05), while favourable changes in plasma lipid parameters were achieved. The results of quantitative analysis of atherosclerosis lesion areas were: control, 102691 ±22871 μm2 (n = 10); R-138329 0.01%, 119792 ± 30842 μm2 (n = 9); R-138329 0.03%, 141346 ± 21934 μm2 (n = 10); and R-138329 0.10% 203732 ± 36326 μm2 (n = 10). To clarify the mechanistic basis underlying this preferential deterioration, we examined the potential impact on closely related cellular functions. Further studies revealed that the active metabolite of R-138329 inhibited scavenger receptor class B type I-mediated cholesterol efflux. This study demonstrates for the first time pharmacological blockade of scavenger receptor class B type I in apoE-deficient mice. Blockade of scavenger receptor class B type I deteriorates atherosclerotic lesion formation in apoE-deficient mice even though it favourably affects plasma lipid parameters such as raising HDL cholesterol and decreasing non-HDL cholesterol. These results provide new insights for pharmaceutical industry research and development issues.
Changes in hepatic gene expression associated with the hypocholesterolaemic activity of royal jelly
Authors: Kamakura Masaki , Moriyama Tatsuya , Sakaki Toshiyuki
Published: December 2006

Royal jelly (RJ) has various pharmacological actions, including hypolipidaemic, hypocholesterolaemic and anti-atherosclerotic effects, in experimental animals but the molecular mechanisms involved remain unclear. Here, we investigated changes in the expression of lipid metabolism-associated genes in the liver of RJ-treated mice by means of a DNA microarray technique to obtain clues to the mechanism of the hypocholesterolaemic action of RJ. We compared the hepatic gene expression profiles in three groups of mice fed a diet containing 5% RJ, a diet containing 5% RJ stored at 40°C for 7 days (40-7d RJ) or a control diet which provided the same total energy as the other diets. RJ decreased gene expression of squalene epoxidase (SQLE), which is a key enzyme in cholesterol biosynthesis, and sterol regulatory element-binding protein (SREB)-1, which may be a transcriptional factor of SQLE. It increased gene expression of low-density lipoprotein receptor (LDLR), which is involved in cholesterol incorporation in liver. Thus, the hypocholesterolaemic action of RJ appears to be associated with a decrease of SQLE and an increase of LDLR in mice.
Rap1: a key regulator in cell-cell junction formation
Authors: Kooistra Matthijs R. H. , Dubé Nadia , Bos Johannes L.
Published: December 2006

Rap1 is a Ras-like small GTPase that is activated by many extracellular stimuli and strongly implicated in the control of integrin-mediated cell adhesion. Recent evidence indicates that Rap1 also plays a key role in formation of cadherin-based cell-cell junctions. Indeed, inhibition of Rap1 generates immature adherens junctions, whereas activation of Rap1 tightens cell-cell junctions. Interestingly, Rap1 guanine nucleotide exchange factors, such as C3G and PDZ-GEF, are directly linked to E-cadherin or to other junction proteins. Furthermore, several junction proteins, such as afadin/AF6 and proteins controlling the actin cytoskeleton, function as effectors of Rap1. These findings point to a role of Rap1 in spatial and temporal control of cell-cell junction formation.
A new activating role for CO in cardiac mitochondrial biogenesis
Authors: Suliman Hagit B. , Carraway Martha S. , Tatro Lynn G. , Piantadosi Claude A.
Published: December 2006

To investigate a possible new physiological role of carbon monoxide (CO), an endogenous gas involved in cell signaling and cytotoxicity, we tested the hypothesis that the mitochondrial generation of reactive oxygen species by CO activates mitochondrial biogenesis in the heart. In mice, transient elevations of cellular CO by five- to 20-fold increased the copy number of cardiac mitochondrial DNA, the content of respiratory complex I-V and interfibrillar mitochondrial density within 24 hours. Mitochondrial biogenesis is activated by gene and protein expression of the nuclear respiratory factor 1 (NRF1) and NRF2, of peroxisome proliferator-activated receptor gamma co-activator-1α, and of mitochondrial transcription factor A (TFAM), which augmented the copy number of mitochondrial DNA (mtDNA). This is independent of nitric oxide synthase (NOS), as demonstrated by the identical responses in wild-type and endothelial NOS (eNOS)-deficient mice, and by the inhibition of inducible NOS (iNOS). In the heart and in isolated cardiomyocytes, CO activation involved both guanylate cyclase and the pro-survival kinase Akt/PKB. Akt activation was facilitated by mitochondrial binding of CO and by production of hydrogen peroxide (H2O2). Interference with Akt activity by blocking PI 3-kinase and by mitochondrial targeting of catalase to scavenge H2O2 prevented binding of NRF1 to the Tfam promoter, thereby connecting mitochondrial H2O2 to the pathway leading to mtDNA replication. The findings disclose mitochondrial CO and H2O2 as new activating factors in cardiac mitochondrial biogenesis.
Synaptotagmin 3 deficiency in T cells impairs recycling of the chemokine receptor CXCR4 and thereby inhibits CXCL12 chemokine-induced migration
Authors: Masztalerz Agnieszka , Zeelenberg Ingrid S. , Wijnands Yvonne M. , de Bruijn Rosalie , Drager Angelika M. , Janssen Hans , Roos Ed
Published: December 2006

Synaptotagmins regulate vesicle trafficking and fusion of vesicles with membranes – processes that have been implicated in cell migration. We therefore hypothesized that synaptotagmins play a role in T-cell migration. Amongst synaptotagmins 1-11, we found synaptotagmin 3 (SYT3) to be the only one that is expressed in T cells. CXCR4-triggered migration was inhibited by antisense synaptotagmin 3 mRNA and by the isolated C2B domain, known to impair oligomerization of all synaptotagmins, but not by a C2B mutant that binds Ca2+ but does not block oligomerization. The C2B domain also blocked CXCR4-triggered actin polymerization and invasion. However, CXCR4-dependent adhesion in flow was not affected. Surprisingly, we found that little or no SYT3 is present near the plasma membrane but that it is mainly localized in multivesicular bodies, which also contained much of the CXCR4. Impaired SYT3 function blocked CXCR4 recycling and thus led to reduced surface levels of CXCR4. Migration was restored by overexpression of CXCR4. We conclude that STT3 is essential for CXCR4 recycling in T cells and thereby for the maintenance of high CXCR4 surface levels required for migration.
Synthesis of Unsymmetrically and Highly Substituted Thiophenes Utilizing Regioselective Ring-expansion of gem-Dichlorocyclopropyl Ketones with Lawesson’s Reagent
Authors: Nagano Takao , Kimoto Hiroki , Nakatsuji Hidefumi , Motoyoshiya Jiro , Aoyama Hiromu , Tanabe Yoo , Nishii Yoshinori
Published: December 2006

Ring-expansion of aryl gem-dichlorocyclopropyl ketones 1 using Lawesson’s reagent afforded unsymmetrically and highly substituted 5-chloro and 3-chlorothiophenes 2 and 3 with excellent regioselectivity. The Suzuki–Miyaura coupling of 2 and 3 with PhB(OH)2 was successfully performed to give 2-aryl-3-methyl-5-phenylthiophenes 4 and 2-aryl-3-methyl-4,5-diphenylthiophenes 5, respectively.
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Hypertension Due to Primary Aldosteronism: A Case for Exclusion
Authors: Bubbar Carolyn D , Blackburn David F , Wilson Merne P , Wilson Thomas W
Published: December 2006

Aldosterone antagonists are the mainstay of therapy in patients with hypertension due to primary aldosteronism. However, in our experience, these patients are sometimes placed on angiotensin-converting enzyme (ACE) inhibitors in accordance with guidelines applying to the general hypertensive population. We believe this practice is inappropriate because of the inability of ACE inhibitors to lower blood pressure in patients with low renin levels. Furthermore, pleiotropic effects of ACE inhibitors are unlikely to provide significant benefits in the absence of blood pressure reduction. Therefore, ACE inhibitors should be discouraged for the majority of patients with primary aldosteronism, even in the face of renal or cardiac disease.
Short-Term Hemostatic Safety of Strontium Ranelate Treatment in Elderly Women with Osteoporosis
Authors: Halil Meltem , Cankurtaran Mustafa , Yavuz Burcu Balam , Ulger Zekeriya , Piskinpasa Serhan , Gedik Arzu , Haznedaroglu Ibrahim Celalettin , Kirazli Serafettin , Ariogul Servet
Published: December 2006

Background:

Strontium ranelate offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal osteoporosis. However, there are some data revealing an association between strontium ranelate treatment and increased incidence of venous thromboembolism (VTE), suggesting possible adverse prothrombotic effects of the drug.

Objective:

To assess the effect of strontium ranelate treatment on primary hemostasis, secondary hemostasis, and the natural anticoagulant defense system, together with prothrombotic markers, in elderly women with osteoporosis.

Methods:

This study was designed in a prospective manner. Thirty-five elderly women diagnosed with osteoporosis were included. During a 2 month treatment period, participants received strontium ranelate 2 g. Platelet Function Analyzer-100 (PFA-100) in vitro bleeding time was performed to depict primary hemostasis. Secondary hemostatic parameters including prothrombin time, international normalized ratio, activated partial thromboplastin time, anti-cardiolipine immunoglobulin (Ig) M and IgG, antiphospholipid IgM and IgG, protein C, protein S, anti-thrombin III, lupus anticoagulant, fibrinogen, thrombin, activated protein C resistance, and plasma levels of d-dimer were assessed. These parameters were tested before and after 2 month treatment with strontium ranelate.

Results:

Mean ± SD age of the patients was 72.82 ± 5.69 years. After 60 days of treatment, there was no statistically significant prolongation in PFA-100 in vitro bleeding time and no statistically significant change in the critical hemostatic parameters in patients receiving strontium ranelate that led to discontinuation of the treatment. None of the subjects developed clinical VTE during the 2 month period of strontium ranelate treatment.

Conclusions:

The hemostatic safety of strontium ranelate in the elderly population with osteoporosis was shown over 2 months of treatment; however, its long-term hemostatic safety should be evaluated further.
Memory for curvature of objects: Haptic touch vs. vision
Authors: Ittyerah Miriam , Marks Lawrence E.
Published: December 2006

The present study examined the role of vision and haptics in memory for stimulus objects that vary along the dimension of curvature. Experiment 1 measured haptic‐haptic (T‐T) and haptic‐visual (T‐V) discrimination of curvature in a short‐term memory paradigm, using 30‐second retention intervals containing five different interpolated tasks. Results showed poorest performance when the interpolated tasks required spatial processing or movement, thereby suggesting that haptic information about shape is encoded in a spatial‐motor representation. Experiment 2 compared visual‐visual (V‐V) and visual‐haptic (V‐T) short‐term memory, again using 30‐second delay intervals.

The results of the ANOVA failed to show a significant effect of intervening activity. Intra‐modal visual performance and cross‐modal performance were similar. Comparing the four modality conditions (inter‐modal V‐T, T‐V; intra‐modal V‐V, T‐T, by combining the data of Experiments 1 and 2), in a global analysis, showed a reliable interaction between intervening activity and experiment (modality). Although there appears to be a general tendency for spatial and movement activities to exert the most deleterious effects overall, the patterns are not identical when the initial stimulus is encoded haptically (Experiment 1) and visually (Experiment 2).
Is Tobacco Use a Problem Among Deaf College Students?
Authors: Berman Barbara A , Bernaards Coen A. , Eckhardt Elizabeth A , Kleiger Heidi B , Maucere Lauren , Streja Leanne , Wong Glenn , Barkin Shari , Bastani Roshan
Published: January 2007

College students' tobacco use poses a significant public health problem. Effective intervention requires understanding of this behavior among race/ethnic, cultural, and linguistic collegiate subgroups, including deaf and hard of hearing collegians. Findings from a first-ever tobacco-related survey among this understudied population are reported. The authors used written questionnaires and the Interactive Video Questionnaireâ¢, a multimedia computer technology developed for use with the deaf and hard of hearing, to interview 241 volunteers on seven California college campuses. They found lower self-reported current smoking prevalence (14.5%) relative to collegians in the general population, but considerable ever smoking (65.1%) and multiple types of Â­tobacco use (37.3%). The authors report on factors associated with tobacco use and on students' exposure to cigarette marketing, gaps experienced in receipt of antitobacco messages and services, and students' antitobacco intervention recommendations. Limitations of the research are described, including possible underreporting of participants' tobacco use.
Paine and Prejudice: Rhetorical Leadership through Perceptual Framing in Common Sense
Authors: Hoffman David C
Published: January 2007

This essay reviews the established case for the pivotal role played by Thomas Paine's pamphlet Common Sense in the American Revolution as well as the various explanations that have been proffered to account for its success: the time and place of its publication, Paine's style, Paine's ethos, and his use of psychology and ideology. To these accounts it adds the suggestion that Paine used the term "prejudice" to frame his readers' positive perception of monarchy and the British constitution, and negative perceptions of American independence, as distortions imposed by "habit and custom." In the process of making this case it explores the genealogy of the term "prejudice."
Delayed Development of Paget's Disease in Offspring Inheriting SQSTM1 Mutations
Authors: Bolland Mark J , Tong Pak Cheung , Naot Dorit , Callon Karen E , Wattie Diana J , Gamble Greg D , Cundy Tim
Published: December 2006

Familial Paget's disease is associated with mutations in SQSTM1. We compared the age at diagnosis and severity of Paget's disease in parents with SQSTM1 mutations to their offspring who inherited a mutation. At any given age, the offspring were less likely to be diagnosed with Paget's disease and had less severe disease than their parents.

Introduction: Mutations in sequestosome 1 (SQSTM1) occur in 25–50% of cases of familial Paget's disease and are thought to be disease-causing. We sought to determine whether there are differences in age at diagnosis and severity of disease in parents and their offspring who share the same genetic predisposition to Paget's disease.

Materials and Methods: Eighty-four offspring from 10 families (29 index patients with Paget's disease) with mutations in SQSTM1 were approached, and 58 agreed to participate. The ubiquitin-binding domain region of SQSTM1 was sequenced, and the presence or absence of the known mutation was established. The presence of Paget's disease in offspring who had inherited an SQSTM1 mutation was determined by bone scintigraphy and measurement of serum alkaline phosphatase (ALP).

Results: Twenty-three of 58 offspring had inherited a germline mutation in SQSTM1. The mean ALP was 77 U/liter in offspring with mutations and 72 U/liter in those without mutations (p = 0.84). Scintiscans from four offspring (mean age, 45 years; mean ALP, 139 U/liter; mean skeletal involvement, 6%) showed evidence of Paget's disease but were normal in the other 19 (mean age, 44 years; mean ALP, 64 U/liter). In comparison, in the 15 parents of the 23 offspring, the mean age of diagnosis was 48 years, the mean ALP was 850 U/liter, and the mean skeletal involvement was 30%. There was a 63% reduction in the risk of being diagnosed with Paget's disease at a comparable age in the offspring compared with the parents (p = 0.028).

Conclusions: Only 17% of offspring inheriting an SQSTM1 mutation had evidence of Paget's disease on scintigraphy, and this was diagnosed at a later age and was less extensive than in their affected parents. SQSTM1 thus shows incomplete penetrance. The data are consistent with the hypothesis that an environmental factor is important in the pathogenesis and clinical phenotype of familial Paget's disease and that exposure to this factor may be falling.
Is a School-Based Physical Activity Intervention Effective for Increasing Tibial Bone Strength in Boys and Girls?
Authors: Macdonald Heather M , Kontulainen Saija A , Khan Karim M , McKay Heather A
Published: December 2006

This 16-month randomized, controlled school-based study compared change in tibial bone strength between 281 boys and girls participating in a daily program of physical activity (Action Schools! BC) and 129 same-sex controls. The simple, pragmatic intervention increased distal tibia bone strength in prepubertal boys; it had no effect in early pubertal boys or pre or early pubertal girls.

Introduction: Numerous school-based exercise interventions have proven effective for enhancing BMC, but none have used pQCT to evaluate the effects of increased loading on bone strength during growth. Thus, our aim was to determine whether a daily program of physical activity, Action Schools! BC (AS! BC) would improve tibial bone strength in boys and girls who were pre- (Tanner stage 1) or early pubertal (Tanner stage 2 or 3) at baseline.

Materials and Methods: Ten schools were randomized to intervention (INT, 7 schools) or control (CON, 3 schools). The bone-loading component of AS! BC included a daily jumping program (Bounce at the Bell) plus 15 minutes/day of classroom physical activity in addition to regular physical education. We used pQCT to compare 16-month change in bone strength index (BSI, mg2/mm4) at the distal tibia (8% site) and polar strength strain index (SSIp, mm3) at the tibial midshaft (50% site) in 281 boys and girls participating in AS! BC and 129 same-sex controls. We used a linear mixed effects model to analyze our data.

Results: Children were 10.2 ± 0.6 years at baseline. Intervention boys tended to have a greater increase in BSI (+774.6 mg2/mm4; 95% CI: 672.7, 876.4) than CON boys (+650.9 mg2/mm4; 95% CI: 496.4, 805.4), but the difference was only significant in prepubertal boys (p = 0.03 for group × maturity interaction). Intervention boys also tended to have a greater increase in SSIp (+198.6 mm3; 95% CI: 182.9, 214.3) than CON boys (+177.1 mm3; 95% CI: 153.5, 200.7). Change in BSI and SSIp was similar between CON and INT girls.

Conclusions: Our findings suggest that a simple, pragmatic program of daily activity enhances bone strength at the distal tibia in prepubertal boys. The precise exercise prescription needed to elicit a similar response in more mature boys or in girls might be best addressed in a dose–response trial.
Enhanced Bone Regeneration Associated With Decreased Apoptosis in Mice With Partial HIF-1α Deficiency
Authors: Komatsu David E , Bosch-Marce Marta , Semenza Gregg L , Hadjiargyrou Michael
Published: December 2006

HIF-1α activates genes under hypoxia and was hypothesized to regulate bone regeneration. Surprisingly, HIF-1α+/− fracture calluses are larger, stronger, and stiffer than HIF-1α+/+ calluses because of decreased apoptosis. These data identify apoptosis inhibition as a means to enhance bone regeneration.

Introduction: Bone regeneration subsequent to fracture involves the synergistic activation of multiple signaling pathways. Localized hypoxia after fracture activates hypoxia-inducible factor 1α (HIF-1α), leading to increased expression of HIF-1 target genes. We therefore hypothesized that HIF-1α is a key regulator of bone regeneration.

Materials and Methods: Fixed femoral fractures were generated in mice with partial HIF-1α deficiency (HIF-1α+/−) and wildtype littermates (HIF-1α+/+). Fracture calluses and intact contralateral femurs from postfracture days (PFDs) 21 and 28 (N = 5–10) were subjected to μCT evaluation and four-point bending to assess morphometric and mechanical properties. Molecular analyses were carried out on PFD 7, 10, and 14 samples (N = 3) to determine differential gene expression at both mRNA and protein levels. Finally, TUNEL staining was performed on PFD 14 samples (N = 2) to elucidate differential apoptosis.

Results: Surprisingly, fracture calluses from HIF-1α+/− mice exhibited greater mineralization and were larger, stronger, and stiffer. Microarray analyses focused on hypoxia-induced genes revealed differential expression (between genotypes) of several genes associated with the apoptotic pathway. Real-time PCR confirmed these results, showing higher expression of proapoptotic protein phosphatase 2a (PP2A) and lower expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL2) in HIF-1α+/+ calluses. Subsequent TUNEL staining showed that HIF-1α+/+ calluses contained larger numbers of TUNEL+ chondrocytes and osteoblasts than HIF-1α+/− calluses.

Conclusions: We conclude that partial HIF-1α deficiency results in decreased chondrocytic and osteoblastic apoptosis, thereby allowing the development of larger, stiffer calluses and enhancing bone regeneration. Furthermore, apoptosis inhibition may be a promising target for developing new treatments to accelerate bone regeneration.
That Can't Be Right! What Causes Pragmatic Language Impairment Following Right Hemisphere Damage?
Authors: Martin Ingerith , McDonald Skye
Published: December 2006

Right hemisphere damage (RHD) following unilateral stroke is often associated with impairment of pragmatic language, specifically, the ability to comprehend inferences that arise from language used in context. Three kinds of cognitive deficits have been proposed to explain the pragmatic deficits in RHD individuals, impaired Theory of Mind (TOM), weak central coherence (CC), and impaired executive function (EF). This study aims to evaluate the explanatory ability of these theories in relation to the comprehension of nonliteral (ironic) jokes versus literal lies. Twenty-one RHD patients and 21 age-matched controls were assessed on tasks tapping TOM, CC processing and general inference ability (EF) and the comprehension of irony. Second-order TOM and EF were found to play a significant role. However, neither construct, either in isolation or combined, completely explained the poor performance of RHD patients on this task compared to control participants.
Analysing Conversational Discourse After Traumatic Brain Injury: Isn't It About Time?
Authors: Turkstra Lyn S. , Brehm Sarah E. , Montgomery Erwin B.
Published: December 2006

Most studies of conversational discourse in traumatic brain injury (TBI) have used summary measures averaged over time. These measures have yielded useful aggregate data but do not capture the temporal dynamics of interpersonal interactions. To fully characterise the conversational discourse of individuals with TBI, it may be useful to consider individuals and behaviours as systems changing over time. In this article, we review dynamic systems approaches that have been used to study conversational interactions, and present data to illustrate their potential utility in characterising the conversational discourse of individuals with TBI.
Androgens Regulate the Development of Neuropathology in a Triple Transgenic Mouse Model of Alzheimer's Disease
Authors: Rosario Emily R. , Carroll Jenna C. , Oddo Salvatore , LaFerla Frank M. , Pike Christian J.
Published: December 2006

Normal age-related testosterone depletion in men is a recently identified risk factor for Alzheimer's disease (AD), but how androgen loss affects the development of AD is unclear. To investigate the relationship between androgen depletion and AD, we compared how androgen status affects the progression of neuropathology in the triple transgenic mouse model of AD (3xTg-AD). Adult male 3xTg-AD mice were sham gonadectomized (GDX) or GDX to deplete endogenous androgens and then exposed for 4 months to either the androgen dihydrotestosterone (DHT) or to placebo. In comparison to gonadally intact 3xTg-AD mice, GDX mice exhibited robust increases in the accumulation of β-amyloid (Aβ), the protein implicated as the primary causal factor in AD pathogenesis, in both hippocampus and amygdala. In parallel to elevated levels of Aβ, GDX mice exhibited significantly impaired spontaneous alternation behavior, indicating deficits in hippocampal function. Importantly, DHT treatment of GDX 3xTg-AD mice attenuated both Aβ accumulation and behavioral deficits. These data demonstrate that androgen depletion accelerates the development of AD-like neuropathology, suggesting that a similar mechanism may underlie the increased risk for AD in men with low testosterone. In addition, our finding that DHT protects against acceleration of AD-like neuropathology predicts that androgen-based hormone therapy may be a useful strategy for the prevention and treatment of AD in aging men.
NR3A Modulates the Outer Vestibule of the “NMDA” Receptor Channel
Authors: Wada Akira , Takahashi Hiroto , Lipton Stuart A. , Chen H.-S. Vincent
Published: December 2006

Classical NMDA receptors (NMDARs), activated by glycine and glutamate, are heteromultimers comprised of NR1 and NR2 subunits. Coexpression of the novel NR3 family of NMDAR subunits decreases the magnitude of NR1/NR2 receptor-mediated currents or forms glycine-activated channels with the NR1 subunit alone. The second (M2) and third (M3) membrane segments of NR1 and NR2 subunits of classical NMDARs form the core of the channel permeation pathway. Structural information regarding NR1/NR3 channels remains unknown. Using theXenopusoocyte expression system and the SCAM (substituted cysteine accessibility method), we found that M3 segments of both NR1 and NR3A form a narrow constriction in the outer vestibule of the channel, which prevents passage of externally applied sulfhydryl-specific agents. The most internal reactive residue in each M3 segment is the threonine in the conserved SYTANLAAF motif. These threonines appear to be symmetrically aligned. Several NR3A M3 mutations change the behavior of NR1/NR3A channels. Unlike NR1, however, the M3 segment of NR3A does not undergo extensive molecular rearrangement during channel gating by added glycine. Additionally, in the M2 segment, our data suggest that the amino acid at the asparagine (N) site of NR1, but not NR3A, contributes to the selectivity filter of NR1/3A channels. We therefore conclude that NR3A modulates the NR1/NR3A permeation pathway via a novel mechanism of forming a narrow constriction at the outer channel vestibule. This modified channel vestibule may also explain the dominant-negative effect of the NR3 subunit on channel behavior when coexpressed with NR1 and NR2 subunits.
Brain Connectivity Related to Working Memory Performance
Authors: Hampson Michelle , Driesen Naomi R. , Skudlarski Pawel , Gore John C. , Constable R. Todd
Published: December 2006

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task.
Deletion of theTtf1Gene in Differentiated Neurons Disrupts Female Reproduction without Impairing Basal Ganglia Function
Authors: Mastronardi Claudio , Smiley Gregory G. , Raber Jacob , Kusakabe Takashi , Kawaguchi Akio , Matagne Valerie , Dietzel Anja , Heger Sabine , Mungenast Alison E. , Cabrera Ricardo , Kimura Shioko , Ojeda Sergio R.
Published: December 2006

Thyroid transcription factor 1 (TTF1) [also known as Nkx2.1 (related to the NK-2 class of homeobox genes) and T/ebp (thyroid-specific enhancer-binding protein)], a homeodomain gene required for basal forebrain morphogenesis, remains expressed in the hypothalamus after birth, suggesting a role in neuroendocrine function. Here, we show an involvement of TTF1 in the control of mammalian puberty and adult reproductive function. Gene expression profiling of the nonhuman primate hypothalamus revealed that TTF1 expression increases at puberty. Mice in which theTtf1gene was ablated from differentiated neurons grew normally and had normal basal ganglia/hypothalamic morphology but exhibited delayed puberty, reduced reproductive capacity, and a short reproductive span. These defects were associated with reduced hypothalamic expression of genes required for sexual development and deregulation of a gene involved in restraining puberty. No extrapyramidal impairments associated with basal ganglia dysfunction were apparent. Thus, although TTF1 appears to fulfill only a morphogenic function in the ventral telencephalon, once this function is satisfied in the hypothalamus, TTF1 remains active as part of the transcriptional machinery controlling female sexual development.
Hypocretin/Orexin Overexpression Induces An Insomnia-Like Phenotype in Zebrafish
Authors: Prober David A. , Rihel Jason , Onah Anthony A. , Sung Rou-Jia , Schier Alexander F.
Published: December 2006

As many as 10% of humans suffer chronic sleep disturbances, yet the genetic mechanisms that regulate sleep remain essentially unknown. It is therefore crucial to develop simple and cost-effective vertebrate models to study the genetic regulation of sleep. The best characterized mammalian sleep/wake regulator is hypocretin/orexin (Hcrt), whose loss results in the sleep disorder narcolepsy and that has also been implicated in feeding behavior, energy homeostasis, thermoregulation, reward seeking, addiction, and maternal behavior. Here we report that the expression pattern and axonal projections of embryonic and larval zebrafish Hcrt neurons are strikingly similar to those in mammals. We show that zebrafish larvae exhibit robust locomotive sleep/wake behaviors as early as the fifth day of development and that Hcrt overexpression promotes and consolidates wakefulness and inhibits rest. Similar to humans with insomnia, Hcrt-overexpressing larvae are hyperaroused and have dramatically reduced abilities to initiate and maintain rest at night. Remarkably, Hcrt function is modulated by but does not require normal circadian oscillations in locomotor activity. Our zebrafish model of Hcrt overexpression indicates that the ancestral function of Hcrt is to promote locomotion and inhibit rest and will facilitate the discovery of neural circuits, genes, and drugs that regulate Hcrt function and sleep.
Magnetic Memory: A Day-Long Video Tribute to Nam June Paik
Authors: Hamlyn Nicky
Published: December 2006

ABSTRACT This review of video work by Nam June Paik traces the artist's origins in the European Fluxus movement before his move to New York, where he lived until his death (in 2006) and collaborated with other artists including John Cage, Charlotte Moorman, and Yoko Ono.
LIBERATING IMAGES? Samuel Fuller's Film of Falkenau Concentration Camp
Authors: ORGERON MARSHA
Published: December 2006

ABSTRACT This article examines a neglected but important film from Samuel Fuller's formative years: the 16mm footage he shot in 1945, depicting a funeral ritual following his infantry division's liberation of Falkenau concentration camp. The footage provides a fascinating glimpse into the director's past and into World War II history.
Visions of Salome: The Femme Fatale in American Popular Songs before 1920
Authors: HAMBERLIN LARRY
Published: December 2006

This article documents representations of Salome, an archetypal exotic femme fatale, in American popular songs of the early twentieth century. The production of Salome songs began shortly after the sensational 1907 U.S. premiere of Richard Strauss's Salome at New York's Metropolitan Opera. Vaudeville performers, beginning with the Met's own prima ballerina, capitalized on the ensuing fad for Salome dances, which the New York Times called “Salomania.” Relevant songs and dances figured in musical comedies and revues until some time after the return of Strauss's opera to the New York stage, in the 1909 Manhattan Opera Company production with Mary Garden in the title role. Through the next decade, musical, lyrical, and illustrative tropes that originated in the Salome songs became disassociated from the figure of Salome, gradually merging into “oriental fox-trots” and exotic romance songs. The topical humor of the Salome songs suggests that American audiences were skeptical of the allure of orientalist fantasy, then at its height in Europe, and that an unwillingness to grant artistic legitimacy to Salome's religious-themed eroticism is an important marker of the American reception of works such as Strauss's.
Biofilm and mercury availability as key factors for mercury accumulation in fish (Curimata cyprinoides) from a disturbed amazonian freshwater system
Authors: Dominique Yannick , Maury-Brachet Régine , Muresan Bogdan , Vigouroux Régis , Richard Sandrine , Cossa Daniel , Mariotti André , Boudou Alain
Published: December 2006

The Petit-Saut hydroelectric reservoir was filled in 1994 on the Sinnamary River in French Guiana (Amazonian basin). Flooding of the equatorial rain forest led to anoxia in most of the water column and enhanced mercury methylation in the reservoir hypolimnion. We selected the benthivorous/omnivorous fish species Curimata cyprinoides to investigate total mercury and methylmercury (MeHg) bioavailability and bioaccumulation capacities in the reservoir and downstream in the Sinnamary River. Mercury concentrations in the dorsal skeletal muscle were 10-fold higher in fish from the downstream zone. Stomach contents and stable nitrogen and carbon isotope ratios showed that biofilms and the associated invertebrate communities represented important food sources at the two sites. The δ13C measurements indicated that biofilms in the flooded forest zone of the reservoir consist of endogenous primary producers; downstream, they are based on exogenous organic matter and microorganisms, mainly from the anoxic layers of the reservoir. Total mercury and MeHg concentrations in the biofilms and associated invertebrates were much higher at the downstream site compared to concentrations at the reservoir. Our results clearly show the importance of MeHg export from the anoxic layers of this tropical reservoir. We conclude that differences between biofilm composition and MeHg concentrations in the ingested food could explain the marked differences observed between mercury levels in fish.
Establishing cause–effect relationships in hydrocarbon-contaminated sediments using a sublethal response of the benthic marine alga,EntomoneisCFPunctulata
Authors: Simpson Stuart L. , Micevska Tina , Adams Merrin S. , Stone Alexandria , Maher William A.
Published: December 2006

A sublethal whole-sediment toxicity test that uses flow cytometry to measure inhibition of esterase activity in the marine microalga Entomoneis cf punctulata was applied to the assessment of hydrocarbon-contaminated sediments and toxicity identification and evaluation (TIE). Concentration–response relationships were developed, and a 20% effect concentration for total polycyclic aromatic hydrocarbons (PAHs) of 60 mg/kg normalized to 1% total organic carbon was calculated. Relationships between toxic effects and sediment organic carbon concentrations, organic carbon forms (e.g., black carbon), and sediment particle size indicated that further normalization of hydrocarbon concentrations to sediment particle size may improve concentration–responserelationships. The algal toxicity test was applied as a rapid whole-sediment TIE procedure that involved the addition to sediment of powdered coconut charcoal (PCC), a hydrophobic, carbon-based material that strongly adsorbs PAHs and decreases the pore-water exposure pathway. Sediments with PCC concentrations of up to 15% (w/w) provided acceptable responses in control sediments. For six sediments with total PAH concentrations of 1,060, 4,060, 5,120, 9,150, 9,900, and 15,900 mg/kg, inhibition of E. cf punctulata esterase activity (% of control) was 75, 97, 94, 93, 100, and 97%, respectively. Following a 15% PCC amendment to these sediments, inhibition of esterase activity was 0, 1, 11, 69, 32, and 68%, respectively, indicating a decrease in toxicity in all sediments. Because the alga E. cf punctulata is exposed to toxicants via both pore water and overlying water, the reduction in toxicity achieved by 15% PCC additions can be related to the efficient removal of dissolved hydrocarbons released from sediment particles. The sediment–PCC manipulations coupled with algal whole-sediment toxicity tests provided an effective and rapid TIE method to determine whether hydrocarbon contaminants are responsible for toxicity in sediments.