bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-221 suppresses ICAM-1 translation and regulates interferon-γ-induced ICAM-1 expression in human cholangiocytes
Authors: Hu Guoku , Gong Ai-Yu , Liu Jun , Zhou Rui , Deng Caishu , Chen Xian-Ming
Published: January 2010

Aberrant cholangiocyte reactions in response to inflammatory stimuli are important pathogenic factors for the persistent biliary inflammation in patients with cholangiopathies. Overexpression of intercellular cell adhesion molecule-1 (ICAM-1) in cholangiocytes is a common pathological feature in inflammatory cholangiopathies and can promote cholangiocyte interactions with effector lymphocytes in the portal region. In this study, we tested the involvement of miRNA-mediated posttranscriptional regulation in IFN-γ-induced ICAM-1 expression in cholangiocytes. Using both immortalized and nonimmortalized human cholangiocyte cell lines, we found that IFN-γ activated ICAM-1 transcription and increased ICAM-1 protein expression. Inhibition of ICAM-1 transcription could only partially block IFN-γ-induced ICAM-1 expression at the protein level. In silico target prediction analysis revealed complementarity of miR-221 to the 3′-untranslated region of ICAM-1 mRNA. Targeting of ICAM-1 3′-untranslated region by miR-221 resulted in translational repression in cholangiocytes but not ICAM-1 mRNA degradation. Functional inhibition of miR-221 with anti-miR-221 induced ICAM-1 protein expression. Moreover, IFN-γ stimulation decreased miR-221 expression in cholangiocytes in a signal transducer and activator of transcription 1-dependent manner. Transfection of miR-221 precursor abolished IFN-γ-stimulated ICAM-1 protein expression. In addition, miR-221-mediated expression of ICAM-1 on cholangiocytes showed a significant influence on the adherence of cocultured T cells. These findings indicate that both transcriptional and miRNA-mediated posttranscriptional mechanisms are involved in IFN-γ-induced ICAM-1 expression in human cholangiocytes, suggesting an important role for miRNAs in the regulation of cholangiocyte inflammatory responses.
Implantation increases tensile strength and collagen content of self-assembled tendon constructs
Authors: Calve Sarah , Lytle Ian F. , Grosh Karl , Brown David L. , Arruda Ellen M.
Published: January 2010

Tissue-engineered tendons, derived from an autologous cell source, have the potential to provide an ideal replacement graft that is biologically compatible and has the ability to adapt to the specific mechanical requirements of the in vivo environment. Scaffold-free tendon constructs have been successfully engineered in vitro. However, when compared against native tendons the constructs demonstrate both a lower tensile strength and collagen content. We hypothesized that the in vitro environment lacks certain environmental stimuli and that implantation in vivo would facilitate the maturation of engineered tissues. Using primary Achilles tendon fibroblasts from adult rats, self-organizing constructs were created in vitro. Tendon constructs were implanted subcutaneously into the groins of adult rats for 4 wk, while controls remained in vitro. Implanted constructs increased in stiffness by three orders of magnitude when compared with the in vitro controls (7,500 vs. 22.3 kPa). This increase in tangent modulus correlated with a significant increase in collagen content, as measured by hydroxyproline concentration, from 3.9% for the in vitro controls to 22.7% in the in vivo conditioned group. In addition, collagen fiber diameter increased from 22.0 to 75.4 nm as a result of in vivo implantation. The tensile strength and collagen content of in vivo conditioned constructs were similar to the values determined for neonatal rat tibialis anterior tendons.
Ultraendurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle
Authors: Sahlin Kent , Shabalina Irina G. , Mattsson C. Mikael , Bakkman Linda , Fernström Maria , Rozhdestvenskaya Zinaida , Enqvist Jonas K. , Nedergaard Jan , Ekblom Björn , Tonkonogi Michail
Published: January 2010

Exercise-induced oxidative stress is important for the muscular adaptation to training but may also cause muscle damage. We hypothesized that prolonged exercise would increase mitochondrial production of reactive oxygen species (ROS) measured in vitro and that this correlates with oxidative damage. Eight male athletes (24–32 yr) performed ultraendurance exercise (kayaking/running/cycling) with an average work intensity of 55% V̇o2peak for 24 h. Muscle biopsies were taken from vastus lateralis before exercise, immediately after exercise, and after 28 h of recovery. The production of H2O2 was measured fluorometrically in isolated mitochondria with the Amplex red and peroxidase system. Succinate-supported mitochondrial H2O2 production was significantly increased after exercise (73% higher, P = 0.025) but restored to the initial level at recovery. Plasma level of free fatty acids (FFA) increased fourfold and exceeded 1.2 mmol/l during the last 6 h of exercise. Plasma FFA at the end of exercise was significantly correlated to mitochondrial ROS production ( r = 0.74, P < 0.05). Mitochondrial content of 4-hydroxy-nonenal-adducts (a marker of oxidative damage) was increased only after recovery and was not correlated with mitochondrial ROS production. Total thiol group level and glutathione peroxidase activity were elevated after recovery. In conclusion, ultraendurance exercise increases ROS production in isolated mitochondria, but this is reversed after 28 h recovery. Mitochondrial ROS production was not correlated with oxidative damage of mitochondrial proteins, which was increased at recovery but not immediately after exercise.
Glia modulation of the extracellular milieu as a factor in central CO2chemosensitivity and respiratory control
Authors: Erlichman Joseph S. , Leiter J. C.
Published: January 2010

We discuss the influence of astrocytes on respiratory function, particularly central CO2chemosensitivity. Fluorocitrate (FC) poisons astrocytes, and studies in intact animals using FC provide strong evidence that disrupting astrocytic function can influence CO2chemosensitivity and ventilation. Gap junctions interconnect astrocytes and contribute to K+homeostasis in the extracellular fluid (ECF). Blocking gap junctions alters respiratory control, but proof that this is truly an astrocytic effect is lacking. Intracellular pH regulation of astrocytes has reciprocal effects on extracellular pH. Electrogenic sodium-bicarbonate transport (NBCe) is present in astrocytes. The activity of NBCe alkalinizes intracellular pH and acidifies extracellular pH when activated by depolarization (and a subset of astrocytes are depolarized by hypercapnia). Thus, to the extent that astrocytic intracellular pH regulation during hypercapnia lowers extracellular pH, astrocytes will amplify the hypercapnic stimulus and may influence central chemosensitivity. However, the data so far provide only inferential support for this hypothesis. A lactate shuttle from astrocytes to neurons seems to be active in the retrotrapezoid nucleus (RTN) and important in setting the chemosensory stimulus in the RTN (and possibly other chemosensory nuclei). Thus astrocytic processes, so vital in controlling the constituents of the ECF in the central nervous system, may profoundly influence central CO2chemosensitivity and respiratory control.
Differences between Clinical Subspecialties in the Outpatient Evaluation and Treatment of Dementia in an Academic Medical Center
Authors: Kalkonde Yogeshwar V. , Pinto-Patarroyo Gineth P. , Goldman Tatiana , Strutt Adriana M. , York Michele K. , Kunik Mark E. , Schulz Paul E.
Published: January 2010

Background: Professional organizations have recommended guidelines for the optimal investigation and management of dementia. It is unknown whether physicians from different subspecialties investigate and treat dementia in the same manner or according to these guidelines. Methods: We screened 1,401 charts of patients who were seen in neurology, mental health, geropsychiatry and geriatrics clinics. The charts of 410 patients who were diagnosed with dementia were reviewed in detail to determine how they were evaluated and managed. Results: Overall, 40% of patients received a complete laboratory workup to rule out comorbidities, 70% of patients received neuroimaging with either computerized tomography or magnetic resonance imaging of the brain, 63% had a depression screen and 38% of patients underwent neuropsychological testing. However, the frequency with which they were obtained differed significantly across clinics (p < 0.05). The frequency with which acetylcholinesterase inhibitors (CHEIs) were used did not differ significantly (p = 0.07) for patients with Alzheimer’s disease (AD), but differed significantly (p < 0.05) for dementia categories where CHEIs are thought to be useful (AD, vascular dementia and dementia with Lewy bodies). Conclusions: There were significant differences between subspecialties in the evaluation and treatment of dementia. It will be important to investigate whether these differences alter patient outcomes.
Metabolic Compensation and Depression in Alzheimer’s Disease
Authors: Caroli A. , Lorenzi M. , Geroldi C. , Nobili F. , Paghera B. , Bonetti M. , Cotelli M. , Frisoni G.B.
Published: January 2010

Background/Aims: The aim of this study was to map metabolic compensation and depression in Alzheimer’s disease (AD) on a voxel-by-voxel basis. Methods: Twenty-one healthy elderly subjects and 25 AD patients underwent cerebral MR and FDG-PET imaging. All images were processed with SPM2, and whole-brain gray matter (GM) atrophy and hypometabolism maps were computed. Metabolic compensation and depression were assessed using Biological Parametric Mapping software. Results: GM atrophy and hypometabolism mapped to similar regions, with varying degrees of severity. Significant metabolic compensation was found in the amygdala, while exceeding hypometabolism was mainly located in the posterior cingulate cortex. Conclusion: Metabolic depression can be due to both distant effects of atrophy and to additional hypometabolism-inducing factors, such as amyloid deposition. Conversely, metabolic compensation could reflect spared synaptic plasticity of the surviving neurons. The investigation of the metabolic compensation mechanism could help in the comprehension of the AD underlying pathology.
Helicobacter pylori Eradication Prevents Extension of Intestinalization Even in the High-Risk Group for Gastric Cancer
Authors: Shiotani Akiko , Nishi Ryuji , Uedo Noriya , Iishi Hiroyasu , Tsutsui Hideaki , Ishii Manabu , Imamura Hiroshi , Kamada Tomoari , Hata Jiro , Haruma Ken
Published: January 2010

Background/Aims: CDX2 is associated with the intestinal phenotype in the gastrointestinal tracts and is expressed in the intestinal type of gastric cancer. Helicobacter pylori-associated atrophic gastritis is characterized by aberrant expression of CDX2. The aim was to investigate the effects of eradication to the expression of genes related to the gastric and intestinal phenotype including CDX2. We compared the effect of eradication between the patients at high risk for gastric cancer and controls. Methods: 20 patients with endoscopic resection for early gastric cancer and 12 sex- and age-matched controls were studied. CDX2 and mucin mRNA expressions were examined using whole biopsy specimens and microdissected gastric glands taken from corpus lesser and greater curves before and 1 year after eradication. Results:CDX2 and MUC2 expressions in the cancer group were significantly higher than in the controls and were significantly decreased after eradication. MUC5AC (p = 0.01) and MUC6 (p = 0.02) expression significantly increased in the control group; the difference between the two groups became significant after eradication. CDX2 expression in the glands without goblet cells was detectable and disappeared after eradication. Conclusion:H. pylori eradication can reverse gastric phenotype and diminish aberrant CDX2 expression in the early stage of intestinalization.
Factor Analysis of the Brief Agitation Rating Scale in a Large Sample of Norwegian Nursing Home Patients
Authors: Sommer Oskar H. , Kirkevold Øyvind , Cvancarova Milada , Engedal Knut
Published: January 2010

Background: Agitation and aggression are prevalent in dementia and put heavy strains on caregivers. Validated assessment tools measuring these symptoms are required to evaluate patients before therapy and during the follow-up period. Given the daily routine in nursing homes, abbreviated instruments are preferable. The Brief Agitation Rating Scale (BARS) is a short form of the Cohen-Mansfield Agitation Inventory. Our aim was to examine the Norwegian version of the BARS by performing a factor analysis. Methods: The data came from 1,870 nursing home patients. The primary caregivers were interviewed by research nurses using the Clinical Dementia Rating Scale, Lawton’s Physical Self-Maintenance Scale and the BARS. Results: The exploratory factor analysis of the BARS revealed 3 dimensions: physically aggressive behavior, physically nonaggressive behavior and verbal agitation. Linear regression analysis showed that reduced functioning in activities of daily living was associated with physically aggressive behavior and verbal agitation, whereas increased severity of dementia and better functioning in activities of daily living were related to physically nonaggressive behavior. In addition, verbal agitation was positively related to a higher number of drugs being taken per day. Conclusions: The factor analyses confirmed that the Norwegian version of the BARS measures the clinically relevant dimensions of agitation in dementia.
Refractory Acne and 21-Hydroxylase Deficiency in a Selected Group of Female Patients
Authors: Caputo Valentina , Fiorella Santi , Curiale Salvatrice , Caputo Alfredo , Niceta Marcello
Published: January 2010

Background: Excessive androgen production, suspected in women when acne is accompanied by hirsutism and menstrual irregularities, may be due to congenital adrenal hyperplasia. This inherited disorder of cortisol biosynthesis is caused in more than 90–95% of all cases by 21-hydroxylase deficiency (21-OHD). The steroid 21-hydroxylase gene (CYP21) has a high degree of variability. Objective: This study was conducted to evaluate CYP21 gene mutations in a selected group of women with papulopustular and comedonal acne refractory to treatment, irregular menses and hirsutism. Methods: 30 out of 61 women enrolled underwent pelvic ultrasound examination and hormonal screening. In 9 patients with a polycystic ovary and hormonal pattern of adrenal hyperandrogenism a significant elevation of adrenocorticotropic hormone (ACTH) stimulated 17-hydroxyprogesterone was detected. These women positive in the ACTH stimulation test were submitted to CYP21 gene analysis. Results: Genetic testing revealed several different point mutations and demonstrated that a cohort of patients resistant to acne therapy can be carriers or affected by non-classical 21-OHD (late onset). Conclusion: Persistent acne can be the unique presenting sign of non-classical 21-OHD. Evaluation of CYP21 gene mutations may identify female carriers or patients for genetic counselling.
Passive Smoke Exposure and Circulating Carotenoids in the CARDIA Study
Authors: Widome Rachel , Jacobs, Jr. David R. , Hozawa Atsushi , Sijtsma Femke , Gross Myron , Schreiner Pamela J. , Iribarren Carlos
Published: January 2010

Background/Aims: Our objective was to assess associations between passive smoke exposure in various venues and serum carotenoid concentrations. Methods: CARDIA is an ongoing longitudinal study of the risk factors for subclinical and clinical cardiovascular disease. At baseline in 1985/1986, serum carotenoids were assayed and passive smoke exposure inside and outside of the home and diet were assessed by self-report. Our analytic sample consisted of 2,633 black and white non-smoking adults aged 18–30 years. Results: Greater total passive smoke exposure was associated with lower levels of the sum of the three provitamin A carotenoids, α-carotene, β-carotene, and β-cryptoxanthin (–0.048 nmol/l per hour of passive smoke exposure, p = 0.001), unassociated with lutein/zeaxanthin, and associated with higher levels of lycopene (0.027 nmol/l per hour of passive smoke exposure, p = 0.010) after adjustment for demographics, diet, lipid profile, and supplement use. Exposure in both home and non-home spaces was also associated with lower levels of the provitamin A carotenoid index. Conclusion: Cross-sectionally, in 1985/86, passive smoke exposure in various venues was associated with reduced levels of provitamin A serum carotenoids.
Effect of Soybeans and Sword Beans on Bone Metabolism in a Rat Model of Osteoporosis
Authors: Byun Jae Soon , Lee Sang Sun
Published: January 2010

Background/Aims: Soy isoflavones have been reported to prevent bone loss in rat models of osteoporosis. However, the effect of the natural soybeans that people consume in their diet needs to be explored. In the present study, we evaluated the effects of yellow and black soybeans (Glycine max), and sword beans (Canavalia gladiate) on bone mineral density (BMD), bone mineral content (BMC), and bone biomarkers in ovariectomized (OVX) rats. Methods: Seven-week-old female Sprague-Dawley rats were raised for 2 weeks on a calcium-free diet based on the American Institute of Nutrition (AIN)-93M diets. All the rats received OVX, were randomized to one of four groups, and given one of the diets supplemented with casein, yellow soybean, black soybean, and sword bean for 10 weeks. BMD, BMC, osteocalcin (OC; a bone formation biomarker), deoxypyridinoline (DPD; a bone resorption biomarker), and TNF-α (a bone resorption cytokine) were assessed. Results: In the femur and lumbar spine, BMD and BMC were significantly higher in the various bean groups than in the casein group. Among the bean groups, femur and spine BMD were significantly higher in the yellow soybean and sword bean groups than in the black soybean group. Femur BMC was the highest in the yellow soybean group, and spine BMC was not significantly different between the various bean groups. Plasma OC concentrations and urinary DPD excretion were significantly higher in the casein group than in the various bean groups. The sword bean group showed significantly lower OC and DPD levels than the yellow and black soybean groups. There were no significant differences between the yellow and black soybean groups. TNF-α concentrations were not significantly different between the four groups. Conclusion: Consumption of yellow and black soybeans, and sword beans had a definite protective effect on bone loss in OVX rats by inhibiting bone turnover and preventing bone resorption. Furthermore, consumption of sword beans may help prevent postmenopausal osteoporosis.
Tissue Healing during Degradation of a Long-Lasting Bioresorbable γ-Ray-Sterilised Poly(Lactic Acid) Mesh in the Rat: A 12-Month Study
Authors: de Tayrac R. , Letouzey V. , Garreau H. , Guiraud I. , Vert M. , Mares P.
Published: January 2010

Aim: The purpose was to evaluate soft-tissue healing after poly(lactic acid) (PLA94) mesh implantation in a rat model. Methods: Full-thickness abdominal wall defects were created in 108 Wistar rats, and reconstructed with 83 PLA94 and 25 lightweight polypropylene (PPL) meshes. The meshes were previously γ-ray sterilised with 25, 75 or 125 kGy to accelerate PLA94 degradation. Results: The inflammatory response in PLA94 was significantly less pronounced and collagen organisation significantly better than in PPL. The higher the level of γ-radiation, the higher the incidence of abdominal wall herniation (22.2, 31.3 and 52.6% with 25, 75 and 125 kGy, respectively). No herniation occurred in the PPL group. Tensile strength was dramatically reduced after γ-ray-sterilised PLA94 mesh implantation. Conclusion: The γ-ray-sterilised PLA94 mesh was poor in preventing abdominal wall hernia recurrences in a rat model.
Menstrual Variation in Experimental Pain: Correlation with Gonadal Hormones
Authors: Teepker M. , Peters M. , Vedder H. , Schepelmann K. , Lautenbacher S.
Published: January 2010

Background: The results of studies examining the response to experimental pain during the menstrual cycle are conflicting because of differences in the definitions of the menstrual period, outcome measures and types of experimental pain stimulation. So far, there have been only a few studies correlating experimental pain with the levels of gonadal hormones over the menstrual cycle. Therefore, we assessed the responses to multiple experimental pain stimuli during the menstrual cycle and computed their correlations with the salivary concentrations of the gonadal hormones estrogen and testosterone. Methods: Twenty-four healthy and regularly menstruating women between 20 and 41 years old took part in the study. Detection thresholds (warmth, cold and electrical current) and pain thresholds (cold, heat, pressure and electrical current) were assessed on days 1, 4, 14 and 22 of the menstrual cycle. In each session, salivary samples were collected for the determination of the physiological estrogen 17β-estradiol, progesterone and testosterone. Progesterone was used exclusively to verify regular menstrual cycling. Results: Significant variations in pain thresholds for cold, pressure and electrical stimuli were observed over the menstrual cycle with the highest thresholds on day 22, except for the cold pain thresholds, which peaked on day 14. There were no such changes regarding heat pain and all the detection thresholds. The correlations separately computed for each of the 4 days between salivary estrogen as well as testosterone on the one hand and the detection or pain thresholds on the other hand failed to show significant levels, except for the coupling of testosterone and electrical pain thresholds on day 1. Conclusions: The pain thresholds for all the physical stressors increased after menstruation. The acrophases were located in the follicular (cold pain threshold) or in the luteal phase (pressure and electrical pain thresholds). The results of our correlation analyses indicate only minimal influences of the physiological levels of gonadal hormones on pain sensitivity in women.
Genetic Variation in the Inwardly Rectifying K+ Channel Subunits KCNJ3 (GIRK1) and KCNJ5 (GIRK4) in Patients with Sinus Node Dysfunction
Authors: Holmegard Haya N. , Theilade Juliane , Benn Marianne , Duno Morten , Haunso Stig , Svendsen Jesper H.
Published: January 2010

Background: Sinus node dysfunction (SND) is a heterogeneous disorder of unknown etiology characterized by a variety of supraventricular arrhythmias with symptoms of syncope, palpitations, and dizziness. The mechanism underlying the abnormal rhythm is incompletely understood. Objective: Because vagal stimulation and acetylcholine (ACh) affect the function of pacemaker cells, we hypothesized that genetic variation in the genes encoding the ACh-activated K+ channels, the KACh channels, could be involved in the pathogenesis of SND. Methods and Results: We screened 184 patients listed in the pacemaker registry of the Copenhagen University Hospital aged <60 years at pacemaker implantation for SND in the period 1982–2005. Forty-three patients fulfilled the following inclusion criteria: documented sinus arrest, asystole, or extreme sinus bradycardia. The coding sequences of KCNJ3 and KCNJ5, encoding the main subunits of the KACh channels, were re-sequenced. We identified several known single nucleotide polymorphisms in KCNJ3 and KCNJ5, but no mutations in either of the genes. Conclusions: Genetic variation in KCNJ3 and KCNJ5 encoding the subunits of the KACh channels is apparently not involved in the pathogenesis of SND.
Effects of Activated Protein C on Ventilator-Induced Lung Injury in Rats
Authors: Jiang Jiunn-Song , Chou Hsiu-Chu , Wang Leng-Fang , Lang Yaw-Dong , Chen Chung-Ming
Published: January 2010

Background: Mechanical ventilation with a high tidal volume (VT) increases lung and systemic plasminogen activator inhibitor (PAI)-1 levels and alveolar fibrin deposition. Activated protein C (APC) may decrease PAI activity in endothelial cell-conditioned medium and thus enhance fibrinolysis. Objectives: The aims of this study were to test the hypothesis that APC can neutralize PAI-1 activity and improve lung function in an animal model of ventilator-induced lung injury. Methods: Rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP; HVZP) protocol by a volume-cycled ventilator for 2 h at a VT of 30 ml/kg, a respiratory rate of 25 breaths/min, and an FiO2 of 0.21. Fifteen minutes before ventilation, the rats received intravenous APC (250 µg/kg, HVZP+APC group) or normal saline (vehicle; HVZP group). Another group that received no ventilation served as the control group. Results: Levels of arterial blood gas tension were comparable between the two ventilation groups throughout the study period. Rats treated with the HVZP protocol exhibited significantly higher total protein and macrophage inflammatory protein-2 concentrations in bronchoalveolar lavage fluid (BALF) and higher lung PAI-1 mRNA expression and plasma active PAI-1 levels than did the control group. Administration of APC tended to reduce the BALF protein content and systemic PAI-1 activity but did not improve the lung histology in the HVZP+APC group. Plasma levels of D-dimers were comparable among the three study groups. Conclusions: These results suggest that APC administered at a higher dosage might improve lung function by reducing alveolar protein leakage and systemic coagulation.
Bromocriptine and Dopamine Mediate Independent and Synergistic Apoptotic Pathways in Pituitary Cells
Authors: Rowther F.B. , Richardson A. , Clayton R.N. , Farrell W.E.
Published: January 2010

Dopamine (DA) agonists are the primary treatment choice for prolactinoma, effectively suppressing prolactin expression and reducing tumour size. However, the intracellular pathway(s) through which either DA or its agonists impact on proliferation or lead to tumour shrinkage are incompletely understood. To identify the mediators in the apoptotic cascades after DA or DA agonist challenges we used a well-characterized model system, the rodent somatolactotroph cell line GH3. In these cells, we show that apoptosis induced by the DA agonist bromocriptine (BC), but not DA, is initiated through activation of the JNK pathway. However, both DA and BC activate the terminal effector caspase, caspase-3. Kinetic studies and chemical inhibitor co-incubation experiments support a role for JNK activation preceding caspase-9 activation in BC challenged cells, however, engagement of these mediators was not apparent in DA challenge cells. These studies suggest that apoptosis induced by BC or DA is mediated through distinct and independent pathways that converge with activation of the terminal caspase, caspase-3. These observations were further reinforced by our findings that DA and BC, in co-incubation experiments, synergistically induce apoptosis. These findings raise the possibility that drugs acting through the same pathway as DA may be clinically beneficial when combined with BC.
Tissue-Specific Liver X Receptor Activation Promotes Macrophage Reverse Cholesterol Transport In Vivo
Authors: Yasuda Tomoyuki , Grillot Didier , Billheimer Jeffery T. , Briand François , Delerive Philippe , Huet Stephane , Rader Daniel J.
Published: January 2010

Objective—

We previously reported that a systemic liver X receptor (LXR) agonist promoted macrophage reverse-cholesterol transport (mRCT) in vivo. Because LXR are expressed in multiple tissues involved in RCT (macrophages, liver, intestine), we analyzed the effect of tissue-specific LXR agonism on mRCT.

Methods and Results—

In initial studies, the systemic LXR agonist GW3965 failed to promote mRCT in a setting in which LXR was expressed in macrophages but not in liver or intestine. To evaluate the effect of LXR activation specifically in small intestine on mRCT, wild-type mice were treated with either intestinal-specific LXR agonist (GW6340) or systemic LXR agonist (GW3965). Both GW3965 and GW6340 significantly promoted excretion of [
3
H]-sterol in feces by 162% and 52%, respectively. To evaluate the requirement for macrophage LXR activation, we assessed the ability of GW3965 to promote mRCT in wild-type mice using primary macrophages deficient in LXRα/β vs wild-type macrophages. Whereas GW3965 treatment promoted fecal excretion compared with vehicle, its overall ability to promote mRCT was significantly attenuated using LXRα/β knockout macrophages.

Conclusion—

We demonstrate that intestinal-specific LXR agonism promotes macrophage RCT in vivo and that macrophage LXR itself plays an important, but not predominant, role in promoting RCT in response to an LXR agonist.
Nonenzymatic Glycation Impairs the Antiinflammatory Properties of Apolipoprotein A-I
Authors: Nobécourt Estelle , Tabet Fatiha , Lambert Gilles , Puranik Rajesh , Bao Shisan , Yan Ling , Davies Michael J. , Brown Bronwyn E. , Jenkins Alicia J. , Dusting Gregory J. , Bonnet David J. , Curtiss Linda K. , Barter Philip J. , Rye Kerry-Anne
Published: January 2010

Objective—

The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I.

Methods and Results—

Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I

N

), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I

Glyc in vitro

), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I

Glyc in vivo

), discoidal reconstituted high-density lipoproteins (rHDL) containing phosphatidylcholine and apoA-I

N

, (A-I

N

)rHDL, or apoA-I

Glyc in vitro

, (A-I

Glyc in vitro

)rHDL. At 24 hours postinfusion, acute vascular inflammation was induced by inserting a nonocclusive, periarterial carotid collar. The animals were euthanized 24 hours after the insertion of the collar. The collars caused intima/media neutrophil infiltration and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). ApoA-I

N

infusion decreased neutrophil infiltration and VCAM-1 and ICAM-1 expression by 89%, 90%, and 66%, respectively. The apoA-I

Glyc in vitro

infusion decreased neutrophil infiltration by 53% but did not reduce VCAM-1 or ICAM-1 expression. ApoA-I

Glyc in vivo

did not inhibit neutrophil infiltration or adhesion molecule expression. (A-I

Glyc in vitro

)rHDL also inhibited vascular inflammation less effectively than (A-I

N

)rHDL. The reduced antiinflammatory properties of nonenzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-κB activation and reactive oxygen species formation.

Conclusion—

Nonenzymatic glycation impairs the antiinflammatory properties of apoA-I.
Dynamic Changes in Lung MicroRNA Profiles During the Development of Pulmonary Hypertension due to Chronic Hypoxia and Monocrotaline
Authors: Caruso Paola , MacLean Margaret R. , Khanin Raya , McClure John , Soon Elaine , Southgate Mark , MacDonald Robert A. , Greig Jenny A. , Robertson Keith E. , Masson Rachel , Denby Laura , Dempsie Yvonne , Long Lu , Morrell Nicholas W. , Baker Andrew H.
Published: January 2010

Objective—

MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding “seed” sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds of genes. The regulation of miRNAs in the lung during the development of pulmonary arterial hypertension (PAH) is unknown.

Methods and Results—

We screened lung miRNA profiles in a longitudinal and crossover design during the development of PAH caused by chronic hypoxia or monocrotaline in rats. We identified reduced expression of Dicer, involved in miRNA processing, during the onset of PAH after hypoxia. MiR-22, miR-30, and let-7f were downregulated, whereas miR-322 and miR-451 were upregulated significantly during the development of PAH in both models. Differences were observed between monocrotaline and chronic hypoxia. For example, miR-21 and let-7a were significantly reduced only in monocrotaline-treated rats. MiRNAs that were significantly regulated were validated by quantitative polymerase chain reaction. By using in vitro studies, we demonstrated that hypoxia and growth factors implicated in PAH induced similar changes in miRNA expression. Furthermore, we confirmed miR-21 downregulation in human lung tissue and serum from patients with idiopathic PAH.

Conclusion—

Defined miRNAs are regulated during the development of PAH in rats. Therefore, miRNAs may contribute to the pathogenesis of PAH and represent a novel opportunity for therapeutic intervention.
Decreased Levels of Embryonic Retinoic Acid Synthesis Accelerate Recovery From Arterial Growth Delay in a Mouse Model of DiGeorge Syndrome
Authors: Ryckebüsch Lucile , Bertrand Nicolas , Mesbah Karim , Bajolle Fanny , Niederreither Karen , Kelly Robert G. , Zaffran Stéphane
Published: January 2010

Rationale
:

Loss of
Tbx1
and decrease of retinoic acid (RA) synthesis result in DiGeorge/velocardiofacial syndrome (DGS/VCFS)-like phenotypes in mouse models, including defects in septation of the outflow tract of the heart and anomalies of pharyngeal arch-derived structures including arteries of the head and neck, laryngeal-tracheal cartilage, and thymus/parathyroid. Wild-type levels of T-box transcription factor (Tbx)1 and RA signaling are required for normal pharyngeal arch artery development. Recent studies have shown that reduction of RA or loss of
Tbx1
alters the contribution of second heart field (SHF) progenitor cells to the elongating heart tube.

Objective
:

Here we tested whether Tbx1 and the RA signaling pathway interact during the deployment of the SHF and formation of the mature aortic arch.

Methods and Results
:

Molecular markers of the SHF, neural crest and smooth muscle cells, were analyzed in
Raldh2
;
Tbx1
compound heterozygous mutants. Our results revealed that the SHF and outflow tract develop normally in
Raldh2
+/−
;
Tbx1
+/−
embryos. However, we found that decreased levels of RA accelerate the recovery from arterial growth delay observed in
Tbx1
+/−
mutant embryos. This compensation coincides with the differentiation of smooth muscle cells in the 4th pharyngeal arch arteries, and is associated with severity of neural crest cell migration defects observed in these mutants.

Conclusions
:

Our data suggest that differences in levels of embryonic RA may contribute to the variability in great artery anomalies observed in DGS/VCFS patients.
Relative Roles of Direct Regeneration Versus Paracrine Effects of Human Cardiosphere-Derived Cells Transplanted Into Infarcted Mice
Authors: Chimenti Isotta , Smith Rachel Ruckdeschel , Li Tao-Sheng , Gerstenblith Gary , Messina Elisa , Giacomello Alessandro , Marbán Eduardo
Published: January 2010

Rationale:

Multiple biological mechanisms contribute to the efficacy of cardiac cell therapy. Most prominent among these are direct heart muscle and blood vessel regeneration from transplanted cells, as opposed to paracrine enhancement of tissue preservation and/or recruitment of endogenous repair.

Objective:

Human cardiac progenitor cells, cultured as cardiospheres (CSps) or as CSp-derived cells (CDCs), have been shown to be capable of direct cardiac regeneration in vivo. Here we characterized paracrine effects in CDC transplantation and investigated their relative importance versus direct differentiation of surviving transplanted cells.

Methods and Results:

In vitro, many growth factors were found in media conditioned by human adult CSps and CDCs; CDC-conditioned media exerted antiapoptotic effects on neonatal rat ventricular myocytes, and proangiogenic effects on human umbilical vein endothelial cells. In vivo, human CDCs secreted vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor 1 when transplanted into the same SCID mouse model of acute myocardial infarction where they were previously shown to improve function and to produce tissue regeneration. Injection of CDCs in the peri-infarct zone increased the expression of Akt, decreased apoptotic rate and caspase 3 level, and increased capillary density, indicating overall higher tissue resilience. Based on the number of human-specific cells relative to overall increases in capillary density and myocardial viability, direct differentiation quantitatively accounted for 20% to 50% of the observed effects.

Conclusions:

Together with their spontaneous commitment to cardiac and angiogenic differentiation, transplanted CDCs serve as “role models,” recruiting endogenous regeneration and improving tissue resistance to ischemic stress. The contribution of the role model effect rivals or exceeds that of direct regeneration.
Social Class, School and Non-School Environments, and Black/White Inequalities in Children's Learning
Authors: Condron Dennis J.
Published: January 2010

As social and economic stratification between black and white Americans persists at the dawn of the twenty-first century, disparities in educational outcomes remain an especially formidable barrier. Recent research on the black/white achievement gap points to a perplexing pattern in this regard. Schools appear to exacerbate black/white disparities in learning while simultaneously slowing the growth of social class gaps. How might this occur? Using 1st grade data from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), I test—and find support for—the proposition that school factors play an elevated role in generating the black/white achievement gap while non-school factors primarily drive social class inequalities. These findings help explain why black/white achievement disparities grow mostly during the school year (when schools are in session and have their greatest impact on students' learning) while class gaps widen mostly during the summer (when school is out of session and non-school influences dominate). I conclude by discussing the implications for future research, especially as they pertain to what appears to be the most important contributor to the black/white achievement gap: school racial segregation.
Residential Segregation and Birth Weight among Racial and Ethnic Minorities in the United States
Authors: Walton Emily
Published: January 2010

Racial and ethnic minorities are often residentially segregated from whites in urban settings, a fact which has important health consequences. Research on the relationship between residential segregation and health outcomes lacks national-level investigation of racial and ethnic minority groups other than African Americans. I use multilevel analyses to examine the associations of residential isolation and clustering with birth weight among Asian, black, and Latino Americans using data from the National Center for Health Statistics' Natality Files and the U.S. Census. Findings indicate that segregation has a negative effect on the likelihood of having a low birth weight baby among Asian Americans, suggesting a possible concentration of social and structural resources in highly-segregated communities. On the contrary, segregation marginally increases the odds of low birth weight among African Americans, but only in the presence of higher poverty rates. Segregation does not affect birth weight among Latino Americans.
Comparison of Bending, Drapability and Crease Recovery Behaviors of Woven Fabrics Produced from Polyester Fibers Having Different Cross-sectional Shapes
Authors: Omeroglu S. , Karaca E. , Becerir B.
Published: January 2010

In this paper, full and hollow fibers having round and trilobal cross-sectional shapes were produced in equal manufacturing conditions and bending, drapability and crease recovery behaviors of the woven fabrics produced from these fibers were investigated. The bending rigidities of the fabrics produced from hollow fibers were higher than the bending rigidities of the fabrics produced from full fibers. The highest bending rigidities were obtained in fabrics produced from hollow round fibers. The bending rigidities and drapabilities of the fabrics produced from fibers of similar cross-sectional shapes were in close relation with each other. The fabrics produced from full fibers had higher drapabilities than those produced from hollow fibers. The fabrics produced from full fibers had higher crease recovery angles than those produced from hollow fibers. Considering that the construction properties of the fabrics were kept constant, it could be concluded that the differences among the properties of the fabrics which were produced from full and hollow fibers (for both round and trilobal cross-sectional shapes) basically emerged from the very high differences between moments of inertia of full and hollow cross sections. It was also considered that another factor which caused differences between the fabric properties was the different bulkiness of the fibers and also the different bulkiness of the yarns with the same counts. The best results could be obtained with round and trilobal full fibers at fabrics in which drapability and crease recovery are desired.
Staying Out of Trouble: Intentions of Young Male Offenders
Authors: Forste Renata , Clarke Lynda , Bahr Stephen
Published: January 2010

During the fall of 2005, we interviewed a sample of 103 young men aged 18 to 21 imprisoned at a young offender’s prison in England. Drawing on the theory of planned behavior, as well as the theory of cognitive transformation, our purpose was to investigate prisoners’ reports of their likelihood of reoffending following release from prison. Primary explanatory factors included measures of attitudes, behavioral control, and subjective norms. Attitudes measured inmates’ plans of what they would do following release. Behavioral control variables included indicators of life control and self-efficacy. Subjective norms measured the number of peers inmates reported ever being imprisoned. Prison activities and background characteristics were also modeled. The data were analyzed using regression techniques and structural equation modeling. Intentions to stay out of trouble were most strongly associated with self-efficacy and the number of imprisoned friends reported. Intentions were also associated with the specificity of postrelease plans and life control. Offenders’ feelings of life control were stronger among those who had more frequent contact with family members and friends while in prison. Employment prior to prison and family relationships were predictive of contacts with family and friends in prison. Specific policies consistent with our findings include encouragement of contact with family members and friends. In addition, interventions that help offenders make specific plans and increase feelings of control and self-efficacy have promise in helping released offenders successfully complete the transition from prison to the community.
Cartographic calculations of territory
Authors: Crampton Jeremy W.
Published: January 2010

Two themes dominate this year’s report: calculation and territory. Both of these are larger issues than cartography itself, but cartography has been increasingly drawn into their ambit such that we might tentatively identify cartographic calculations of territory. Ranging across a wide set of problems including colonial, political and racial mappings, not to mention indigeneity and philosophical concerns of ontology, calculation and territory mark out a wide swath of cartographically informed work.
The Effects of Helical Ribs’ Number and Grid Types on the Buckling of Thin-walled GFRP-stiffened Shells under Axial Loading
Authors: Yazdani M. , Rahimi G.H.
Published: January 2010

The results of an experimental study on the buckling behavior of thin-walled GFRP-stiffened cylindrical shells are presented. The buckling behavior of stiffened shells, with lozenge and triangular grids, and unstiffened shells were studied under quasi-static axial loading at room temperature. The effect of the number of helical ribs and grid shapes was thoroughly investigated. During the experimental study, local skin buckling mode was observed on all specimens. Based on the findings from this work, a minimum number of stiffeners should be present in a structure in order to play an effective role in its strength. Furthermore, it was concluded that under axial loading, increasing the number of helical ribs is more effective than adding hoop rings and changing the grid types.
An Investigation of Dielectric Properties of Chicken Feather Reinforced Epoxy Matrix Composite
Authors: Mishra S.C. , Nayak Nadiya Bihary
Published: January 2010

The present investigation aims at developing a reinforced polymer composite to be used in electronic applications (for/as high-speed data transforming insulator material). Poultry feather reinforced composite is prepared varying the reinforcement of chicken feather fibrils (i.e., with 10%, 20%, and 30% weight fraction) using epoxy resin as matrix material. The dielectric properties of the composites are evaluated at different temperature and frequency ranges. It is found that the dielectric properties are dependent on operating frequency and temperature conditions. Such composites have potential use as a low dielectric material for typical applications. Flexural strength, microhardness, and density of this chicken feather composite are also evaluated. Microscopic observation of the feather is made with scanning electron microscope.
Experimental Investigation of Relaxation of Fiber-reinforced Polymer Composites
Authors: Oskouei Asghar Vatani , Taleie Shahab Mehdizad
Published: January 2010

This article presents the results of experimental investigation of FRP relaxations in pre-stressing methods. Test variables were the type of fibers, the level of pre-stressing, and the size and shape of fibers. The main goal of this research is to describe relaxation of fiber-reinforced polymer-based material and time. Test results showed that the relaxation of FRP materials include fiber relaxation, resin relaxation, and microscopic tearing of fibers. Test results also show that the relaxation of AFRP materials is higher than that of CFRP and GFRP.
A Review of Family-Based Programs to Prevent Youth Violence Among Latinos
Authors: Leidy Melinda S. , Guerra Nancy G. , Toro Rosa I.
Published: January 2010

At present, there is limited evidence supporting the effectiveness of family-based intervention programs to prevent violence or related behavior problems with Latino youth and families. Although progress has been made, a number of important issues remain. In this article, the authors review several of the more prominent interventions for Latino youth and families, highlighting how they were adapted to or developed for Latino culture. They begin by discussing cultural sensitivity and how it affects the design, implementation, and adaptation of youth violence prevention programs. Following this, the authors review and discuss programs adapted for Latino families followed by programs developed specifically for Latino families. They highlight four primary components of family-based programs that have been linked most frequently to prevention outcomes: (a) improving parental monitoring, (b) increasing family cohesion, (c) increasing networking across families, and (d) empowering families to access resources more effectively.