bluuebunny/crossref_metadata_2025 huggingface dataset:
Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
Authors: Zhang Lei , Riepler Sabrina J. , Turner Nigel , Enriquez Ronaldo F. , Lee I-Chieh J. , Baldock Paul A. , Herzog Herbert , Sainsbury Amanda
Published: September 2010

Neuropeptide Y receptors are critical regulators of energy homeostasis and are well known for their powerful influence on feeding, but their roles in other important aspects of energy homeostasis, such as energy expenditure and their functional interactions in these processes, are largely unknown. Here we show that mice lacking both Y2 and Y4 receptors exhibited a reduction in adiposity, more prominent in intra-abdominal vs. subcutaneous fat, and an increase in lean mass as determined by dual-energy X-ray absorptiometry. These changes were more pronounced than those seen in mice with Y2 or Y4 receptor single deletion, demonstrating the important roles and synergy of Y2 and Y4 signaling in the regulation of body composition. These changes in body composition occurred without significant changes in food intake, but energy expenditure and physical activity were significantly increased in Y4−/− and particularly in Y2−/−Y4−/− but not in Y2−/− mice, suggesting a critical role of Y4 signaling and synergistic interactions with Y2 signaling in the regulation of energy expenditure and physical activity. Y2−/− and Y4−/− mice also exhibited a decrease in respiratory exchange ratio with no further synergistic decrease in Y2−/−Y4−/− mice, suggesting that Y2 and Y4 signaling each play important and independent roles in the regulation of substrate utilization. The synergy between Y2 and Y4 signaling in regulating fat mass may be related to differences in mitochondrial oxidative capacity, since Y2−/−Y4−/− but not Y2−/− or Y4−/− mice showed significant increases in muscle protein levels of peroxisome proliferator-activated receptor (PPAR)γ coactivator (PGC)-1α, and mitochondrial respiratory chain complexes I and III. Taken together, this work demonstrates the critical roles of Y2 and Y4 receptors in the regulation of body composition and energy metabolism, highlighting dual antagonism of Y2 and Y4 receptors as a potentially effective anti-obesity treatment.
Visuomotor Learning Generalizes Between Bilateral and Unilateral Conditions Despite Varying Degrees of Bilateral Interference
Authors: Wang Jinsung , Mordkoff J. Toby , Sainburg Robert L.
Published: September 2010

Bilateral interference, referring to the tendency of movements of one arm to disrupt the intended movements made simultaneously with the other arm, is often observed in a task that involves differential planning of each arm movement during sensorimotor adaptation. In the present study, we examined two questions: 1) how does the compatibility between visuomotor adaptation tasks performed with both arms affect bilateral interference during bimanual performance? and 2) how do variations in bilateral interference affect transfer of visuomotor adaptation between bilateral and unilateral conditions? To examine these questions, we manipulated visuomotor compatibility using two kinematic variables (direction of required hand motion, direction of an imposed visual rotation). Experiment 1 consisted of two conditions in which the direction of visual rotations for both arms was either in the same or opposing directions, whereas the target direction for both arms was always the same. In experiment 2, we examined the pattern of generalization between the bilateral and unilateral conditions when both the target and rotation directions were opposing between the arms. In both experiments, subjects first adapted to a 30° visual rotation with one arm (preunilateral), then with both arms (bilateral), and finally with the arm that was not used in the first session (postunilateral). Our results show that bilateral interference was smallest when both variables were the same between the arms. Our data also show extensive transfer of visuomotor adaptation between bilateral and unilateral conditions, regardless of degree of bilateral interference.
Linear Hypergeneralization of Learned Dynamics Across Movement Speeds Reveals Anisotropic, Gain-Encoding Primitives for Motor Adaptation
Authors: Joiner Wilsaan M. , Ajayi Obafunso , Sing Gary C. , Smith Maurice A.
Published: September 2010

The ability to generalize learned motor actions to new contexts is a key feature of the motor system. For example, the ability to ride a bicycle or swing a racket is often first developed at lower speeds and later applied to faster velocities. A number of previous studies have examined the generalization of motor adaptation across movement directions and found that the learned adaptation decays in a pattern consistent with the existence of motor primitives that display narrow Gaussian tuning. However, few studies have examined the generalization of motor adaptation across movement speeds. Following adaptation to linear velocity-dependent dynamics during point-to-point reaching arm movements at one speed, we tested the ability of subjects to transfer this adaptation to short-duration higher-speed movements aimed at the same target. We found near-perfect linear extrapolation of the trained adaptation with respect to both the magnitude and the time course of the velocity profiles associated with the high-speed movements: a 69% increase in movement speed corresponded to a 74% extrapolation of the trained adaptation. The close match between the increase in movement speed and the corresponding increase in adaptation beyond what was trained indicates linear hypergeneralization. Computational modeling shows that this pattern of linear hypergeneralization across movement speeds is not compatible with previous models of adaptation in which motor primitives display isotropic Gaussian tuning of motor output around their preferred velocities. Instead, we show that this generalization pattern indicates that the primitives involved in the adaptation to viscous dynamics display anisotropic tuning in velocity space and encode the gain between motor output and motion state rather than motor output itself.
Actions and interactions of progesterone and estrogen on transcriptome profiles of the bovine endometrium
Authors: Shimizu Takashi , Krebs Stefan , Bauersachs Stefan , Blum Helmut , Wolf Eckhard , Miyamoto Akio
Published: September 2010

The aim of our study was to analyze endometrial gene expression profiles in ovariectomized cows treated with estradiol and/or progesterone by using microarray analysis. Clustering of differentially expressed genes allowed separation into distinct hormone response patterns. These patterns could be classified into independent and interdependent actions of the steroid hormones estrogen and progesterone. The use of ovariectomized cows and external administration of hormones identified a set of genes whose regulation depends on a progesterone priming effect. The progesterone-primed estrogen response comprises gene functions such as migration, cell differentiation, and cell adhesion and therefore may play a crucial role in tissue remodeling, as one of its key regulators in the endometrium, TGFB2, is among this group of progesterone-primed genes. Functional annotation analysis of the estrogen-responsive gene clusters shows a clear dominance of functions such as cell cycle, morphogenesis, and differentiation. The functional profile of the progesterone-responsive clusters is less clear but nevertheless shows some important fertility-related terms like luteinization, oocyte maturation, and catecholamine metabolism. We looked for putative regulators of the steroid hormone response in endometrium by searching for enriched transcription factor binding sites in the promoter regions of the genes with similar hormone response profile. This analysis identified transcription factors such as SP1, NFYA, FOXA2, IRF2, ESR1, and NOBOX as candidate regulators of gene expression in bovine endometrium treated with steroid hormones. Taken together, our data provide novel insights into the regulation of bovine endometrial physiology by steroid hormones.
De novo Lipogenesis Protects Cancer Cells from Free Radicals and Chemotherapeutics by Promoting Membrane Lipid Saturation
Authors: Rysman Evelien , Brusselmans Koen , Scheys Katryn , Timmermans Leen , Derua Rita , Munck Sebastian , Van Veldhoven Paul P. , Waltregny David , Daniëls Veerle W. , Machiels Jelle , Vanderhoydonc Frank , Smans Karine , Waelkens Etienne , Verhoeven Guido , Swinnen Johannes V.
Published: September 2010

Activation of de novo lipogenesis in cancer cells is increasingly recognized as a hallmark of aggressive cancers and has been implicated in the production of membranes for rapid cell proliferation. In the current report, we provide evidence that this activation has a more profound role. Using a mass spectrometry–based phospholipid analysis approach, we show that clinical tumor tissues that display the lipogenic phenotype show an increase in the degree of lipid saturation compared with nonlipogenic tumors. Reversal of the lipogenic switch in cancer cells by treatment with the lipogenesis inhibitor soraphen A or by targeting lipogenic enzymes with small interfering RNA leads to a marked decrease in saturated and mono-unsaturated phospholipid species and increases the relative degree of polyunsaturation. Because polyunsaturated acyl chains are more susceptible to peroxidation, inhibition of lipogenesis increases the levels of peroxidation end products and renders cells more susceptible to oxidative stress–induced cell death. As saturated lipids pack more densely, modulation of lipogenesis also alters lateral and transversal membrane dynamics as revealed by diffusion of membrane-targeted green fluorescent protein and by the uptake and response to doxorubicin. These data show that shifting lipid acquisition from lipid uptake toward de novo lipogenesis dramatically changes membrane properties and protects cells from both endogenous and exogenous insults. These findings provide important new insights into the role of de novo lipogenesis in cancer cells, and they provide a rationale for the use of lipogenesis inhibitors as antineoplastic agents and as chemotherapeutic sensitizers. Cancer Res; 70(20); 8117–26. ©2010 AACR.
Glucuronidation Genotypes and Nicotine Metabolic Phenotypes: Importance of Functional UGT2B10 and UGT2B17 Polymorphisms
Authors: Chen Gang , Giambrone Nino E. , Dluzen Douglas F. , Muscat Joshua E. , Berg Arthur , Gallagher Carla J. , Lazarus Philip
Published: September 2010

Glucuronidation is an important pathway in the metabolism of nicotine, with previous studies suggesting that ∼22% of urinary nicotine metabolites are in the form of glucuronidated compounds. Recent in vitro studies have suggested that the UDP-glucuronosyltransferases (UGT) 2B10 and 2B17 play major roles in nicotine glucuronidation with polymorphisms in both enzymes shown to significantly alter the levels of nicotine-glucuronide, cotinine-glucuronide, and trans-3′-hydroxycotinine (3HC)–glucuronide in human liver microsomes in vitro. In the present study, the relationship between the levels of urinary nicotine metabolites and functional polymorphisms in UGTs 2B10 and 2B17 was analyzed in urine specimens from 104 Caucasian smokers. Based on their percentage of total urinary nicotine metabolites, the levels of nicotine-glucuronide and cotinine-glucuronide were 42% (P < 0.0005) and 48% (P < 0.0001), respectively, lower in the urine from smokers exhibiting the UGT2B10 (*1/*2) genotype and 95% (P < 0.05) and 98% (P < 0.05), respectively, lower in the urine from smokers with the UGT2B10 (*2/*2) genotype compared with the urinary levels in smokers having the wild-type UGT2B10 (*1/*1) genotype. The level of 3HC-glucuronide was 42% (P < 0.001) lower in the urine from smokers exhibiting the homozygous UGT2B17 (*2/*2) deletion genotype compared with the levels in urine from wild-type UGT2B17 subjects. These data suggest that UGTs 2B10 and 2B17 play important roles in the glucuronidation of nicotine, cotinine, and 3HC and suggest that the UGT2B10 codon 67 SNP and the UGT2B17 gene deletion significantly reduce overall glucuronidation rates of nicotine and its major metabolites in smokers. Cancer Res; 70(19); 7543–52. ©2010 AACR.
RasGRP3 Contributes to Formation and Maintenance of the Prostate Cancer Phenotype
Authors: Yang Dazhi , Kedei Noemi , Li Luowei , Tao Juan , Velasquez Julia F. , Michalowski Aleksandra M. , Tóth Balázs I. , Marincsák Rita , Varga Attila , Bíró Tamás , Yuspa Stuart H. , Blumberg Peter M.
Published: September 2010

RasGRP3 mediates the activation of the Ras signaling pathway that is present in many human cancers. Here, we explored the involvement of RasGRP3 in the formation and maintenance of the prostate cancer phenotype. RasGRP3 expression was elevated in multiple human prostate tumor tissue samples and in the human androgen-independent prostate cancer cell lines PC-3 and DU 145 compared with the androgen-dependent prostate cancer cell line LNCaP. Downregulation of endogenous RasGRP3 in PC-3 and DU 145 cells reduced Ras-GTP formation, inhibited cell proliferation, impeded cell migration, and induced apoptosis. Anchorage-independent growth of the PC-3 cells and tumor formation in mouse xenografts of both cell lines were likewise inhibited. Inhibition of RasGRP3 expression reduced AKT and extracellular signal-regulated kinase 1/2 phosphorylation and sensitized the cells to killing by carboplatin. Conversely, exogenous RasGRP3 elevated Ras-GTP, stimulated proliferation, and provided resistance to phorbol 12-myristate 13-acetate–induced apoptosis in LNCaP cells. RasGRP3-overexpressing LNCaP cells displayed a markedly enhanced rate of xenograft tumor formation in both male and female mice compared with the parental line. Suppression of RasGRP3 expression in these cells inhibited downstream RasGRP3 responses, caused the cells to resume the LNCaP morphology, and suppressed growth, confirming the functional role of RasGRP3 in the altered behavior of these cells. We conclude that RasGRP3 contributes to the malignant phenotype of the prostate cancer cells and may constitute a novel therapeutic target for human prostate cancer. Cancer Res; 70(20); 7905–17. ©2010 AACR.
Rapamycin Regulates Stearoyl CoA Desaturase 1 Expression in Breast Cancer
Authors: Luyimbazi David , Akcakanat Argun , McAuliffe Priscilla F. , Zhang Li , Singh Gopal , Gonzalez-Angulo Ana Maria , Chen Huiqin , Do Kim-Anh , Zheng Yuhuan , Hung Mien-Chie , Mills Gordon B. , Meric-Bernstam Funda
Published: September 2010

Mammalian target of rapamycin (mTOR) signaling is a central regulator of protein translation, cell growth, and metabolism. Alterations of the mTOR signaling pathway are common in cancer, making mTOR a promising therapeutic target. In clinical trials, rapamycin analogs have shown modest response rates for most cancer types, including breast cancer. Therefore, there is an urgent need to better understand the mechanism of action of rapamycin to improve patient selection and to monitor pathway inhibition. To identify novel pharmacodynamic markers of rapamycin activity, we carried out transcriptional profiling of total and polysome-associated RNA in three breast cancer cell lines representing different subtypes. In all three cell lines, we found that rapamycin significantly decreased polysome-associated mRNA for stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis. Activators of mTOR increased SCD1 protein expression, whereas rapamycin, LY294002, and BEZ235 decreased SCD1 protein expression. Rapamycin decreased total SCD1 RNA expression without inducing a significant decline in its relative polysomal recruitment (polysome/total ratio). Rapamycin did not alter SCD1 mRNA stability. Instead, rapamycin inhibited SCD1 promoter activity and decreased expression of mature transcription factor sterol regulatory element binding protein 1 (SREBP1). Eukaryotic initiation factor 4E (eIF4E) small interfering RNA (siRNA) decreased both SCD1 and SREBP1 expression, suggesting that SCD1 may be regulated through the mTOR/eIF4E-binding protein 1 axis. Furthermore, SCD1 siRNA knockdown inhibited breast cancer cell growth, whereas overexpression increased growth. Taken together these findings show that rapamycin decreases SCD1 expression, establishing an important link between cell signaling and cancer cell fatty acid synthesis and growth. Mol Cancer Ther; 9(10); 2770–84. ©2010 AACR.
Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on the Long-Term Outcome after Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation
Authors: Klemm Hanno U. , Heitzer Thomas , Ruprecht Ute , Meinertz Thomas , Ventura Rodolfo
Published: September 2010

Objectives: The effect of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) on the long-term outcome after pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) is unknown. Methods: This matched-pair study included 102 patients with PAF treated with ACE-I or ARBs (group 1) and 102 control subjects (group 2) after standardized PVI. Tele-ECG recorders were used to detect the end point of the first PAF recurrence after a 3-month blanking period. Results: Median follow-up was 2.1 years (range 0.3–6.3). In group 1, 51 (50%) patients suffered recurrences, with a mean time to recurrence of 3.2 years (95% CI 2.6–3.8). In group 2, 67 (65.7%) patients presented PAF after a mean period of 2.2 years (95% CI 1.7–2.8; p = 0.009). A second ablation was performed in 31 (50%) patients from the treatment group and in 48 (66.7%) patients from the control group (p = 0.02). Multivariate Cox analysis showed treatment with ACE-I and ARBs to be the only significant predictor of a reduced recurrence rate (HR 0.49, 95% CI 0.32–0.75). Conclusion: ACE-I and ARBs were effective for the preservation of sinus rhythm after PAF ablation, and they reduced the reablation rate.
Homocysteine Levels in Patients with Heart Failure with Preserved Ejection Fraction
Authors: Okuyan Ertuğrul , Uslu Ahmet , Çakar Mehmet Akif , Sahin Irfan , Önür Imran , Enhos Asım , Biter Halil Ibrahim , Çetin Şükrü , Dinçkal Mustafa Hakan
Published: September 2010

Objectives: Increased homocysteine (HCY) levels are associated with an increased risk of cardiovascular disease. Plasma HCY is increased in chronic heart failure (CHF) patients, and previous studies suggest that hyperhomocysteinemia causes adverse cardiac remodeling and affects pump function. We aimed to evaluate the HCY levels in patients with diastolic heart failure with preserved left ventricular ejection fraction (LVEF). Methods: We prospectively studied 68 patients (39 females and 29 males) who were hospitalized for symptomatic heart failure, as well as 40 age- and sex-matched healthy subjects who comprised the control group. CHF was diagnosed in all cases based on Framingham diagnostic criteria. CHF with preserved LVEF was defined as cases with CHF with an LVEF of 50% or more. Patients with regional left ventricular wall motion abnormalities, atrial fibrillation, and renal failure were excluded. Results: The mean age was 65.5 ± 9.6 years in the heart failure group and 65.2 ± 9.7 years in the control group. The mean LVEF was 59.8 ± 5.3 in the heart failure group and 61.4 ± 5.2 in the control group. The mean total fasting HCY concentrations were significantly higher in patients with heart failure (16.9 ± 5.27 µmol/l vs. 10.15 ± 3.49 µmol/l, respectively; p < 0.001). Multiple regression analysis indicated that NT-proBNP, hs-CRP, E/A ratio, and HbA1C were independently associated with hyperhomocysteinemia. Conclusions: Our results suggest that hyperhomocysteinemia is prevalent in heart failure with preserved ejection fraction. Larger scale studies are needed to clarify its pathogenic mechanisms and effects on the natural history of heart failure.
Etiology and Antibiotic Susceptibility Patterns of Community- and Hospital-Acquired Urinary Tract Infections in a General Hospital in Kuwait
Authors: Al Benwan Khalifa , Al Sweih Noura , Rotimi Vincent O.
Published: September 2010

Objective: Our purpose was to determine the bacterial profile and prevalence of antibiotic resistance patterns of uropathogens, as well as evaluate the problem with extended-spectrum β-lactamase (ESBL) producing isolates, causing urinary tract infections (UTIs) in Al-Amiri Hospital, Kuwait, over a 3-year period. Materials and Methods: Isolates (56,505) from symptomatic UTI cases from January 2005 to December 2007 were identified by conventional methods and the VITEK identification card system. Antimicrobial susceptibility testing was performed by disk diffusion method for Gram-positive organisms and an automated VITEK 2 machine for Gram-negative organisms. ESBL production by the Enterobacteriaceae was detected by the double-disk diffusion method and VITEK-2 system. Results: Significant bacteriuria was detected in 15,064 (26.6%) of the 56,505 urine samples. Escherichia coli accounted for 4,876 (54.9%) from community-acquired UTI (CA-UTI) and 2,253 (36.4%) from hospital-acquired UTI (HA-UTI), followed by Streptococcus agalactiae (1,129, 12.7%) and Klebsiella pneumoniae (962, 10.8%) from CA-UTI cases. Candida spp. (973, 15.7%) and K. pneumoniae (747, 12.1%) were the second and third most prevalent isolates, respectively, in HA-UTI. High resistance rates were observed among the Enterobacteriaceae against ampicillin, cephalothin, ciprofloxacin, piperacillin and trimethoprim-sulfamethoxazole. About 855 (12%) and 291 (17%) of E. coli and K. pneumoniae, respectively, were resistant to ≧4 antibiotics. The prevalence of ESBL-producing E. coli and K. pneumoniae in CA-UTI was 12 and 17% and in HA-UTI 26 and 28%, respectively. Conclusion: A high percentage of the uropathogens causing UTI in the Al-Amiri Hospital setting was highly resistant to the first- and second-line antibiotics for the therapy of UTI. ESBL-producing bacteria are highly prevalent in our hospital.
Calpain-10 Gene Polymorphism in Type 2 Diabetes Mellitus Patients in the Gaza Strip
Authors: Zaharna Mazen M. , Abed Abdalla A. , Sharif Fadel A.
Published: September 2010

Objective: To examine the role of calpain-10 SNP-44, -43, -63 and del/ins-19 in genetic susceptibility to type 2 diabetes mellitus (T2DM) and associations with triglycerides and total cholesterol in a group of subjects residing in the Gaza Strip. Subjects and Methods: Ninety-six individuals were examined: 48 T2DM patients and 48 controls. The groups were genotyped for calpain-10 SNP-44, -43, -63, and del/ins-19. Mutagenically separated polymerase chain reaction was used to examine SNP-44; del/ins-19 was examined by electrophoresis of the PCR product on agarose gel, while the restriction fragment length polymorphism method was used for SNP-43 and -63. Results: There was evidence that the C allele at SNP-44 played a possible role in susceptibility to T2DM (p = 0.01). T2DM patients with G/A genotype were found to have higher levels of total cholesterol in comparison to those homozygous for allele 1 (G/G) in SNP-43. Total cholesterol levels increased in T2DM patients who are homozygous for del/ins-19 allele 2, in T2DM patients with the 121/221 haplotype combination, and in control subjects with the haplotype combination 111/121. Conclusion: SNP-44 polymorphism of the calpain-10 gene has a significant association with T2DM patients in the Gaza strip. Certain polymorphisms of calpain-10 also have associations with the levels of total cholesterol in both T2DM patients and controls.
Incidence, Etiology and Risk Factors Associated with Mortality of Nosocomial Candidemia in a Tertiary Care Hospital in Istanbul, Turkey
Authors: Erdem Ilknur , Oguzoglu Naz , Ozturk Engin Derya , Ozgultekin Asu , Sengoz Inan Asuma , Ceran Nurgul , Kaya Fatma , Genc Ipek , Goktas Pasa
Published: September 2010

Objective: The aim of this study was to determine the incidence, etiology and risk factors for mortality of patients with nosocomial candidemia. Subjects and Methods: This observational study was performed at Haydarpasa Numune Training and Research Hospital, a tertiary care hospital with 750 beds, between the years 2004 and 2007. Fifty defined cases with a nosocomial bloodstream infection caused by Candida species were included in the study. All demographic, microbiological and clinical records for each patient were collected using a standardized form. Blood culture was performed by automated blood culture system, and those samples positive for yeast were subcultured on Sabouraud agar. Results: The mean incidence density of nosocomial candidemia was 0.58/10,000 patient-days/year (range 0.17–1.4). Candidemia episodes increased from 0.17/10,000 to 1.4/10,000 patient-days/year (p < 0.0001). Candida albicans and non-albicans Candida accounted for 15 (30%) and 35 (70%) cases, respectively. The overall mortality was 56% and was significantly associated with stayingin the intensive care unit (odds ratio: 3.667, 95% confidence interval: 1.07–12.54, p = 0.034). Conclusion: This study showed that there was a significantly increased trend in the incidence of candidemia with high mortality during the study period.
Development and Validation of a Method for Densitometric Analysis of Berberine in Herbal Extract and Polyherbal Formulation
Authors: Ghosh V.K. , Nagore D.H. , Patil M.J. , Prakash A.
Published: September 2010

Objective: Todevelop a new high-performance thin-layer chromatography (HPTLC) method for the quantification of berberine in herbal extract and pharmaceutical dosage form. Materials and Methods: The HPTLC was performed on aluminium foil plates coated with 200 µm silica gel 60F254. Linear ascending development with toluene:ethyl acetate:formic acid:methanol 9:9:3:1 (v/v/v/v) was performed at room temperature (25 ± 2°C) in a twin-trough glass chamber saturated with mobile-phase vapour. Compact bands (RF 0.58 ± 0.02) were obtained for berberine. Spectrodensitometric scanning was performed in fluorescence mode at 350 nm. The method was validated for precision, recovery, robustness, specificity, and detection and quantification limits, in accordance with International Conference on Harmonization guidelines. Results: Linear regression analysis of the calibration plots showed a good linear relationship (r2 = 0.9996 ± 0.0001) between peak area and concentration in the range 10–100 ng/band, respectively. The limits of detection and quantification were 2.8 and 9.3 ng/band. The recovery of the method was 98.5–100.6%. Conclusion: The above method was a rapid and cost-effective quality-control tool for routine analysis of berberine in herbal extracts and in pharmaceutical dosage form.
Manufacturing Loyalty: The Political Mobilization of Labor in Taiwan, 1950—1986
Authors: Ho Ming-sho
Published: September 2010

Authoritarianism expects workers to play the dual role of diligent producers and loyal citizens simultaneously. In extreme cases, workers must demonstrate political commitment in their everyday life. This article analyzes Taiwanese sugar refinery workers to understand the dynamics of political mobilization under the Nationalists. In the name of anti-communism, a series of control mechanisms were installed in nationalized workplaces. Workers were coerced to participate in numerous political rituals. Beneath superficial conformity, workers adopted a rich variety of everyday techniques of resistance to cope with their dependence. The author characterizes workers’ behaviors in terms of ritualism, innovation, and retreatism. These acts of resistance brought about an undisciplined workplace with widespread work avoidance and moonlighting. Over the long haul, the infrastructure of political mobilization remained intact despite the fact that its content became more and more meaningless. Finally, only with the fundamental change in the political environment brought about by democratization did this labor control strategy finally collapse.
The sustainability of start-up firms among formerly wage-employed workers
Authors: Muñoz-Bullón Fernando , Cueto Begoña
Published: September 2010

In this paper we study the survival of start-up firms among former wage workers in Spain. We use well-known duration model techniques in order to analyse the duration of their self-employment spells distinguishing between those that end in unemployment from those that end in exit to a new paid employment. We address the question of how long these workers remain self-employed before entering into unemployment or returning to paid employment. Our findings show that a higher survival rate in self-employment is associated with men, prime-age workers and individuals with higher previous labour turnover. Moreover, longer unemployment spells are found to speed up the rate of transition to unemployment and to reduce that to paid employment. Finally, the probability of exiting decreases with duration in self-employment, and women are more likely than men to become unemployed after a self-employment experience.
Race, Ethnicity, and Shared Decision Making for Hyperlipidemia and Hypertension Treatment: The DECISIONS Survey
Authors: Ratanawongsa Neda , Zikmund-Fisher Brian J. , Couper Mick P. , Van Hoewyk John , Powe Neil R.
Published: September 2010

Background

Racial/ethnic differences in shared decision making about cardiovascular risk-reduction therapy could affect health disparities.

Objective

To investigate whether patient race/ethnicity is associated with experiences discussing cardiovascular risk-reduction therapy with health care providers.

Setting

National sample of US adults identified by random-digit dialing.

Design

Cross-sectional survey conducted in November 2006 to May 2007.

Participants

Among participants in the National Survey of Medical Decisions (DECISIONS), a nationally representative sample of English-speaking US adults aged 40 and older, the authors analyzed respondents who reported discussing hyperlipidemia or hypertension medications with a health care provider in the previous 2 years.

Measurements

In multivariate linear and logistic regressions adjusting for age, gender, income, insurance status, perceived health, and current therapy, they assessed the relation between race/ethnicity (black/Hispanic v. white) and decision making: knowledge, discussion of pros and cons of therapy, discussion of patient preference, who made the final decision, preferred involvement, and confidence in the decision.

Results

Of respondents who discussed high cholesterol (N = 738) or hypertension (N = 745) medications, 88% were white, 9% black, and 4% Hispanic. Minorities had lower knowledge scores than whites for hyperlipidemia (42% v. 52%, difference –10% [95% confidence interval (CI): 15, –5], P < 0.001), but not for hypertension. For hyperlipidemia, minorities were more likely than whites to report that the health care provider made the final decision for treatment (31.7% v. 12.3% whites, difference 19.4% [95% CI: 6.9, 33.1%], P < 0.01); this was not true for hypertension.

Limitations

Possible limitations include the small percentage of minorities in the sample and potential recall bias.

Conclusions

Minorities considering hyperlipidemia therapy may be less informed about and less involved in the final decision-making process.
Gender, Development, and Neoliberalism: HIV/ AIDS in Cambodia
Authors: Yaşar Yavuz
Published: September 2010

Thanks to the anti-HIV/AIDS measures of international and non-governmental organizations, Cambodia has been considered a successful case in preventing the transmission of the virus. Declaration of such a victory for the Cambodian case is premature, however, given that HIV prevalence continues to rise among women and, according to Cambodian health officials, another wave of epidemic could occur soon. This study discusses how the implementation of neoliberal economic policies without counterbalancing social policy measures undermines the sustainability and effectiveness of such short-term measures by creating a risky environment for the epidemic. Trade liberalization policies have exacerbated poverty, mobility, and gender inequality, making women more susceptible and vulnerable to HIV/AIDS.

JEL classification: I18, F13, O19
Differential Adhesiveness and Neurite-promoting Activity for Neural Cells of Chitosan, Gelatin, and Poly-l-Lysine Films
Authors: Martín-López Eduardo , Nieto-Díaz Manuel , Nieto-Sampedro Manuel
Published: September 2010

Chitosan (Ch) and some of its derivatives have been proposed as good biomaterials for tissue engineering, to construct scaffolds promoting tissue regeneration. In this work we made composite films from Ch and mixtures of Ch with gelatin (G) and poly-l-lysine (PLL), and evaluated the growth on these films of PC12 and C6 lines as well as neurons and glial cells derived from cerebral tissue and dorsal root ganglia (DRG). C6 glioma cells proliferated on Ch, G, and Ch + G films, although metabolic activity was decreased by the presence of the G in the mixtures. NGF-differentiated PC12 cells, adhered preferentially on Ch and films containing PLL. Unlike NGF-treated PC12 cells, cortical and hippocampal neurons showed good adhesion to Ch and Ch + G films, where they extended neurites. Astrocytes adhered on Ch, Ch + G, and Ch + PLL mixtures, although viability decreased during the culture time. Olfactory ensheathing cells (OEC) adhered and proliferated to confluency on the wells covered with Ch + G films. Neurites from DRGs exhibited high extension on these films. These results demonstrate that Ch + G films have excellent adhesive properties for both neurons and regeneration-promoting glia (OEC). These films also promoted neurite extension from DRG, making them good candidates for tissue engineering of nerve repair.
Criminal Legacies: Community Impact Assessments and Defining “Success” and “Harm” in Police Homicide Investigations
Authors: Innes Martin
Published: September 2010

Police investigations of suspected criminal homicides in the United Kingdom are increasingly incorporating attempts to measure the impact of such incidents on communities. Drawing on fieldwork data collected through a programme of research examining social reactions to major crimes, this article explores what such developments might signal about how the criteria for success in police investigative work is being subtly reconfigured.
Questioning Suspects: A Comparative Perspective
Authors: Dixon David
Published: September 2010

This article contrasts the ways in which English-speaking jurisdictions have responded to concerns about practices in the police interrogation of suspects. Since the mid-1990s, a stark contrast has developed between the methods taught to North American police officers via the “Reid Technique” and similar U.S. training programs and the strategy of “investigative interviewing” in England and Wales (and increasingly elsewhere in Europe and Australasia). This policy divergence must be understood in the context of differing responses to miscarriages of justice and investigative failures (caused, at least in part, by inefficient interrogation techniques) and the knowledge which inquiries into these miscarriages and failures produced. While investigative interviewing is part of a response to criminal process failure which sees both wrongful convictions and failed prosecutions as problematic, the United States has been slow to acknowledge the scale of a problem which has not only convicted (and executed) the innocent, but also failed to bring the guilty to justice. Drawing on empirical research in Australia, where audio-visual recording has been used routinely since the early 1990s, the article notes the limits and benefits of electronic recording, which too often is presented as a panacea. The article notes that most discussion of American interrogation takes place in an empirical vacuum and expresses doubts about the prevalent accounts of police practice. It also notes some recent interest in the United States in alternative approaches to interrogating suspects which have developed from the experience of questioning terrorist suspects.
Criminal Profiling and Criminal Investigation
Authors: Devery Christopher
Published: September 2010

A review of the development of criminal profiling demonstrates that profiling has never been a scientific process. It is essentially based on a compendium of common sense intuitions and faulty theoretical assumptions, and in practice appears to consist of little more than educated guesses and wishful thinking. While it is very difficult to find cases where profiling made a critical contribution to an investigation, there exist a number of cases where a profile, combined with investigative and prosecutorial enthusiasm, derailed the investigation and even contributed to serious miscarriages of justice. As a result, police agencies should carefully consider whether the development of in-house profiling capability, or use of external consultants to provide such services, is justified.
Selling Confession: Setting the Stage With the “Sympathetic Detective With a Time-Limited Offer”
Authors: Davis Deborah , Leo Richard A. , Follette William C.
Published: September 2010

The effectiveness of an interrogation tactic dubbed the “sympathetic detective with a time limited offer” was tested. Participants read two versions of an interrogation transcript, with and without the tactic. Those who read the sympathetic detective version believed the detective had greater authority to determine whether and with what to charge the suspect, more beneficent intentions toward the suspect, and viewed confession as more wise. However, regression analyses indicated that for innocent suspects, only perceptions of the strength of evidence against the suspect and the detective’s beneficence and authority predicted the perceived wisdom of false confession. Interrogation tactics were generally effective, as indicated by participant recommendations of confession (vs. invoking Miranda, denial, or continuing to talk without admitting guilt) for both innocent (16.7%) and guilty (74.4%) suspects, and reasons offered for participants’ recommendations for confession versus other choices generally conformed to those reported by real-life confessors and interrogation scholars.
Does Forensic DNA Help to Solve Crime? The Benefit of Sophisticated Answers to Naive Questions
Authors: Wilson David B. , McClure David , Weisburd David
Published: September 2010

Forensic science has played an increasingly important role in the investigation of crimes. We argue in this paper that, in addition to bench science, field experimentation involving forensic methods is critical to properly assess the relative utility of various methods of solving crimes. We illustrate this point by summarizing the findings from a recent Campbell Collaboration systematic review of field studies of the effectiveness of DNA testing. Our search identified five studies, including one randomized-controlled-trial of the value of DNA testing in burglary cases. The findings generally support the value of DNA testing for police investigations, particularly for high volume crimes such as burglary, although most of the empirical evidence is methodologically weak. Additional work is clearly needed, not only with respect to DNA testing but other forensic methods as well.
Functional Impairments in Children With ADHD
Authors: Booster Genery D. , DuPaul George J. , Eiraldi Ricardo , Power Thomas J.
Published: September 2010

Objective: Children with ADHD and comorbid disorders display poorer overall functioning compared with children with ADHD alone, though little research has examined the differential impact of externalizing versus internalizing comorbidities. Method: This study examined the impact of internalizing and externalizing comorbidities on the academic and social functioning of 416 children with ADHD. Results: Children with ADHD and a comorbid externalizing disorder (with or without a concomitant internalizing comorbidity) displayed poorer social skills than those with ADHD alone. Children with ADHD and both an externalizing and internalizing comorbidity exhibited greater homework problems than their ADHD peers with fewer than two types of comorbidity. In addition, older children displayed significantly poorer social skills and greater homework problems than younger children. There was no interaction between comorbid status and age for any measure of academic or social functioning. Conclusion: Results underscore the need for early interventions to address social skills and homework difficulties for children with ADHD and comorbid externalizing disorders.
Mislocalization of Lck impairs thymocyte differentiation and can promote development of thymomas
Authors: Salmond Robert J. , Filby Andrew , Pirinen Niina , Magee Anthony I. , Zamoyska Rose
Published: September 2010

T-cell development is critically dependent on the activities of the Src-family kinases p56lck and p59fyn. While Lck plays a dominant role in the initiation of T-cell receptor (TCR) signaling and in thymocyte differentiation, Fyn plays a more subtle regulatory role. We sought to determine the role of intracellular localization in the differing functions of Lck and Fyn in T cells. By generating transgenic mice that express chimeric Lck-Fyn proteins, we showed that the N-terminal unique domain determines the intracellular localization and function of Lck in pre-TCR and mature αβTCR signaling in vivo. Furthermore, coexpression of a “domain-swap” Lck protein containing the Fyn unique domain with an inducible Lck transgene resulted in the development of thymomas. In contrast to previous reports of Lck-driven thymomas, tumor development was dependent on either pre-TCR or mature TCR signals, and was completely ablated when mice were crossed to a recombination activating gene 1 (Rag1)–deficient background. These data provide a mechanistic basis for the differing roles of Lck and Fyn in T-cell development, and show that intracellular localization as determined by the N-terminal unique domains is critical for Src-family kinase function in vivo.
Complete characterization of the microRNAome in a patient with acute myeloid leukemia
Authors: Ramsingh Giridharan , Koboldt Daniel C. , Trissal Maria , Chiappinelli Katherine B. , Wylie Todd , Koul Sunita , Chang Li-Wei , Nagarajan Rakesh , Fehniger Todd A. , Goodfellow Paul , Magrini Vincent , Wilson Richard K. , Ding Li , Ley Timothy J. , Mardis Elaine R. , Link Daniel C.
Published: September 2010

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and have been implicated in the pathogenesis of cancer. In this study, we applied next generation sequencing techniques to comprehensively assess miRNA expression, identify genetic variants of miRNA genes, and screen for alterations in miRNA binding sites in a patient with acute myeloid leukemia. RNA sequencing of leukemic myeloblasts or CD34+ cells pooled from healthy donors showed that 472 miRNAs were expressed, including 7 novel miRNAs, some of which displayed differential expression. Sequencing of all known miRNA genes revealed several novel germline polymorphisms but no acquired mutations in the leukemia genome. Analysis of the sequence of the 3′-untranslated regions (UTRs) of all coding genes identified a single somatic mutation in the 3′-UTR of TNFAIP2, a known target of the PML-RARα oncogene. This mutation resulted in translational repression of a reporter gene in a Dicer-dependent fashion. This study represents the first complete characterization of the “miRNAome” in a primary human cancer and suggests that generation of miRNA binding sites in the UTR regions of genes is another potential mechanism by which somatic mutations can affect gene expression.
A global optimization algorithm for protein surface alignment
Authors: Bertolazzi Paola , Guerra Concettina , Liuzzi Giampaolo
Published: September 2010

Background

A relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with physico-chemical properties of the site since the conformation, size and chemical composition of the protein surface are all relevant for the interaction with a specific ligand. Several matching strategies have been designed for the recognition of protein-ligand binding sites and of protein-protein interfaces but the problem cannot be considered solved.

Results

In this paper we propose a new method for local structural alignment of protein surfaces based on continuous global optimization techniques. Given the three-dimensional structures of two proteins, the method finds the isometric transformation (rotation plus translation) that best superimposes active regions of two structures. We draw our inspiration from the well-known Iterative Closest Point (ICP) method for three-dimensional (3D) shapes registration. Our main contribution is in the adoption of a controlled random search as a more efficient global optimization approach along with a new dissimilarity measure. The reported computational experience and comparison show viability of the proposed approach.

Conclusions

Our method performs well to detect similarity in binding sites when this in fact exists. In the future we plan to do a more comprehensive evaluation of the method by considering large datasets of non-redundant proteins and applying a clustering technique to the results of all comparisons to classify binding sites.
PpiD is a player in the network of periplasmic chaperones in Escherichia coli
Authors: Matern Yvonne , Barion Birgitta , Behrens-Kneip Susanne
Published: September 2010

Background

The inner membrane-anchored periplasmic folding factor PpiD is described as a parvulin-like peptidyl prolyl isomerase (PPIase) that assists in the maturation of the major beta-barrel outer membrane proteins (OMPs) of Escherichia coli. More recent work however, calls these findings into question. Here, we re-examined the role of PpiD in the E. coli periplasm by analyzing its functional interplay with other folding factors that influence OMP maturation as well as general protein folding in the periplasmic compartment of the cell, such as SurA, Skp, and DegP.

Results

The analysis of the effects of both deletion and overexpression of ppiD on cell envelope phenotypes revealed that PpiD in contrast to prior observations plays only a minor role, if any, in the maturation of OMPs and cannot compensate for the lack of SurA in the periplasm. On the other hand, our results show that overproduction of PpiD rescues a surA skp double mutant from lethality. In the presence of increased PpiD levels surA skp cells show reduced activities of both the SigmaE-dependent and the Cpx envelope stress responses, and contain increased amounts of folded species of the major OMP OmpA. These effects require the anchoring of PpiD in the inner membrane but are independent of its parvulin-like PPIase domain. Moreover, a PpiD protein lacking the PPIase domain also complements the growth defects of an fkpA ppiD surA triple PPIase mutant and exhibits chaperone activity in vitro. In addition, PpiD appears to collaborate with DegP, as deletion of ppiD confers a temperature-dependent conditional synthetic phenotype in a degP mutant.

Conclusions

This study provides first direct evidence that PpiD functions as a chaperone and contributes to the network of periplasmic chaperone activities without being specifically involved in OMP maturation. Consistent with previous work, our data support a model in which the chaperone function of PpiD is used to aid in the early periplasmic folding of many newly translocated proteins.