bluuebunny/crossref_metadata_2025 huggingface dataset:
The α2adrenoceptor antagonist idazoxan alleviatesl‐DOPA‐induced dyskinesia by reduction of striatal dopamine levels: anin vivomicrodialysis study in 6‐hydroxydopamine‐lesioned rats
Authors: Buck Kerstin , Voehringer Patrizia , Ferger Boris
Published: November 2009

l‐DOPA‐induced dyskinesia is characterised by debilitating involuntary movement, which limits quality of life in patients suffering from Parkinson’s disease. Here, we investigate effects of the α2adrenoceptor antagonist idazoxan onl‐DOPA‐induced dyskinesia as well as on alterations of extracellularl‐DOPA and dopamine (DA) levels in the striatum in dyskinetic rats. Male Wistar rats were unilaterally lesioned with 6‐hydroxydopamine and subsequently treated withl‐DOPA/benserazide to induce stable dyskinetic movements. Administration of idazoxan [(9 mg/kg, intraperitoneal (i.p.)] significantly alleviatedl‐DOPA‐induced dyskinesia, whereas idazoxan (3 mg/kg, i.p.) did not affect dyskinetic behaviour. Bilateralin vivomicrodialysis revealed that idazoxan 9 mg/kg reduces extracellular peakl‐DOPA levels in the lesioned and intact striatum as well as DA levels in the lesioned striatum. In parallel, the exposure to idazoxan in the striatum was monitored. Furthermore, no idazoxan andl‐DOPA drug–drug interaction was found in plasma, brain tissue and CSF. In conclusion, the decrease ofl‐DOPA‐derived extracellular DA levels in the lesioned striatum significantly contributes to the anti‐dyskinetic effect of idazoxan.
Nitric oxide sensitive guanylyl cyclase activity decreases during cerebral postnatal development because of a reduction in heterodimerization
Authors: Haase Nadine , Haase Tobias , Seeanner Monika , Behrends Soenke
Published: November 2009

Soluble guanylyl cyclase (sGC) is the major physiological receptor for nitric oxide (NO) throughout the central nervous system. Three different subunits form the α1/β1 and α2/β1 heterodimeric enzymes that catalyze the reaction of GTP to the second messenger cGMP. Both forms contain a prosthetic heme group which binds NO and mediates activation by NO. A number of studies have shown that NO/cGMP signaling plays a major role in neuronal cell differentiation during development of the central nervous system. In the present work, we studied regulation and expression of sGC in brain of rats during postnatal development using biochemical methods. We consistently observed a surprising decrease in cerebral NO sensitive enzyme activity in adult animals in spite of stable expression of sGC subunits. Total hemoprotein heme content was decreased in cerebrum of adult animals, likely because of an increase in heme oxygenase activity. But the loss of sGC activity was not simply because of heme loss in intact heterodimeric enzymes. This was shown by enzyme activity determinations with cinaciguat which can be used to test heme occupancy in intact heterodimers. A reduction in heterodimerization in cerebrum of adult animals was demonstrated by co‐precipitation analysis of sGC subunits. This explained the observed decrease in NO sensitive guanylyl cyclase activity in cerebrum of adult animals. We conclude that differing efficiencies in heterodimer formation may be an important reason for the lack of correlation between sGC protein expression and sGC activity that has been described previously. We suggest that heterodimerization of sGC is a regulated process that changes during cerebral postnatal development because of still unknown signaling mechanisms.
Inhibiting p53 pathways in microglia attenuates microglial‐evoked neurotoxicity following exposure to Alzheimer peptides
Authors: Davenport Christopher M. , Sevastou Ioanna G. , Hooper Claudie , Pocock Jennifer M.
Published: November 2009

Microglial activation can lead to microglial apoptosis, which may serve to remove highly reactive and possibly neurotoxic microglia. However the loss of microglia may have consequences for future recovery, protection and repair. P53, a nuclear phosphoprotein transcription factor, is critical for activating the expression of genes involved in cell‐cycle arrest and stress‐induced apoptosis. In neurodegenerative diseases the expression of p53 is significantly increased in glial cells, and microglial numbers fall. Following activation with chromogranin A (100 nM), or β‐amyloid25‐35, (10 μM), microglia became apoptotic. Furthermore, p53 expression was enhanced, peaking at 4–6 h after exposure to activators. The p53 transcription inhibitor, pifithrin‐α, (10 μM) significantly reduced the expression of p53 in microglia and significantly modulated the levels of microglial apoptosis induced by activation. Lithium chloride (5 mM), which can modulate p53‐mediated pathways, also reduced p53 expression and reduced microglial apoptosis suggesting glycogen synthase kinase‐3 plays a role. Regulating p53 pathways modulated microglial inducible nitric oxide synthase expression and tumour necrosis factor alpha secretion. Inhibiting p53 mediated microglial apoptosis prevented microglial neurotoxicity suggesting targeting of p53‐mediated pathways in microglia may have therapeutic benefit in Alzheimer’s disease.
Influence of an invasive ant on grazing and detrital communities and nutrient fluxes in a tropical forest
Authors: Dunham Amy E. , Mikheyev Alexander S.
Published: November 2009

Aim Pathways linking grazing and detrital subsystems of terrestrial ecosystems are important for ecosystem processes and function, but remain poorly understood. The invasion of a generalist predator creates a unique opportunity to study the effects of predation across these subsystems. We examine here, the effects of a non‐native generalist predator, the little red fire ant (Wasmannia auropunctata,Roger) on both grazing and detrital invertebrate communities and ecosystem processes in a rain forest understorey.

Location Gamba Protected Area Complex, south‐western Gabon, Africa.

Methods We measured abundances and diversities of understorey grazing and detrital invertebrate communities, soil nutrients, herbivory, litter fragmentation rates and leaf chemistry of a dominant understorey shrub inside and outside of 19 separate invasion fronts. We then explored possible trophic cascades and pathways of interaction using path analysis.

Results Results suggest that invasive ants may alter herbivory regimes, grazing and detrital communities, and may indirectly alter litter decomposition and nutrient cycling in the soil by suppressing important microbivore and detritivore populations with consequences for leaf chemistry.

Main conclusions These results demonstrate that generalist predators may be major drivers of both grazing and detrital subsystems by inducing strong shifts in adjacent communities that ultimately affect ecosystem processes.
Fatal liver injury associated with clopidogrel
Authors: Kastalli Sarrah , El Aïdli Sihem , Zaïem Ahmed , Ben Abdallah Hatem , Daghfous Riadh
Published: November 2009

Clopidogrel, an adenosine diphosphate receptor blocker, is widely used as an adjunctive antiplatelet therapy in acute coronary syndrome and percutaneous coronary stenting. It appears to be a safe drug with few occurrences of liver side‐effects that usually resolved after drug withdrawal. We report a serious liver injury with fatal outcome in a 63‐year‐old man developed 19 days after starting clopidogrel for percutaneous coronary stenting.
TESTING FOR PRO‐POORNESS OF GROWTH, WITH AN APPLICATION TO MEXICO
Authors: Araar Abdelkrim , Duclos Jean‐Yves , Audet Mathieu , Makdissi Paul
Published: November 2009

This paper proposes techniques to test for whether growth has been pro‐poor. We first review different definitions of pro‐poorness and argue for the use of methods that can generate results that are robust over classes of pro‐poor measures and ranges of poverty lines. We then provide statistical procedures that rely on the use of sample data to infer whether growth has been pro‐poor in a population. We apply these procedures to Mexican household surveys for 1992, 1998, and 2004. We find strong normative and statistical evidence that Mexican growth has been absolutely anti‐poor between 1992 and 1998, absolutely pro‐poor between 1998 and 2004 and between 1992 and 2004, and relatively pro‐poor between 1992 and 2004 and between 1998 and 2004. The relative assessment of the period between 1992 and 1998 is statistically too weak to lead to a robust evaluation of that period.
Incidence of seizures associated with iopamidol or iomeprol myelography in dogs with intervertebral disk disease: 161 cases (2000–2002)
Authors: Lexmaulova Leona , Zatloukal Josef , Proks Pavel , Dvorak Milan , Srnec Robert , Rauser Petr , Kecova Helga , Necas Alois
Published: November 2009

Objective –To compare the incidence of seizures in dogs with intervertebral disk disease after iopamidol or iomeprol myelography, and to assess whether the incidence of seizures differed between the 2 agents when severity of neurological deficits, location of cord compression, duration of anesthesia, site of myelogram, volume of contrast, and concentration of contrast were evaluated.

Design –Retrospective study.

Setting –Veterinary teaching hospital.

Animals –One hundred and sixty‐one client‐owned dogs with intervertebral disk disease.

Interventions –Subarachnoid injection of contrast medium.

Measurements and Main Results –One hundred and sixty‐one dogs with intervertebral disk disease were subjected to myelography using iopamidol (n=74) or iomeprol (n=87). Cranial myelography was performed in 31 dogs, caudal myelography in 125 and both cranial and caudal myelography in 5. Seizures occurred in 23 of 161 (14%) dogs. There was no significant difference overall between iopamidol and iomeprol myelography. However, in dogs with thoracolumbar disk extrusion and paraplegia, seizures occurred more frequently after caudal myelography using iopamidol compared with iomeprol.

Conclusions –Both iomeprol and iopamidol are suitable for myelography in dogs. Iomeprol is recommended for caudal myelography in paraplegic dogs with thoracolumbar disk extrusion due to the higher incidence of seizures in this group when iopamidol was used.
Effect of body position on the arterial partial pressures of oxygen and carbon dioxide in spontaneously breathing, conscious dogs in an intensive care unit
Authors: McMillan Matthew W. , Whitaker Katie E. , Hughes Dez , Brodbelt David C. , Boag Amanda K.
Published: November 2009

Objective –To evaluate the effect of body position on the arterial partial pressures of oxygen and carbon dioxide (PaO2, PaCO2), and the efficiency of pulmonary oxygen uptake as estimated by alveolar‐arterial oxygen difference (A‐a difference).

Design –Prospective, randomized, crossover study.

Setting –University teaching hospital, intensive care unit.

Animals –Twenty‐one spontaneously breathing, conscious, canine patients with arterial catheters placed as part of their management strategy.

Interventions –Patients were placed randomly into lateral or sternal recumbency. PaO2and PaCO2were measured after 15 minutes in this position. Patients were then repositioned into the opposite position and after 15 minutes the parameters were remeasured.

Measurements and Main Results –Results presented as median (interquartile range). PaO2was significantly higher (P=0.001) when patients were positioned in sternal, 91.2 mm Hg (86.0–96.1 mm Hg), compared with lateral recumbency, 86.4 mm Hg (73.9–90.9 mm Hg). The median change was 5.4 mm Hg (1.1–17.9 mm Hg). All 7 dogs with a PaO2<80 mm Hg in lateral recumbency had improved arterial oxygenation in sternal recumbency, median increase 17.4 mm Hg with a range of 3.8–29.7 mm Hg. PaCO2levels when patients were in sternal recumbency, 30.5 mm Hg (27.3–32.7 mm Hg) were not significantly different from those in lateral recumbency, 32.2 mm Hg (28.3–36.0 mm Hg) (P=0.07). The median change was −1.9 mm Hg (−3.6–0.77 mm Hg). A‐a differences were significantly lower (P=0.005) when patients were positioned in sternal recumbency, 21.7 mm Hg (17.3–27.7 mm Hg), compared with lateral recumbency, 24.6 mm Hg (20.4–36.3 mm Hg). The median change was −3.1 mm Hg (−14.6–0.9 mm Hg).

Conclusions –PaO2was significantly higher when animals were positioned in sternal recumbency compared with lateral recumbency, predominantly due to improved pulmonary oxygen uptake (decreased A‐a difference) rather than increased alveolar ventilation (decreased PaCO2). Patients with hypoxemia (defined as PaO2<80 mm Hg) in lateral recumbency may benefit from being placed in sternal recumbency. Sternal recumbency is recommended to improve oxygenation in hypoxemic patients.
On the Riskiness of Universal Banking: Evidence from Banks in the Investment Banking Business Pre‐ and Post‐GLBA
Authors: GEYFMAN VICTORIA , YEAGER TIMOTHY J.
Published: November 2009

We explore whether an economically significant differential exists in market‐based risk measures between universal banks and traditional banks. Using a three‐asset portfolio regression model, we find that between 1990 and 2007—a period of gradual deregulation culminating in passage of the Gramm–Leach–Bliley Act (GLBA) of 1999—an increased participation in investment banking was associated with higher total and unsystematic risks and no significant change in systematic risk. Small risk‐reduction benefits emerged in the post‐GLBA era, but such benefits were likely the result of the particular sample period rather than a fundamental change in bank structure following the GLBA. Our results cannot justify the GLBA on risk‐reduction grounds, though the Act may be defensible for other reasons.
The Taylor Principle and Monetary Policy Approaching a Zero Bound on Nominal Rates: Quantile Regression Results for the United States and Japan
Authors: CHEVAPATRAKUL THANASET , KIM TAE‐HWAN , MIZEN PAUL
Published: November 2009

This paper offers a new approach that estimates the response of interest rates to inflation and the output gap at various points (quantiles) on the conditional distribution of interest rates. This offers an improvement on empirical estimates conducted only at the mean and also allows us to test the propositions that policy shows greater aggression to inflation in the reaction function in terms of a greater response coefficient as interest rates reach low levels, and increasing aggression as the lower bound is approached. We find support for the Taylor principle, a more aggressive response to inflation than under a Taylor rule, but no detectable evidence of increasing aggression as the zero lower bound is approached in the US and Japan.
Using Survey Data to Correct the Bias in Policy Expectations Extracted from Fed Funds Futures
Authors: ICHIUE HIBIKI , YUYAMA TOMONORI
Published: November 2009

Many studies estimate risk premiums on federal funds futures to extract monetary policy expectations by assuming that average forecast errors of the expectations are zero or that survey forecasts are good proxies for the expectations. These assumptions, however, may fail due to an unanticipated declining trend in the federal funds rate and to survey respondents' strategic behavior. Consequently, the premiums estimated under these assumptions may be biased. We propose a new method to estimate the premiums and find that the premiums have been often negative since 2000, which is generally consistent with the negative betas observed in the 2000s.
Fundamental Economic Shocks and the Macroeconomy
Authors: EVANS CHARLES L. , MARSHALL DAVID A.
Published: November 2009

We ask how macroeconomic and financial variables respond to empirical measures of shocks to technology, labor supply, and monetary policy. These three shocks account for the preponderance of output, productivity, and price fluctuations. Only technology shocks have a permanent impact on economic activity. Labor inputs have little initial response to technology shocks. Monetary policy has a small response to technology shocks but “leans against the wind” in response to the more cyclical labor supply shock. This shock has the biggest impact on interest rates. Stock prices respond to all three shocks. Other empirical implications of our approach are discussed.
In Defense of Usury Laws
Authors: COCO GIUSEPPE , DE MEZA DAVID
Published: November 2009

Usury law is often criticized by economists for curtailing lending and thus creating deadweight costs. This paper shows that if moral hazard leads to credit rationing, a just‐binding usury law creates a deadweight gain. This property also holds in most market‐clearing equilibria. Independent of social insurance benefits, or curbing present‐biased preferences, interest rate caps have merit.
Insurance Company Employees' Financial Expertise and Practices: Implications on Benefit Participation and Satisfaction
Authors: Power Mark L. , Hira Tahira K.
Published: November 2009

Abstract

Employers continue to shift financial decision‐making responsibility for employee benefits to employees. This article examines employees' financial practices, financial expertise, and levels of benefit participation and overall satisfaction. We show that there are significant differences in employees' financial practices and financial expertise based on socio‐demographic characteristics. While levels of benefit satisfaction and employer ranking are high, significant differences in how employees feel toward their employer exist. Employees more highly value traditional benefits than nontraditional benefits, but satisfaction with benefits was high regardless of take‐up rate. We also find that respondents are more knowledgeable over experiential financial concepts than more specific financial concepts like qualifying conditions for a traditional individual retirement account. Employer‐sponsored financial education programs, which increase employee understanding of employer‐provided benefits and their importance to employees' financial well‐being, should improve overall employee satisfaction, loyalty, and productivity.
Perspectives Articles:Exploring Stakeholder Perspectives on What Is Affordable Health Care
Authors: Rosenberg Marjorie A. , Johnson, Jr. Paul H. , Duncan Ian G.
Published: November 2009

Abstract

Health care expenditures have accounted for increasing proportions of the U.S. gross domestic product, and the rate of growth of health care expenditures has increased over the past two decades. These two measures of assessing whether the level of health care expenditures is affordable may be appropriate in the aggregate for the United States but are not appropriate to assess whether individual stakeholder groups can afford their particular level of spending on health care. Health care is an economic good that differs from other economic goods, as it involves life and death issues, and invokes a call for a moral authority. This article explores definitions of what is affordable health care from the perspective of different stakeholders and suggests that other measures are needed to assess whether or not health care is affordable for stakeholders as one definition is not appropriate for all stakeholders.
Community unionism versus business unionism: The return of the moral economy in trade union studies
Authors: MOLLONA MASSIMILIANO
Published: November 2009

In this article, I discuss different forms of working‐class activism in two steel factories in Sheffield, England, where I conducted fieldwork between 1999 and 2000. Locating the ethnography in the broader context of the U.K.'s financial capitalism, I describe how the models of “community unionism” and “business unionism” were implemented on the two shop floors, affecting the work practices, political strategies, and forms of solidarities of workers. I show, first, how the current financialization of the economy challenges existing labor strategies, leading to new political solidarities and moralities of labor. Second, I use current debates on trade union activism to think anthropologically about class, labor, and the relations between society and the economy under capitalism.
The optimal sacrifice: A study of voluntary death among the Siberian Chukchi
Authors: WILLERSLEV RANE
Published: November 2009

In the Siberian North, “voluntary death,” that is, a person, who—often because of illness and old age—requests to die at the hands of close relatives, has traditionally been explained as a form of suicide resulting from the region's harsh living conditions. In this article, I suggest an alternative interpretation. Drawing on ethnographic data collected among the Chukchi of northern Kamchatka, I argue that voluntary death is effectively a ritual blood sacrifice. In making this argument, I recast long‐standing debates about sacrifice by suggesting that behind the triangular relationship of sacrificer, deity, and victim lies a structure of ideal sacrifice, which is the impossible act of self‐sacrifice. This structure, in turn, makes it possible to conceive of voluntary death as categorically different from suicide—indeed, as a ritual inversion of suicide.
Rhinestone aesthetics and religious essence: Looking Jewish in Paris
Authors: ARKIN KIMBERLY A.
Published: November 2009

I explore the paradoxical construction of race through fashion among the Parisian children and grandchildren of upwardly mobile immigrant North African Jews. Faced with the conflation of North Africanity and inassimilable difference, Sephardi youth escaped some forms of French racism by enacting others. By essentializing and individualizing Jewishness through conspicuous consumption, they made Frenchness possible for “Arab Jews” in ways foreclosed to Arab Muslims. But these same practices also helped fashion and biologize their exclusion from the French nation. Rather than encourage the deconstruction of “modern” identity narratives, Sephardi youth liminality thus encouraged the reessentialization of class, ethnicity, religion, and nation.
The orthodoxization of ritual practice in western Anatolia
Authors: HART KIMBERLY
Published: November 2009

In rural western Turkey, villagers have replaced male performances of davul (bass drum) and zurna (double‐reed wind instrument) as well as men's dancing with mevluts, special prayer services, and they have replaced women's dances to taped or live electric harmonium music with sohbets, sermons. Villagers are motivated to transform “cultural practices” that appear “backward” from the perspective of state‐based ideologies of cultural progress and that are considered sinful from the perspective of Islamists. I trace their quests for spiritual and secular salvation and how they relate to the construction of a modernist Islamic worldview.
Remembering across the border: Postsocialist nostalgia among Turkish immigrants from Bulgaria
Authors: PARLA AYSE
Published: November 2009

“Postsocialist nostalgia” among Turkish immigrant women from Bulgaria is not just strategic performance to negotiate the challenges that face working women in Turkey but is also cross‐cultural analysis based on the migrants’ experiences of distinct gender regimes on the two sides of the border. I explore why the competition between established residents and newcomers over scarce resources becomes, in this instance, the ground for negotiation over proper gender roles. I also suggest that the migrants’ appeal to the communist legacy posits an alternative to either “normalizing” or “Orwellizing” communism and that it offers a more nuanced understanding of the norms and practices of gender and labor under communism, as experienced by this particular group of minority women.
Electroconvulsive therapy is equally effective in unipolar and bipolar depression
Authors: Bailine S. , Fink M. , Knapp R. , Petrides G. , Husain M. M. , Rasmussen K. , Sampson S. , Mueller M. , McClintock S. M. , Tobias K. G. , Kellner C. H.
Published: November 2009

Bailine S, Fink M, Knapp R, Petrides G, Husain MM, Rasmussen K, Sampson S, Mueller M, McClintock SM, Tobias KG, Kellner CH. Electroconvulsive therapy is equally effective in unipolar and bipolar depression.

Objective:  To determine the relative efficacy of electroconvulsive therapy (ECT) in the treatment of bipolar (BP) and unipolar (UP) depressive illness and clarify its role in BP depression.

Method:  Patients referred for ECT with both UP and BP depressions. [classified by Structured Clinical Interview for DSM (SCID‐I) criteria for history of mania] were included in a multi‐site collaborative, double‐masked, randomized controlled trial of three electrode placements – right unilateral, bifrontal or bitemporal – in a permutated block randomization scheme.

Results:  Of 220 patients, 170 patients (77.3%) were classified as UP and 50 (22.7%) as BP depression in the intent‐to‐treat sample. The remission and response rates and numbers of ECT for both groups were equivalent.

Conclusion:  Both UP and BP depressions remit with ECT. Polarity is not a factor in the response rate. In this sample ECT did not precipitate mania in depressed patients. Treatment algorithms for UP and BP depression warrant re‐evaluation.
Impact of substance use on the physical health of patients with bipolar disorder
Authors: Garcia‐Portilla M. P. , Saiz P. A. , Benabarre A. , Florez G. , Bascaran M. T. , Díaz E. M. , Bousoño M. , Bobes J.
Published: November 2009

Garcia‐Portilla MP, Saiz PA, Benabarre A, Florez G, Bascaran MT, Díaz EM, Bousoño M, Bobes J. Impact of substance use on the physical health of patients with bipolar disorder.

Objective:  To describe the impact of tobacco, alcohol and cannabis on metabolic profile and cardiovascular risk in bipolar patients.

Method:  Naturalistic, cross‐sectional, multicenter Spanish study. Current use of tobacco, alcohol and cannabis was determined based on patient self‐reports. Metabolic syndrome was defined using the National Health and Nutrition Examination Survey 1999–2000 and the American Heart Association/National Heart, Lung and Blood Institute criteria, and cardiovascular risk using the Framingham and the Systematic Coronary Risk Evaluation functions.

Results:  Mean age was 46.6 years, 49% were male. Substance use: 51% tobacco, 13% alcohol and 12.5% cannabis. Patients who reported consuming any substance were significantly younger and a higher proportion was male. After controlling for confounding factors, tobacco was a risk factor for coronary heart disease (CHD) (unstandardized linear regression coefficient 3.47, 95% confidence interval 1.85–5.10).

Conclusion:  Substance use, mainly tobacco, was common in bipolar patients. Tobacco use negatively impacted CHD risk.
Personality disorders improve in patients treated for major depression
Authors: Mulder R. T. , Joyce P. R. , Frampton C. M. A.
Published: November 2009

Mulder RT, Joyce PR, Frampton CMA. Personality disorders improve in patients treated for major depression.

Objective:  To examine the stability of personality disorders and their change in response to the treatment of major depression.

Method:  149 depressed out‐patients taking part in a treatment study were systematically assessed for personality disorders at baseline and after 18 months of treatment using the SCID‐II.

Results:  Personality disorder diagnoses and symptoms demonstrated low‐to‐moderate stability (overall κ = 0.41). In general, personality disorder diagnoses and symptoms significantly reduced over the 18 months of treatment. There was a trend for the patients who had a better response to treatment to lose more personality disorder symptoms, but even those who never recovered from their depression over the 18 months of treatment lost, on average, nearly three personality disorder symptoms.

Conclusion:  Personality disorders are neither particularly stable nor treatment resistant. In depressed out‐patients, personality disorder symptoms in general improve significantly even in patients whose response to their treatment for depressive symptoms is modest or poor.
Applicability of IG/TCR gene rearrangements as targets for minimal residual disease assessment in a population‐based cohort of Swedish childhood acute lymphoblastic leukaemia diagnosed 2002–2006
Authors: Thörn Ingrid , Forestier Erik , Thuresson Britt , Wasslavik Carina , Malec Maria , Li Aihong , Lindström‐Eriksson Elenor , Botling Johan , Barbany Gisela , Jacobsson Stefan , Olofsson Tor , Porwit Anna , Sundström Christer , Rosenquist Richard
Published: November 2009

Minimal residual disease (MRD) detection during the early treatment phase has become an important stratification parameter in many childhood acute lymphoblastic leukaemia (ALL) treatment protocols. Here, we aimed to address the applicability of rearranged antigen‐receptor genes as potential MRD markers using real‐time quantitative polymerase chain reaction (RQ‐PCR) in a Swedish population‐based cohort. From 334 childhood ALL cases diagnosed during 2002–2006, we analysed 279 diagnostic samples (84%) by screening for rearranged immunoglobulin (IG) and T‐cell receptor (TCR) genes. Allele‐specific oligonucleotides were designed, and the sensitivity and quantitative level was determined for each target. Overall, clonal IG/TCR rearrangements were detected in 97% (236/244) of B‐cell precursor ALL (BCP ALL) and 94% (33/35) of T‐ALL. A sensitive RQ‐PCR analysis (≤10−4) was obtained in 89% (216/244) of BCP ALL and in 74% (26/35) of T‐ALL, whereas two sensitive targets were only available in 47% (115/244) of BCP ALL and 29% (10/35) of T‐ALL cases. With the stratification threshold of ≥10−3, which is applied in the current Nordic treatment protocol (NOPHO‐ALL 2008) for the identification of high‐risk patients, 93% of BCP ALL and 86% of T‐ALL reached this quantitative range by at least one target gene. Taken together, this national retrospective study demonstrates that an IG/TCR target for MRD monitoring can be identified in the majority of childhood ALL cases, whereas identification of a second sensitive target gene needs to be improved.
ORIGINAL ARTICLE: Thrombin Activatable Fibrinolysis Inhibitor and Clot Lysis Time in Pregnant Patients with Antiphospholipid Syndrome: Relationship with Pregnancy Outcome and Thrombosis
Authors: Martinez‐Zamora Maria Angeles , Tassies Dolors , Carmona Francisco , Espinosa Gerard , Cervera Ricard , Reverter Juan Carlos , Balasch Juan
Published: November 2009

Problem  Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis.

Method of study  Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined.

Results  Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences.

Conclusion  Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS.
ORIGINAL ARTICLE: Effect of Maternal Immunopotentiation on Apoptosis‐Associated Molecules Expression in Teratogen‐Treated Embryos
Authors: Savion Shoshana , Aroch Ilan , Mammon Keren , Orenstein Hasida , Fein Amos , Torchinsky Arkady , Toder Vladimir
Published: November 2009

Problem  Potentiation of the maternal immune system was shown by us to affect the embryonic response to teratogenic insults. In order to understand better the mechanisms underlying that phenomenon, we explored the effect of maternal immunopotentiation by rat splenocytes on the early stages of the embryonic response to cyclophosphamide (CP).

Method of study  Immunopotentiated CP‐treated embryos were analysed for cell cycle changes by flow cytometry, while cell proliferation and apoptosis were assessed by 5′‐bromo‐2′‐deoxyuridine (BrdU) incorporation and terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP‐biotin nick‐end labeling (TUNEL) respectively. The expression of the p65 subunit of NF‐κB, IκBα, Bax, bcl‐2 and p53 was assessed by flow cytometry.

Results  Exposure to CP resulted in significant growth retardation and in the appearance of cellular damage, a reduction in cell proliferation and the appearance of apoptotic cells, which were all found to be delayed in immunopotentiated embryos. In parallel, CP‐treated embryos demonstrated a reduction in the percentage of p65‐ or IκBα‐positive cells, while the percentage of bcl‐2‐ or p53‐positive cells increased initially and decreased later. Those changes were normalized by maternal immunopotentiation when tested at 24 hrs after exposure to the teratogen.

Conclusion  Our data implicate maternal immunopotentiation to protect the embryo against teratogenic insults, possibly through its effect on the expression of p65, bcl‐2 or p53.
ORIGINAL ARTICLE: Phenotypic Characterization of Macrophages in the Endometrium of the Pregnant Cow
Authors: Oliveira Lilian J. , Hansen Peter J.
Published: November 2009

Problem Macrophages are recruited in large number to the interplacentomal endometrium of the cow during pregnancy. We evaluated whether endometrial macrophages also accumulate in placentomal regions of endometrium during pregnancy and whether endometrial macrophages are regionally differentiated.

Method of study Interplacentomal endometrium and placentomes were subjected to dual‐color immunofluorescence using CD68 as a pan‐macrophage marker.

Results CD68+cells were abundant in stroma of the interplacentomal endometrium and caruncular septa of the placentomes. CD68+cells were not present in fetal villi of the placentomes or in the interplacentomal chorion. Regardless of location, the majority of CD68+cells also expressed CD14. In interplacentomal endometrium, CD68+CD11b+cells were present in deeper areas of the stroma but not in shallow endometrial stroma. In caruncular septa of the placentome, CD68+cells were negative for CD11b. CD68+cells in the interplacentomal endometrium were negative for MHC class II while most CD68+cells in caruncular septa were positive for MHC class II.

Conclusion CD68+CD14+macrophages present in the stroma of the interplacentomal endometrium and caruncular septa of the placentome are regionally differentiated with regard to expression of CD11b and MHC class II.
Psychosocial interventions for bipolar disorder
Authors: Castle David J. , Berk Lesley , Lauder Sue , Berk Michael , Murray Greg
Published: November 2009

Aim:

To provide a selected overview of the literature on psychosocial treatments for bipolar disorder

Method:

Selective literature review

Results:

Randomised controlled trials of psychosocial interventions in bipolar disorder fall largely into five categories, namely: psychoeducation, integrated treatments, family based therapy, cognitive behavioural therapy and interpersonal social rhythm therapy. Most studies have shown some benefit in terms of relapse prevention, but have tended to be effective for either the depressed or the manic pole, and not both. Broader outcome parameters such as quality of life have not been reported consistently. The mechanisms whereby treatments might exert their effects have not been clearly delineated. Many studies have excluded patients with bipolar II and other variants, and those with psychiatric and substance use comorbidities, reducing their generalisability.

Discussion:

Whilst psychosocial treatments show promise in the area of bipolar disorder, more work is required to delineate the effective elements of such interventions, and to ensure generalisability to individuals with bipolar II and other forms of bipolar disorder, as well as those with psychiatric and substance use comorbidities. Other forms of delivery, such as via the internet, deserve further exploration.
Phosphopantetheinyl transferase inhibition and secondary metabolism
Authors: Foley Timothy L. , Young Brian S. , Burkart Michael D.
Published: November 2009

Efforts to isolate carrier protein‐mediated synthases from natural product‐producing organisms using reporter‐linked post‐translational modification have been complicated by the efficiency of the endogenous process. To address this issue, we chose to target endogenous phosphopantetheinyl transferases (PPTases) for inhibitor design to facilitate natural product synthase isolation through a chemical genetics approach. Herein we validate secondary metabolism‐associated PPTase for chemical probe development. We synthesized and evaluated a panel of compounds based on the anthranilate 4H‐oxazol‐5‐one pharmacophore previously described to attenuate PPTase activity within bacterial cultures. Through the use of a new high‐throughput Förster resonance energy transfer assay, we demonstrated that these compounds exclusively inhibit fatty acid synthase‐specific PPTases. In vivo, a lead compound within this panel demonstrated selective antibiotic activity in a Bacillus subtilis model. Further evaluation demonstrated that the compound enhances actinorhodin production in Streptomyces coelicolor, revealing the ability of this class of molecules to stimulate precocious secondary metabolite production.
Alanine aminotransferase of Trypanosoma brucei– a key role in proline metabolism in procyclic life forms
Authors: Spitznagel Diana , Ebikeme Charles , Biran Marc , Nic a′ Bháird Nóirín , Bringaud Frédéric , Henehan Gary T. M. , Nolan Derek P.
Published: November 2009

African trypanosomes possess high levels of alanine aminotransferase (EC 2.6.1.2), although the function of their activity remains enigmatic, especially in slender bloodstream forms where the metabolism of ketoacids does not occur. Therefore, the gene for alanine aminotransferase enzyme in Trypanosoma brucei (TbAAT) was characterized and its function assessed using a combination of RNA interference and gene knockout approaches. Surprisingly, as much as 95% or more of the activity appears to be unnecessary for growth of either bloodstream or procyclic forms respiring on glucose. A combination of RNA interference and NMR spectroscopy revealed an important role for the activity in procyclic forms respiring on proline. Under these conditions, the major end product of proline metabolism is alanine, and a reduction in TbAAT activity led to a proportionate decrease in the amount of alanine excreted along with an increase in the doubling time of the cells. These results provide evidence of a role for alanine aminotransferase in the metabolism of proline in African trypanosomes by linking glutamate produced by the initial oxidative steps of the pathway with pyruvate produced by the final oxidative step of the pathway. This step appears to be essential when proline is the primary carbon source, which is likely to be the physiological situation in the tsetse fly vector.
Educational Policy and Country Outcomes in International Cognitive Competence Studies
Authors: Rindermann Heiner , Ceci Stephen J.
Published: November 2009

Prior studies of studentsqqaposxx and adultsqqaposxx cognitive competence have shown large differences between nations, equivalent to a difference of 5 to 10 years of schooling. These differences seem to be relevant because studies using different research paradigms have demonstrated that population-level cognitive abilities are related to a number of important societal outcomes, including productivity, democratization, and health. In this overview of transnational differences, we document a number of positive predictors of international differences in student competence, including the amount of preschool education, student discipline, quantity of education, attendance at additional schools, early tracking, the use of centralized exams and high-stakes tests, and adult educational attainment. We found rather negative relationships for grade retention rates, age of school onset, and class size. Altogether, these results, when combined with the outcomes of earlier studies, demonstrate that international differences in cognitive competence can be explained in part by aspects of the respective countriesqqaposxx educational systems and that these differences consequently can be reduced by reform of their educational policy. This has important implications not just for closing gaps in educational achievement, but for narrowing international gaps in wealth, health, and democracy.
Monitoring Matters
Authors: Lac Andrew , Crano William D.
Published: November 2009

Parental monitoring is commonly accredited as an important protective factor against risky adolescent behaviors. In this meta-analytic review, associations of adolescents' perceptions of parental monitoring with adolescent marijuana use were collected and quantified across 25 independent samples from 17 empirical studies involving 35,367 unique participants. Applying a random-effects model, the average magnitude of effect was r = –.21. The association was significantly stronger in female-only samples (r = –.31 vs. r = –.19, p < .001) and when parental monitoring was defined purely in terms of parental knowledge of the child's whereabouts, activities, and relations (r = –.24 vs. r = –.19, p < .05). Cross-sectional (r = –.23) and longitudinal studies (r = –.10) disclosed significant effect sizes. To assess publication bias, a file-drawer analysis indicated that 7,358 studies of nil effect size would be necessary to render the association of parental monitoring and reduced marijuana usage nonsignificant. Theoretical and practical implications of parental monitoring are discussed, especially issues concerning the measurement of parental monitoring and the possible utility of the construct in curtailing marijuana use.
Ten Statisticians and Their Impacts for Psychologists
Authors: Wright Daniel B.
Published: November 2009

Although psychologists frequently use statistical procedures, they are often unaware of the statisticians most associated with these procedures. Learning more about the people will aid understanding of the techniques. In this article, I present a list of 10 prominent statisticians: David Cox, Bradley Efron, Ronald Fisher, Leo Goodman, John Nelder, Jerzy Neyman, Karl Pearson, Donald Rubin, Robert Tibshirani, and John Tukey. I then discuss their key contributions and impact for psychology, as well as some aspects of their nonacademic lives.
A Role for the X Chromosome in Sex Differences in Variability in General Intelligence?
Authors: Johnson Wendy , Carothers Andrew , Deary Ian J.
Published: November 2009

There is substantial evidence that males are more variable than females in general intelligence. In recent years, researchers have presented this as a reason that, although there is little, if any, mean sex difference in general intelligence, males tend to be overrepresented at both ends of its overall distribution. Part of the explanation could be the presence of genes on the X chromosome related both to syndromal disorders involving mental retardation and to population variation in general intelligence occurring normally. Genes on the X chromosome appear overrepresented among genes with known involvement in mental retardation, which is consistent with a model we developed of the population distribution of general intelligence as a mixture of two normal distributions. Using this model, we explored the expected ratios of males to females at various points in the distribution and estimated the proportion of variance in general intelligence potentially due to genes on the X chromosome. These estimates provide clues to the extent to which biologically based sex differences could be manifested in the environment as sex differences in displayed intellectual abilities. We discuss these observations in the context of sex differences in specific cognitive abilities and evolutionary theories of sexual selection.
Commentary on “A Role for the X Chromosome in Sex Differences in Variability in General Intelligence?” (Johnson et al., 2009)
Authors: Craig Ian W. , Haworth Claire M.A. , Plomin Robert
Published: November 2009

Johnson et al.'s (2009) article highlights the role of X-chromosomal genes in general intelligence and draws attention to their potential role in explaining the observed greater variance for this trait in males and their excess at both extremes of the distribution. We note that this would result from a simple additive effect of X-linked intelligence genes and also discuss the potentially important contribution of recessive deleterious loci. The buffering effect of heterozygosity in females will be partly constrained by the skewing of X-inactivation patterns increasing the variance of females beyond what is expected. Furthermore, escape of some X-linked genes from in-activation may also be relevant to male—female variance comparisons. We also comment on the difficulty of establishing the extent to which the X chromosome is enriched for intelligence genes and point out that their estimates of the proportion of genes influencing general intelligence that might be located on the X chromosome rely on some doubtful premises, especially concerning the likely equivalence of X-linked gene action in males and females. Finally, we discuss the increasingly compelling evidence for the accumulation of genes on the X chromosome that have selective benefit to males, including those implicated infertility and some manifestations of intelligence.
Speculation to Inform and Speculation to Explore
Authors: Johnson Wendy , Carothers Andrew , Deary Ian J.
Published: November 2009

Scientific speculation is exploration, but it can also be used to inform, particularly across disciplines. This article, a follow-up to an empirical article on the same subject, was written with both of these purposes in mind. Many researchers are interested in uncovering the genetic mechanisms underlying general intelligence, so no doubt the roles of genes on the X chromosome will one day be understood. Psychologists can contribute best to these developments by being informed about the genetic issues involved.
Chronic Cortical and Subcortical Pathology with Associated Neurological Deficits Ensuing Experimental Herpes Encephalitis
Authors: Armien Anibal G. , Hu Shuxian , Little Morgan R. , Robinson Nicholas , Lokensgard James R. , Low Walter C. , Cheeran Maxim C‐J.
Published: November 2009

Long‐term neurological sequela is common among herpes simplex encephalitis (HSE) survivors. Animal models for HSE are used to investigate mechanisms of acute disease, but little has been done to model chronic manifestations of HSE. The current study presents a detailed, systematic analysis of chronic neuropathology, including characterization of topography and sequential progression of degenerative lesions and inflammation. Subsequent to intranasal HSV‐1 infection, inflammatory responses that were temporally and spatially distinct persisted in infected cortical and brain stem regions. Neutrophils were present exclusively within the olfactory bulb and brain stem regions during the acute phase of infection, while the chronic inflammation was marked by plasma cells, lymphocytes and activated microglia. The chronic lymphocytic infiltrate, cytokine production, and activated microglia were associated with the loss of cortical neuropile in the entorhinal cortex and hippocampus. Animals surviving the acute infection showed a spectrum of chronic lesions from decreased brain volume, neuronal loss, activated astrocytes, and glial scar formation to severe atrophy and cavitations of the cortex. These lesions were also associated with severe spatial memory deficits in surviving animals. Taken together, this model can be utilized to further investigate the mechanisms of neurological defects that follow in the wake of HSE.