bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse childhood experiences of persons at risk for Huntington's disease or BRCA1/2 hereditary breast/ovarian cancer
Authors: van der Meer LB , van Duijn E , Wolterbeek R , Tibben A
Published: September 2011

Van der Meer LB, van Duijn E, Wolterbeek R, Tibben A. Adverse childhood experiences of persons at risk for Huntington's disease or BRCA1/2 hereditary breast/ovarian cancer.

Huntington's disease (HD) is known to have a negative impact on family life. Offspring of HD patients may be exposed to adversity in childhood because of the parent's disease and its psychological consequences. BRCA1/2 hereditary breast and ovarian cancer (BRCA1/2) increases the risk for offspring of being exposed to parental disease or loss. Childhood adversity is associated with psychopathology and various other problems in later life. Adverse childhood experiences (ACEs) before age 16 were assessed in adults at 50% risk for HD (n = 74) or BRCA1/2 (n = 82) and in controls (n = 101), using the Negative Life Events Scale. Mean number and occurrence of ACEs were compared between groups. The odds of having experienced adversity in childhood were higher in HD offspring and BRCA1/2 offspring than in controls. HD offspring reported a higher mean number of ACEs than controls or BRCA1/2 offspring. In HD offspring, the prevalence of parental disease and parental dysfunction experienced before age 16 was higher than in controls. In BRCA1/2 offspring, the prevalence of parental loss before age 16 was higher than in controls. This study indicates that 53% of HD offspring and 45% of BRCA1/2 offspring are exposed to adversity in childhood or adolescence. The relevance of these findings for counseling in predictive testing programs, reproductive decision‐making, and child rearing matters is discussed.
Is allergy prevention realistic and beneficial?
Authors: Kjellman N.‐I. Max , Nilsson Lennart
Published: September 2011

Allergic diseases among children have shown a marked increase during the last two or three decades, despite increased awareness of possible preventive measures. Preventive efforts have focused on new‐borns and infants with a biparental history of allergy as they are at particularly high risk of developing allergic disease (40–60%). No good intervention studies have been performed in the general population, only in high‐risk families. Unfortunately, so far known risk factors can only explain a small part of the recent increase in allergic diseases. The most important recommendation for everyone is not to smoke during pregnancy and when living/working with young children. Breast milk is the best for every baby, even from an immunologic aspect. Humidity problems should be reduced in homes, day‐care centres and schools. It is probably wise not to keep furred pets indoors in homes when babies have a family history of allergy. However, the effect of such advice should be assessed, including the acceptability, compliance, costs and effectiveness. There is no doubt that we should go on with preventive measures both in babies at high risk of allergy and also in the general population. At the same time, research should try to find even more efficient ways to reduce the current “allergy epidemic”.
Comparison of fructan dynamics in two wheat cultivars with different capacities of accumulation and remobilization under drought stress
Authors: Joudi Mehdi , Ahmadi Ali , Mohamadi Valiollah , Abbasi Alireza , Vergauwen Rudy , Mohammadi Hamid , Van den Ende Wim
Published: September 2011

Remobilization of stored carbohydrates in the stem of wheat plants is an important contributor to grain filling under drought stress (DS) conditions. A massive screening on Iranian wheat cultivars was performed based on stem dry weight changes under well‐watered and DS conditions. Two cultivars, Shole and Crossed Falat Hamun (CFH), with different fructan accumulation and remobilization behavior were selected for further studies. Water‐soluble carbohydrates (WSCs) and fructan metabolizing enzymes were studied both in the stem penultimate and in sucrose (Suc) treated, excised leaves. Under drought, CFH produced higher grain yields than Shole (412 vs 220 g m−2). Also, grain yield loss under drought was more limited in CFH than in Shole (17 vs 54%). Under drought, CFH accumulated more graminan‐type fructo‐oligosaccharides than Shole. After anthesis, fructan 6‐exohydrolase (6‐FEH; EC 3.2.1.154) activities increased more prominently than fructan 1‐exohydrolase (EC 3.2.1.153) activities during carbon remobilization. Interestingly, CFH showed higher 6‐FEH activities in the penultimate than Shole. The field experiment results suggest that the combined higher remobilization efficiency and high 6‐FEH activities in stems of wheat could contribute to grain yield under terminal drought. Similar to the penultimate, fructan metabolism differed strongly in Suc‐treated detached leaves of selected cultivars. This suggests that variation in the stem fructan among wheat cultivars grown in the field could be traced by leaf blade induction experiments.
The outcome of donor screening for Human T‐Cell Lymphotropic Virus infection in the Netherlands
Authors: Prinsze F. J. , Zaaijer H. L.
Published: September 2011

Background and Objectives  Blood donor screening reduces the infectious hazards related to blood transfusion, but the range of agents to be screened for is debatable. In 1993, the screening of all blood donations for Human T‐Cell Lymphotropic virus (HTLV) was introduced in the Netherlands. We analysed the outcome and costs of HTLV donor screening.

Methods  For the years 2001–2010, the number of HTLV infections among new and regular donors was used to estimate the prevented number of HTLV‐infected donors in the donor pool and the amount of morbidity prevented among recipients.

Results  Human T‐Cell Lymphotropic virus screening in the Netherlands detects per year on average 1·4 infected new donors and 0·5 infected regular donors. The prevalence among new donors is 30 times higher than the incidence among regular donors. Without HTLV screening, 14 HTLV‐infected donors would be donating blood, causing 0·8 to 0·007 cases of HTLV disease per year.

Conclusion  The lack of accurate estimators for infectivity and pathogenicity hampers the estimation of morbidity and mortality that HTLV‐infected transfusions would cause. Leucodepletion may be as effective as HTLV donor screening; its effect on HTLV transmission should be studied.
Seasonal Changes in the Histochemical Properties of the Olfactory Epithelium and Vomeronasal Organ in the Japanese Striped Snake, Elaphe quadrivirgata
Authors: Kondoh D. , Yamamoto Y. , Nakamuta N. , Taniguchi K. , Taniguchi K.
Published: September 2011

With 5 figures and 5 tables

Seasonal changes in the histochemical properties of the vomeronasal and olfactory epithelia of the Japanese striped snake were examined in four seasons, viz. the reproductive, pre‐hibernating, hibernating and post‐hibernating seasons. In the vomeronasal and olfactory supporting cells, secretory granules were much more abundant in the hibernating season than in the other seasons. In the vomeronasal and olfactory receptor cells, the lipofuscin granules were much fewer in the post‐hibernating season than in the other seasons. In histochemical studies with 21 lectins, several lectins stained the vomeronasal and olfactory epithelia (receptor cells, supporting cells and free border) more weakly in the hibernating season than in the reproductive season. However, all lectins stained both epithelia in the hibernating season after sialic acid removal in a similar manner as in the reproductive season after sialic acid removal. These lectin histochemical studies indicate that sialic acid residues in the vomeronasal and olfactory epithelia are more numerous in the hibernating season than in the reproductive season. The results suggest that during hibernation, the vomeronasal and olfactory receptor cells possibly undergo rapid cell turnover, and that during this time, the vomeronasal and olfactory epithelia are securely protected from pathogens by an innate immune defence system.
QTL mapping of coleorhiza length in maize (Zea mays L.) under two germination environmental conditions
Authors: Jiang Xuwen , Tian Baohua , Zhang Weimin , Wang Guoying , Wang Jianhua
Published: September 2011

With 2 figures and 3 tables

In our present study, using molecular marker technology, we aimed to identify the genetic factors controlling the length of coleorhiza during seed germination based on a population of recombinant inbred lines (RILs) derived from Xinzi517 × B73. The genetic linkage map was constructed with 255 simple sequence repeat markers, which covered 2399 cM of maize genome with an average mapping distance of 9.4 cM. We detected a total of 10 putative quantitative trait loci (QTLs) using composite interval mapping, among which six QTLs were detected on chromosomes 1, 2, 7 and 9 (10°C, 28 day), whereas four QTLs were detected on chromosomes 1, 2, 3 and 9 (25°C, 7 day). The percentage of phenotypic variance (R2) explained by QTL ranged from 5.18 to 16.67 (10°C, 28 day) and 6.73–11.46 (25°C, 7 day), respectively. These results provided the foundation for detecting additional QTL and discovering more favourable alleles for high vigour seed of maize in future study.
Identification of silverleaf whitefly resistance in pepper
Authors: Firdaus Syarifin , Van Heusden Adriaan , Harpenas Asep , Supena Ence D. J. , Visser Richard G. F. , Vosman Ben
Published: September 2011

With 4 tables

Whitefly is economically one of the most threatening pests of pepper worldwide, which is mainly caused by its ability to transmit many different viruses. In this research, we characterized pepper germplasm to identify whitefly‐resistant accessions that will form the basis for future resistance breeding. Forty‐four pepper accessions representing four species (Capsicum annuum, C. frutescens, C. chinense, C. baccatum) were screened for resistance to whiteflies. Screening parameters were adult survival (AS) and oviposition rate (OR) in a no‐choice test and whitefly, egg and nymphal density in free‐choice tests. To combine parameters in free‐choice tests, a plant resistance value was calculated. The results show that AS and OR were significantly different among accessions and were positively correlated, which was also the case for the parameters in the free‐choice tests. Accessions identified as highly resistant in no‐choice and free‐choice tests generally were C. annuum. Whitefly density and OR correlated positively with trichome density and negatively with cuticle thickness of leaves.
Paroxetine controlled‐release formulation in the treatment of major depressive disorder: A randomized, double‐blind, placebo‐controlled study in Japan and Korea
Authors: Higuchi Teruhiko , Hong Jin Pyo , Jung Hee‐Yeon , Watanabe Yoshinori , Kunitomi Taro , Kamijima Kunitoshi
Published: September 2011

Aim:  The main purpose of this study was to evaluate the efficacy of paroxetine controlled‐release (CR) formulation compared to placebo. A secondary objective was to test the hypothesis that the CR decreases selective‐serotonin‐reuptake‐inhibitors‐induced nausea as its formulation allows more distal gastrointestinal absorption than the paroxetine immediate‐release (IR) formulation.

Methods:  We conducted this study in Japanese and Korean patients with major depressive disorder (MDD) in order to demonstrate the efficacy and safety of paroxetine CR compared with placebo. The primary efficacy end‐point was the adjusted mean change from baseline in the 17‐item Hamilton Rating Scale for Depression total score at Week 8.

Results:  A total of 416 patients with MDD were randomly assigned to the CR, IR and placebo groups. The mean change from baseline in the 17‐item Hamilton Rating Scale for Depression was −12.8 in the CR group, −12.5 in the IR group, and −10.4 in the placebo group, which showed a statistically significant difference compared to placebo in CR (P < 0.001) and IR (P = 0.015). The incidence of adverse events was 65% in CR, 69% in IR and 55% in placebo. The adverse events were mostly mild or moderate in severity. In the early treatment period, when initiated from 12.5 mg, the incidence of nausea in the CR group was 6%, which was comparable with that of placebo (5%).

Conclusion:  Paroxetine CR is efficacious in the acute treatment of MDD and may have the potential benefit of decreasing the incidence of nausea in the early treatment period.
Novel molecular imaging in lung and pleural diseases
Authors: FRANCIS ROSLYN , SEGARD TATIANA , MORANDEAU LAURENCE
Published: September 2011

Molecular imaging provides an opportunity to study biological processes in vivo. Specific molecular ‘probes’ are labelled with radioactive tracers, and imaging is carried out using either PET or gamma‐cameras. The imaging is quantitative, and therefore the activity of a specific biological process (e.g. metabolism or proliferation) can be numerically assessed, which may be important for prognosis or therapy monitoring. The use of molecular imaging may lead to the development of a ‘molecular profile’ of a disease, therefore facilitating individualization of therapy and rational treatment approaches. This review article summarizes the most commonly used molecular imaging agents and their role in lung and pleural diseases. This is a rapidly developing field as new targets and imaging probes are being developed and as their clinical roles are being established.
The effect of inorganic particle concentration on bacteria–virus–nanoflagellate dynamics
Authors: Salter Ian , Böttjer Daniela , Christaki Urania
Published: September 2011

The effect of inorganic particle concentrations on bacteria–virus–nanoflagellate dynamics in an oligotrophic coastal system was investigated using a model aluminosilicate, kaolinite, with a modal size of 2.1 µm. Virus‐only, bacteria‐only and bacteria–virus–nanoflagellate incubations were carried out at increasing kaolinite concentrations to elucidate the microbial response. The sorption of bacteria and viruses to kaolinite particles was negligible over a concentration range of 1–50 mg l−1. In contrast, the abundance of heterotrophic nanoflagellates was negatively correlated with kaolinite concentrations following both 48 and 96 h incubations. Calculated nanoflagellate bacterial ingestion rates were reduced by 5–35% depending on kaolinite particle concentration. In the bacteria–virus–nanoflagellate incubations viral production increased by 56 × 103 to 104 × 103 VLPs ml−1 h−1 as a function of kaolinite particle concentration. Our results demonstrate for the first time that the interaction of microbial populations with inorganic particles can shift the balance between protist and virally mediated mortality of marine heterotrophic prokaryotes.
Accurate analysis of prevalence of coccidiosis in individually identified wild cranes in inhabiting and migrating populations in Japan
Authors: Honma Hajime , Suyama Yoshihisa , Watanabe Yuki , Matsumoto Fumio , Nakai Yutaka
Published: September 2011

Eimeria gruis and E. reichenowi cause coccidiosis, a major parasitic disease of cranes. By non‐invasive molecular approaches, we investigated the prevalence and genetic characterization of pathogens in two Japanese crane habitats; one is Hokkaido inhabited by the endangered red‐crowned crane, and the other is Izumi in Kyushu where populations that consist mainly of vulnerable hooded and white‐naped cranes migrate in winter. The non‐invasively collected faecal samples from each wintering population were first subjected to host genomic DNA‐targeted analyses to determine the sample origin and avoid sample redundancy. Extremely high prevalence was observed in the Izumi populations (> 90%) compared with the Hokkaido population (18–30%) by examining 470 specimens by microscopy and PCR‐based capillary electrophoresis (PCR‐CE), using genetic markers in the second internal transcribed spacer (ITS2). Correspondence analysis of PCR‐CE data revealed differences in community composition of coccidia between hooded and white‐naped cranes. 18S rRNA and ITS2 sequences were determined from single oocysts excreted by red‐crowned and hooded cranes. Phylogenetic analysis of 18S rRNA suggested that E. reichenowi was polyphyletic while E. gruis was monophyletic. Together with PCR‐CE data, these results indicate different host specificity among the E. reichenowi type. Our data suggest that E. reichenowi comprises multiple species.
Relationships between baroreceptor cardiac reflex sensitivity and cognitive performance: Modulations by gender and blood pressure
Authors: Reyes Del Paso Gustavo A. , Mata José luis , Martín‐Vázquez María
Published: September 2011

This study aimed at replicating and extending previous results on the association between baroreceptor reflex sensitivity (BRS) and cognitive performance. Thirty men and 31 women performed an arithmetic task. After adjusting for numerical aptitude and effort, no predictors of performance were found in men. In women, the relationships between BRS and parameters related to correct responses were modulated by blood pressure (BP). BRS was inversely associated with these parameters for participants with BP>1 SD above the mean, whereas the associations were positive in participants with BP<1 SD below the mean. Also for women, BRS was positively associated with number of errors during the task. These results suggest that the relation between BRS and performance varies as a function of the type of cognitive processes assessed and that the central nervous system effects of the baroreceptors on cognitive functioning are modulated by gender and BP.
Planning of visually guided reach‐to‐grasp movements: Inference from reaction time and contingent negative variation (CNV)
Authors: Zaepffel Manuel , Brochier Thomas
Published: September 2011

We performed electroencephalogram (EEG) recording in a precuing task to investigate the planning processes of reach‐to‐grasp movements in human. In this reaction time (RT) task, subjects had to reach, grasp, and pull an object as fast as possible after a visual GO signal. We manipulated two parameters: the hand shape for grasping (precision grip or side grip) and the force required to pull the object (high or low). Three seconds before the GO onset, a cue provided advance information about force, grip, both parameters, or no information at all. EEG data show that reach‐to‐grasp movements generate differences in the topographic distribution of the late Contingent Negative Variation (ICNV) amplitude between the 4 precuing conditions. Along with RT data, it confirms that two distinct functional networks are involved with different time courses in the planning of grip and force. Finally, we outline the composite nature of the lCNV that might reflect both high‐ and low‐level planning processes.
The role of presleep negative emotion in sleep physiology
Authors: Vandekerckhove M. , Weiss R. , Schotte C. , Exadaktylos V. , Haex B. , Verbraecken J. , Cluydts R.
Published: September 2011

Although daytime emotional stressful events are often presumed to cause sleep disturbances, the few studies of stressful life events on sleep physiology have resulted in various and contradictory findings. As research has focused in particular on stress in itself, the present study is the first to investigate the effect using polysomnography (PSG). Results indicate a significant increase in sleep fragmentation, as expressed by decreased sleep efficiency, total sleep time, percentage of rapid eye movement (REM) sleep, and an increased wake after sleep onset latency, total time awake, latency to SWS, number of awakenings and number of awakenings from REM sleep. The results demonstrate that negative emotion correlates with enhanced sleep fragmentation helping us to understand why sleep patterns change and how sleep disturbances may develop.
The effect of an antenatal physical exercise programme on maternal/perinatal outcomes and quality of life in overweight and obese pregnant women: a randomised clinical trial
Authors: Nascimento SL , Surita FG , Parpinelli MÂ , Siani S , Pinto e Silva JL
Published: September 2011

Please cite this paper as: Nascimento S, Surita F, Parpinelli M, Siani S, Pinto e Silva J. The effect of an antenatal physical exercise programme on maternal/perinatal outcomes and quality of life in overweight and obese pregnant women: a randomised clinical trial. BJOG 2011;118:1455–1463.

Objective  To evaluate the effectiveness and safety of physical exercise in terms of maternal/perinatal outcomes and the perception of quality of life (QoL) in pregnant obese and overweight women.

Design  A randomised controlled clinical trial.

Setting  The Prenatal Outpatient Clinic of the Women’s Integral Healthcare Centre (CAISM‐UNICAMP) at the University of Campinas, Campinas, Brazil.

Population  Eighty‐two pregnant women (age ≥ 18 years; pre‐gestational body mass index ≥ 26 kg/m2; gestational age 14–24 weeks).

Methods  Women were randomised into two groups: women in one group exercised under supervision and received home exercise counselling (the ‘study group’; n = 40) and women in the other group followed the routine prenatal care programme (the ‘control group’; n = 42).

Main outcome measures  Primary outcomes were gestational weight gain during the programme and excessive maternal weight gain. Secondary outcomes were increased arterial blood pressure, perinatal outcomes and QoL (WHOQOL‐BREF).

Results  In the study group, 47% of pregnant women had weight gains above the recommended limit, compared with 57% of women in the control group (P = 0.43). There was no difference in gestational weight gain between the groups. Overweight pregnant women who exercised gained less weight during the entire pregnancy (10.0 ± 1.7 kg versus 16.4 ± 3.9 kg, respectively; P = 0.001) and after entry into the study (5.9 ± 4.3 kg versus 11.9 ± 1.5 kg, respectively; P = 0.021) compared with women in the control group. Arterial blood pressure was similar between the groups over time. There was no difference in perinatal outcome or QoL.

Conclusions  The exercise programme was not associated with control of gestational weight gain in our sample as a whole, but was beneficial for lower gestational weight gain in overweight women. Exercise was not associated with adverse perinatal outcomes and did not affect variation in arterial blood pressure or the perception of QoL.
Can visual cervical screening be sustained in routine health services? Experience from Mali, Africa
Authors: Teguete I , Muwonge R , Traore CB , Dolo A , Bayo S , Sankaranarayanan R
Published: September 2011

Please cite this paper as: Teguete I, Muwonge R, Traore C, Dolo A, Bayo S, Sankaranarayanan R. Can visual cervical screening be sustained in routine health services? Experience from Mali, Africa. BJOG 2012;119:220–226.

Objective  To assess the feasibility of sustaining visual cervical screening and treatment services in Mali, and to evaluate their performance and impact in improving the provision of cervical cancer control, following an initial cross‐sectional study.

Design  Descriptive study.

Setting  Bamako area, Mali.

Population  Women aged 30–59 years.

Methods  Routine visual screening and treatment services were organised through two hospitals and 14 health centres. Patients with positive visual screening tests underwent colposcopy and/or directed biopsies, and ablative or surgical excision treatment was offered to those with cervical intraepithelial neoplasia (CIN).

Main outcome measures  Test positivity, detection and treatment rates for CIN and the sustainability of screening services.

Results  Of the 14 141 women screened, 1682 (11.9%) were positive and were referred for further investigations and treatment. Over 75% of the screen‐positive women underwent colposcopy and/or biopsy. CIN 1 was detected in 383 women, CIN 2 in 88, CIN 3 in 37 and invasive cervical cancer in 497. More than 80% of women with CIN and 35% of those with invasive cancer received treatment. The test performance characteristics and treatment coverage of routine screening were similar to those observed in the preceding cross‐sectional study.

Conclusion  Visual screening and treatment services are sustainable and effective in improving cervical cancer control provision by health services in Bamako, Mali. It is essential to organise and sustain several point‐of‐care services in order to extend cervical cancer prevention in low‐income African countries.
Retinoic acid influences neuronal migration from the ganglionic eminence to the cerebral cortex
Authors: Crandall James E. , Goodman Timothy , McCarthy Deirdre M. , Duester Gregg , Bhide Pradeep G. , Dräger Ursula C. , McCaffery Peter
Published: September 2011

J. Neurochem. (2011) 119, 723–735.

The ganglionic eminence contributes cells to several forebrain structures including the cerebral cortex, for which it provides GABAergic interneurons. Migration of neuronal precursors from the retinoic‐acid rich embryonic ganglionic eminence to the cerebral cortex is known to be regulated by several factors, but retinoic acid has not been previously implicated. We found retinoic acid to potently inhibit cell migration in slice preparations of embryonic mouse forebrains, which was reversed by an antagonist of the dopamine‐D2 receptor, whose gene is transcriptionally regulated by retinoic acid. Histone‐deacetylase inhibitors, which amplify nuclear receptor‐mediated transcription, potentiated the inhibitory effect of retinoic acid. Surprisingly, when retinoic acid signalling was completely blocked with a pan‐retinoic acid receptor antagonist, this also decreased cell migration into the cortex, implying that a minimal level of endogenous retinoic acid is necessary for tangential migration. Given these opposing effects of retinoic acid in vitro, the in vivo contribution of retinoic acid to migration was tested by counting GABAergic interneurons in cortices of adult mice with experimental reductions in retinoic acid signalling: a range of perturbations resulted in significant reductions in the numerical density of some GABAergic interneuron subpopulations. These observations suggest functions of retinoic acid in interneuron diversity and organization of cortical excitatory–inhibitory balance.
The changing geographies of foreign aid and development cooperation: contributions from gift theory
Authors: Mawdsley Emma
Published: September 2011

This paper critically evaluates the ways in which Southern development actors, such as India and China, discursively construct the ‘aid’ element of South–South development cooperation. It draws upon gift theory, something that has previously been confined to analyses of Western foreign aid. Four characteristic features of the symbolic regime of South–South development cooperation are identified: the assertion of a shared ‘developing country’ identity; expertise in appropriate development; rejection of hierarchical ‘donor–recipient’ relations; and an insistence on mutual opportunity. All of these set up the positive moral valence of reciprocity, something that stands in contrast to the hegemonic public construction (if not the reality) of Western foreign aid as unreciprocated charity to the less fortunate. The paper then examines what this symbolic regime might seek to ‘euphemise’ or obscure in the realpolitik of South–South relations, including inattention to the contested sub‐national politics of ‘development’, and the growing differences amongst the G77 nations. The paper is concerned with the ways in which Southern development actors represent a challenge to the dominant aid paradigm, transgressing dominant cultural categories and social hierarchies of who gives and who receives; but it refuses to take claims of South–South solidarity and mutual benefit at face value. It concludes with some brief reflections on the implications of the emerging visibility and power of the Southern development partners for critical ‘development’ geography.
Small molecule chemokine mimetics suggest a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3
Authors: Nedjai Belinda , Li Hubert , Stroke Ilana L , Wise Emma L , Webb Maria L , Merritt J Robert , Henderson Ian , Klon Anthony E , Cole Andrew G , Horuk Richard , Vaidehi Nagarajan , Pease James E
Published: September 2011

BACKGROUND AND PURPOSE

The chemokine receptor CXCR3 directs migration of T‐cells in response to the ligands CXCL9/Mig, CXCL10/IP‐10 and CXCL11/I‐TAC. Both ligands and receptors are implicated in the pathogenesis of inflammatory disorders, including atherosclerosis and rheumatoid arthritis. Here, we describe the molecular mechanism by which two synthetic small molecule agonists activate CXCR3.

EXPERIMENTAL APPROACH

As both small molecules are basic, we hypothesized that they formed electrostatic interactions with acidic residues within CXCR3. Nine point mutants of CXCR3 were generated in which an acidic residue was mutated to its amide counterpart. Following transient expression, the ability of the constructs to bind and signal in response to natural and synthetic ligands was examined.

KEY RESULTS

The CXCR3 mutants D112N, D195N and E196Q were efficiently expressed and responsive in chemotaxis assays to CXCL11 but not to CXCL10 or to either of the synthetic agonists, confirmed with radioligand binding assays. Molecular modelling of both CXCL10 and CXCR3 suggests that the small molecule agonists mimic a region of the ‘30s loop’ (residues 30–40 of CXCL10) which interacts with the intrahelical CXCR3 residue D112, leading to receptor activation. D195 and E196 are located in the second extracellular loop and form putative intramolecular salt bridges required for a CXCR3 conformation that recognizes CXCL10. In contrast, CXCL11 recognition by CXCR3 is largely independent of these residues.

CONCLUSION AND IMPLICATIONS

We provide here a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3. Such findings may have implications for the design of CXCR3 antagonists.

LINKED ARTICLE

This article is commented on by O'Boyle, pp. 895–897 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01759.x
Functional selectivity of central Gα‐subunit proteins in mediating the cardiovascular and renal excretory responses evoked by central α2‐adrenoceptor activation in vivo
Authors: Wainford RD , Kapusta DR
Published: September 2011

BACKGROUND AND PURPOSE Activation of brain α2‐adrenoceptors in conscious rodents decreases heart rate (HR) and mean arterial blood pressure (MAP) and increases urine output and urinary sodium excretion. In vitro, α2‐adrenoceptor stimulation activates Gαi(1–3), Gαo and Gαs‐subunit protein‐gated signal transduction pathways. Here we have investigated whether these same Gα‐subunit protein‐gated pathways mediate the cardiovascular and renal excretory responses to central α2‐adrenoceptor activation in conscious Sprague‐Dawley rats.

EXPERIMENTAL APPROACH Rats were pre‐treated by intracerebroventricular injection (i.c.v.) with an oligodeoxynucleotide (ODN) targeted to a Gαi1, Gαi2, Gαi3, Gαo, Gαs or a scrambled (SCR) ODN sequence (25 µg, 24 h). On the day of study, the α2‐adrenoceptor agonist guanabenz (50 µg) or saline vehicle, was injected i.c.v. into ODN‐pre‐treated conscious rats. MAP and HR were recorded, and urine was collected for 150 min.

KEY RESULTS In vehicle‐ and SCR ODN‐pre‐treated rats, i.c.v. guanabenz decreased MAP and HR, and produced marked diuretic and natriuretic responses. Selective ODN‐mediated down‐regulation of brain Gαi2‐subunit proteins abolished the central guanabenz‐induced hypotension and natriuresis. In contrast, following selective Gαs down‐regulation, the characteristic hypotensive response to i.c.v. guanabenz was converted to an immediate increase in MAP. The bradycardic and diuretic responses to i.c.v. guanabenz were not blocked by pre‐treatment with any ODN.

CONCLUSIONS AND IMPLICATIONS There was functional selectivity of Gαi2 and Gαs subunit protein‐gated signal transduction pathways in mediating the hypotensive and natriuretic, but not bradycardic or diuretic, responses evoked by central α2‐adrenoceptor activation in vivo.
The Biometric Measurement of Alcohol Consumption
Authors: Snell Lawrence D. , Ramchandani Vijay A. , Saba Laura , Herion David , Heilig Markus , George David T. , Pridzun Lutz , Helander Anders , Schwandt Melanie L. , Phillips Monte J. , Hoffman Paula L. , Tabakoff Boris ,   and the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence Investigators
Published: September 2011

Background:  Proper ascertainment of the history of alcohol consumption by an individual is an important component of medical diagnosis of disease and influences the implementation of appropriate treatment strategies that include prescription of medication, as well as intervention for the negative physical and social consequences of hazardous/harmful levels of alcohol consumption. Biological (biometric) diagnostic tests that provide information on current and past quantity and frequency of alcohol consumption by an individual, prior to onset of organ damage, continue to be sought.

Methods:  Platelet monoamine oxidase B (MAO‐B) protein was quantitated in 2 populations of subjects who had histories of different levels of alcohol consumption. Levels were assayed by immunoblotting or by ELISA. The development and evaluation of the new ELISA‐based measure of platelet MAO‐B protein levels is described.

Results:  One subject population constituted a nontreatment‐seeking, cross‐sectional subject sample, and the other population was a longitudinally followed, hospitalized group of subjects. An algorithm combining measures of platelet MAO‐B protein with the plasma levels of carbohydrate‐deficient transferrin (CDT) and with liver enzymes (aspartate aminotransferase or γ‐glutamyltransferase [GGT]) can detect hazardous/harmful alcohol use (HHAU) with the highest sensitivity and specificity in the cross‐sectional nontreatment‐seeking population. In the treatment‐seeking population, low MAO‐B protein levels at admission are associated with heavy drinking prior to admission, and these protein levels increase over a period of abstinence from alcohol.

Conclusions:  The platelet MAO‐B protein measurement is particularly effective for male alcohol consumers. The combined use of MAO‐B protein measures together with measures of CDT and GGT does, however, improve the diagnostic utility of both markers for ascertaining HHAU in women. Furthermore, measurement of changes in platelet MAO‐B protein levels during treatment for alcohol dependence may help monitor the success of the treatment program.
Reward and Relapse: Complete Gene‐Induced Dissociation in an Animal Model of Alcohol Dependence
Authors: Quintanilla María E. , Tampier Lutske , Karahanian Eduardo , Rivera‐Meza Mario , Herrera‐Marschitz Mario , Israel Yedy
Published: September 2011

Background:  In animal models of continuous alcohol self‐administration, in which physical dependence does not constitute the major factor of ethanol intake, 2 factors likely contribute to the perpetuation of alcohol self‐administration: (i) the rewarding effects of ethanol and (ii) the contextual conditioning cues that exist along with the process of self‐administration. Present studies are aimed at understanding the relative contribution of these factors on the perpetuation of heavy alcohol self‐administration, as an indication of relapse.

Methods:  Wistar‐derived UChB high ethanol drinker rats were allowed access to 10% ethanol and water on a 24‐hour basis. In initial studies, an anticatalase shRNA gene‐coding lentiviral vector aimed at inhibiting acetaldehyde generation was administered into the ventral tegmental area (VTA) of the animals prior to ethanol access. In subsequent studies, the lentiviral vector was administered to animals, which had consumed ethanol on a 24‐hour basis, or a 1‐hour basis, after the animals had reached high levels of ethanol intake for 60 to 80 days. In final studies, quinine (0.01%) was added to the ethanol solution to alter the conditioning taste/smell cues of alcohol that animals had chronically ingested.

Results:  Data indicate that the administration of an anticatalase vector into the VTA of naïve animals blocked reward and alcohol self‐administration, while it was, nevertheless, inactive in inhibiting alcohol self‐administration in rats that had been conditioned to ingest ethanol for over 2 months. The lack of inhibitory effect of the anticatalase vector on ethanol intake in animals that had chronically self‐administered ethanol was fully reversed when the contextual conditioning cues of the alcohol solution were changed.

Conclusions:  Data highlight the importance of conditioning factors in relapse and suggest that only abolishing or blunting it, along with long‐lasting pharmacological treatment to reduce ethanol reward, may have protracted effects in reducing alcohol self‐administration.
Corticotropin‐Releasing Factor Acting on Corticotropin‐Releasing Factor Receptor Type 1 is Critical for Binge Alcohol Drinking in Mice
Authors: Kaur Simranjit , Li Ju , Stenzel‐Poore Mary P. , Ryabinin Andrey E.
Published: September 2011

Background:  The corticotropin‐releasing factor (CRF) system has been implicated in the regulation of alcohol consumption. However, previous mouse knockout (KO) studies using continuous ethanol access have failed to conclusively confirm this. Recent studies have shown that CRF receptor type 1 (CRFR1) antagonists attenuate alcohol intake in the limited access “drinking in the dark” (DID) model of binge drinking. To avoid the potential nonspecific effects of antagonists, in this study, we tested alcohol drinking in CRFR1, CRFR2, CRF, and urocortin 1 (Ucn1) KO and corresponding wild‐type (WT) littermates using the DID paradigm.

Methods:  On days 1 to 3, the CRFR1, CRFR2, Ucn1, and CRF KO mice and their respective WT littermates were provided with 20% ethanol or 10% sucrose for 2 hours with water available at all other times. On day 4, access to ethanol or sucrose was increased to 4 hours. At the end of each drinking session, the volume of ethanol consumed was recorded, and at the conclusion of the last session, blood was also collected for blood ethanol concentration (BEC) analysis.

Results:  CRFR1 KO mice had lower alcohol intakes and BECs and higher intakes of sucrose compared with WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had similar alcohol intakes on days 2 to 4 and similar BECs as the WTs. To determine the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1 KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced alcohol consumption and lower BECs compared with WTs.

Conclusions:  Our results confirm that CRFR1 plays a key role in binge drinking and identify CRF as the ligand critically involved in excessive alcohol consumption.
Alcohol Dehydrogenase‐1B Arg47His Polymorphism and Upper Aerodigestive Tract Cancer Risk: A Meta‐Analysis Including 24,252 Subjects
Authors: Guo Haipeng , Zhang Guohong , Mai Ruiqin
Published: September 2011

Background:  Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus, account for approximately 4% of all new cancers in world. Alcohol drinking is an established risk factor for UADT cancers, and the rate of alcohol metabolism could significantly been influenced by genetic polymorphisms of alcohol dehydrogenase‐1B (ADH1B) His47Arg (rs1229984). To evaluate whether combined evidence shows ADH1B His47Arg as a common genetic variant that influenced the risk of UADT cancers, we considered all available studies in a meta‐analysis.

Methods:  Eighteen studies were combined representing data of 8,539 cases and 15,713 controls for meta‐analysis. Stratified analyses were carried out to determine the gene–environment interaction between ADH1B His47Arg and alcohol drinking and gene–gene interaction between ADH1B His47Arg and aldehyde dehydrogenase‐2 (ALDH2) Glu/Lys related to UADT cancer risk. Potential sources of heterogeneity between studies were explored; sensitivity analysis and publication bias was also evaluated.

Results:  The ADH1B 47Arg allele was found to be associated with increased risk of UADT cancers, the pooled odds ratios (ORs) being 1.66 (95% CI: 1.54 to 1.79) and 3.47 (95% CI: 2.76 to 4.36) for the His/Arg and Arg/Arg genotypes compared with the His/His genotype, respectively. An 18.48‐fold increase in OR (95% CI: 12.95 to 26.40) for UADT cancers among alcohol drinkers with Arg/Arg genotype was found, when compared among nondrinkers with the His/His genotype. Significant interaction between carriers with ADH1B 47Arg and ALDH2 487Lys allele related to risk for UADT cancers was more evident, compared with noncarriers (OR = 10.31, 95% CI: 5.45 to 18.85).

Conclusions:  ADH1B 47Arg allele is a common genetic variant that increased the risk of UADT cancers; furthermore, it modulates the susceptibility to UADT cancers coupled with alcohol drinking and interaction with the ALDH2 487Lys allele.
GABAA Receptor Modulation During Adolescence Alters Adult Ethanol Intake and Preference in Rats
Authors: Hulin Mary W. , Amato Russell J. , Winsauer Peter J.
Published: September 2011

Background:  To address the hypothesis that GABAA receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABAA receptor modulator on adult alcohol intake and preference were assessed.

Methods:  Three groups of adolescent male rats received 12 injections of lorazepam (3.2 mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days starting on postnatal day (PD) 35. After this time, the doses were increased to 5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days. Subjects had access to 25 to 30 g of food daily, during the period of the first 6 injections, and 18 to 20 g thereafter. Food intake of each group was measured 60 minutes after food presentation, which occurred immediately after drug administration on injection days or at the same time of day on noninjection days. When subjects reached adulthood (PD 88), ethanol preference was determined on 2 separate occasions, an initial 3‐day period and a 12‐day period, in which increasing concentrations of ethanol were presented. During each preference test, intake of water, saccharin, and an ethanol/saccharin solution was measured after each 23‐hour access period.

Results:  During adolescence, lorazepam increased 60‐minute food intake, and this effect was enhanced under the more restrictive feeding schedule. DHEA had the opposite effect on injection days, decreasing food intake compared with noninjection days. In adulthood, the lorazepam‐treated group preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin alone compared with vehicle‐treated subjects, which showed no preference for any concentration of ethanol/saccharin over saccharin. DHEA‐treated subjects showed no preference among the 3 solutions.

Conclusions:  These data demonstrate that GABAA receptor modulation during adolescence can alter intake and preference for ethanol in adulthood and highlights the importance of drug history as an important variable in the liability for alcohol abuse.
The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene (OPRM1) on Alcoholism Etiology and Treatment: A Critical Review
Authors: Ray Lara A. , Barr Christina S. , Blendy Julie A. , Oslin David , Goldman David , Anton Raymond F.
Published: September 2011

The endogenous opioid system has been implicated in the pathophysiology of alcoholism as it modulates the neurobehavioral effects of alcohol. A variant in the mu opioid receptor gene (OPRM1), the Asn40Asp polymorphism, has received attention as a functional variant that may influence a host of behavioral phenotypes for alcoholism as well as clinical response to opioid antagonists. This paper will review converging lines of evidence on the effect of the Asn40Asp SNP on alcoholism phenotypes, including: (i) genetic association studies; (ii) behavioral studies of alcoholism; (iii) neuroimaging studies; (iv) pharmacogenetic studies and clinical trials; and (v) preclinical animal studies. Together, these lines of research seek to elucidate the effects of this functional polymorphism on alcoholism etiology and treatment response.
Mineral Carbonation as the Core of an Industrial Symbiosis for Energy‐Intensive Minerals Conversion
Authors: Brent Geoffrey F. , Allen Daniel J. , Eichler Brent R. , Petrie James G. , Mann Jason P. , Haynes Brian S.
Published: September 2011

The longer term sustainability of the minerals sector may hinge, in large part, on finding innovative solutions to the challenges of energy intensity and carbon dioxide (CO2) management. This article outlines the need for large‐scale “carbon solutions” that might be shared by several colocated energy‐intensive and carbon‐intensive industries. In particular, it explores the potential for situating a mineral carbonation plant as a carbon sink at the heart of a minerals and energy complex to form an industrial symbiosis. Several resource‐intensive industries can be integrated synergistically in this way, to enable a complex that produces energy and mineral products with low net CO2 emissions. An illustrative hypothetical case study of such a system within New South Wales, Australia, has been constructed, on the basis of material and energy flows derived from Aspen modeling of a serpentine carbonation process. The synergies and added value created have the potential to significantly offset the energy and emission penalties and direct costs of CO2 capture and storage. This suggests that greenfield minerals beneficiation and metals refining plants should consider closer integration with the power production and energy provision plants on which they depend, together with a carbon solution, such as mineral carbonation, as a critical element of such integration. Other sustainability considerations are highlighted.
Simon Patten on Public Infrastructure and Economic Rent Capture
Authors: HUDSON MICHAEL
Published: September 2011

Abstract

Reflecting the Progressive Era's reform agenda Simon Patten (1852–1922) argued that freeing markets from one source of economic rent (by taxing land rent) would merely leave the surplus to be taken by other monopolists and rent extractors (railroads, Wall Street trusts, and basic privatized utilities). To prevent unearned income (economic rent) from adding to the economy's cost of living and doing business, potentially rent‐yielding infrastructure should be kept in the public domain as a “fourth factor of production.” Instead of rentiers making a profit by charging access fees and user fees, the return to public investment should take the form of reducing the economy's overall price structure.
Does the Lack of a Profit Motive Affect Hiring in Academe? Evidence from the Market for Lawyers
Authors: PJESKY REX J. , SUTTER DANIEL
Published: September 2011

Abstract

The comparative performance of academic and economic markets continues to be debated. One factor potentially distinguishing academic markets is the profit motive. Profit and competition have been shown to curb discrimination in markets, and the absence of profit discipline could result in myriad forms of prejudice in academic hiring. We explore the role of the profit motive in the performance of academic markets by comparing the pedigree of employees of top law schools and top law firms. Top law schools are much more likely to employ graduates of top ranked law schools than elite law firms, and the difference exists at both the junior and senior levels. We find no evidence that the graduates of top 5 law schools outperform grads of less prestigious schools in publications or citations. In the absence of a profit motive, academic hiring appears more likely to indulge a preference for pedigree, and by implication, this may explain other scholarly prejudices in the academy.