bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of starlings in the spread of Salmonella within concentrated animal feeding operations
Authors: Carlson James C. , Franklin Alan B. , Hyatt Doreene R. , Pettit Susan E. , Linz George M.
Published: December 2010

1. Characterizing and mitigating the disease risks associated with wildlife use of concentrated animal feeding operations (CAFOs) can reduce the spread of micro‐organisms throughout the environment while increasing agricultural productivity. To better understand the disease risks associated with bird use of CAFOs, we assessed the capacity of European starlings Sturnus vulgaris to spread Salmonella enterica to cattle, their feed and water.

2. We sampled starlings, cattle feed, cattle water and cattle faeces from 10 CAFOs in Texas, USA. Samples were screened for Salmonella enterica to investigate: (i) the prevalence of S. enterica in starlings using CAFOs, (ii) whether there was a relationship between cattle infections and starling numbers, and (iii) if S. enterica contamination of cattle feed and water was related to numbers of starlings observed on CAFOs.

3. We used generalized linear mixed logistic regression models to assess the importance of starlings, cattle stocking, facility management and environmental variables in the transmission of S. enterica to cattle, feed troughs and water troughs in CAFOs.

4. Starling gastrointestinal tract samples tested positive for S. enterica (2·5% prevalence; 95% CI = 0·3%, 8·6%) and starlings were retained as model covariates in the best supported logistic regression models for S. enterica contamination within cattle feed, water and faeces.

5. Salmonella enterica contamination of both cattle feed troughs and water troughs is significantly related to numbers of starlings. Contamination in cattle feed increased as more starlings entered feed troughs. Contamination in water troughs increased asymptotically as numbers of starlings on CAFOs increased. Starling variables in the cattle faecal shedding model were not significant.

6. Synthesis and applications. The numbers of European starlings better explained S. enterica contamination of cattle feed and water than other variables including cattle stocking, facility management and environmental variables. This suggests that starlings are a source of S. enterica contamination in CAFOs. Thus, starling management tools such as population control, habitat management, exclusionary devises and bird repellents may be used to reduce the amplification and spread of disease within livestock production systems.
Virulence in Trypanosoma congolense Savannah subgroup. A comparison between strains and transmission cycles
Authors: VAN den BOSSCHE P. , CHITANGA S. , MASUMU J. , MARCOTTY T. , DELESPAUX V.
Published: December 2010

Trypanosoma congolense strains have been shown to differ in their virulence both between subgroups and within the Savannah subgroup between strains. This review revisits these findings and complements them with information on the virulence of T. congolense Savannah subgroup strains isolated from cattle (domestic transmission cycle) in different geographical areas and of strains isolated in protected areas where trypanotolerant wildlife species are the reservoir of the trypanosomes (sylvatic transmission cycle). The virulence of a total of 62 T. congolense Savannah subgroup strains (50 domestic and 12 sylvatic), determined using a standard protocol in mice, was compared. Virulence varied substantially between strains with, depending on the strain, the median survival time of infected mice varying from five to more than sixty days. The proportion of highly virulent strains (median survival time <10 days) was significantly (P = 0·005) higher in strains from the sylvatic transmission cycle. The analysis highlights repercussions of the domestication of the trypanosomiasis transmission cycle that may have to be taken in consideration in the development of trypanosomiasis control strategies.
AtNUFIP, an essential protein for plant development, reveals the impact of snoRNA gene organisation on the assembly of snoRNPs and rRNA methylation in Arabidopsis thaliana
Authors: Rodor Julie , Jobet Edouard , Bizarro Jonathan , Vignols Florence , Carles Cristel , Suzuki Takamasa , Nakamura Kenzo , Echeverría Manuel
Published: December 2010

In all eukaryotes, C/D small nucleolar ribonucleoproteins (C/D snoRNPs) are essential for methylation and processing of ribosomal RNAs. They consist of a box C/D small nucleolar RNA (C/D snoRNA) associated with four highly conserved nucleolar proteins. Recent data in HeLa cells and yeast have revealed that assembly of these snoRNPs is directed by NUFIP protein and other auxiliary factors. Nevertheless, the precise function and biological importance of NUFIP and the other assembly factors remains unknown. In plants, few studies have focused on RNA methylation and snoRNP biogenesis. Here, we identify and characterise the AtNUFIP gene that directs assembly of C/D snoRNP. To elucidate the function of AtNUFIP in planta, we characterized atnufip mutants. These mutants are viable but have severe developmental phenotypes. Northern blot analysis of snoRNA accumulation in atnufip mutants revealed a specific degradation of C/D snoRNAs and this situation is correlated with a reduction in rRNA methylation. Remarkably, the impact of AtNUFIP depends on the structure of snoRNA genes: it is essential for the accumulation of those C/D snoRNAs encoded by polycistronic genes, but not by monocistronic or tsnoRNA genes. We propose that AtNUFIP controls the kinetics of C/D snoRNP assembly on nascent precursors to overcome snoRNA degradation of aberrant RNPs. Finally, we show that AtNUFIP has broader RNP targets, controlling the accumulation of scaRNAs that direct methylation of spliceosomal snRNA in Cajal bodies.
Multiple cytosolic and transmembrane determinants are required for the trafficking of SCAMP1 via an ER–Golgi–TGN–PM pathway
Authors: Cai Yi , Jia Tianran , Lam Sheung Kwan , Ding Yu , Gao Caiji , San Melody Wan Yan , Pimpl Peter , Jiang Liwen
Published: December 2010

How polytopic plasma membrane (PM) proteins reach their destination in plant cells remains elusive. Using transgenic tobacco BY‐2 cells, we previously showed that the rice secretory carrier membrane protein 1 (SCAMP1), an integral membrane protein with four transmembrane domains (TMDs), is localized to the PM and trans‐Golgi network (TGN). Here, we study the transport pathway and sorting signals of SCAMP1 by following its transient expression in tobacco BY‐2 protoplasts and show that SCAMP1 reaches the PM via an endoplasmic reticulum (ER)–Golgi–TGN–PM pathway. Loss‐of‐function and gain‐of‐function analysis of various green fluorescent protein (GFP) fusions with SCAMP1 mutations further demonstrates that: (i) the cytosolic N‐terminus of SCAMP1 contains an ER export signal; (ii) the transmembrane domain 2 (TMD2) and TMD3 of SCAMP1 are essential for Golgi export; (iii) SCAMP1 TMD1 is essential for TGN‐to‐PM targeting; (iv) the predicted topology of SCAMP1 and its various mutants remain identical as demonstrated by protease protection assay. Therefore, both the cytosolic N‐terminus and TMD sequences of SCAMP1 play integral roles in mediating its transport to the PM via an ER–Golgi–TGN pathway.
A small molecule with differential effects on the PTS1 and PTS2 peroxisome matrix import pathways
Authors: Brown Laura‐Anne , O’Leary‐Steele Catherine , Brookes Paul , Armitage Lynne , Kepinski Stefan , Warriner Stuart L. , Baker Alison
Published: December 2010

The use of small molecules has great power to dissect biological processes. This study presents the identification and characterisation of an inhibitor of peroxisome matrix protein import. A mini‐screen was carried out to identify molecules that cause alteration in peroxisome morphology, or mislocalization of a peroxisome targeted fluorescent reporter protein. A benzimidazole lead compound (LDS‐003655) was identified that resulted in reduced GFP fluorescence in peroxisomes and cytosolic GFP accumulation. The effect of the compound was specific to peroxisomes as Golgi bodies, endoplasmic reticulum and the actin cytoskeleton were unaffected even at 25 μm, whereas peroxisome import via the PTS1 pathway was compromised at 100 nm. When seedlings were grown on 25 μm LDS‐003655 they displayed morphology typical of seedlings grown in the presence of auxin, and expression of the auxin reporter DR5::GFP was induced. Analysis of a focussed library of LDS‐003655 derivatives in comparison with known auxins led to the conclusion that the auxin‐like activity of LDS‐003655 is attributable to its in situ hydrolysis giving rise to 2,5‐dichlorobenzoic acid, whereas the import inhibiting activity of LDS‐003655 requires the whole molecule. None of the auxins tested had any effect on peroxisome protein import. Matrix import by the PTS2 import pathway was relatively insensitive to LDS‐003655 and its active analogues, with effects only seen after prolonged incubation on high concentrations. Steady‐state protein levels of PEX5, the PTS1 import pathway receptor, were reduced in the presence of 100 nm LDS‐003655, suggesting a possible mechanism for the import inhibition.
A practical, algorithmic approach to diagnosing hair shaft disorders
Authors: Mirmirani Paradi , Huang Kathie P. , Price Vera H.
Published: December 2010

The hair shaft is a unique structure composed of an inner cortex and a protective outer cuticle. Any defects in this normal structure due to genetics or the environment can lead to variations in physical properties. Thus one should suspect a hair shaft disorder if a patient presents with an abnormality or change in hair texture, appearance, manageability or ability to grow hair long. A key feature of the clinical evaluation is to determine whether there is hair breakage (increased fragility) by looking for broken hairs and performing a tug test. Once this determination is made, an algorithmic approach can be used to narrow the differential diagnosis: hair shaft disorders with and without fragility. A hair mount along with other directed questions and examination will almost always allow the clinician to make an in‐office diagnosis. Common case scenarios, photographs, and practical tips are provided to illustrate the use of this algorithmic approach in the diagnosis of hair shaft disorders. We have also included a summary of the molecular defects where known, which can be helpful in providing a correlation with clinical findings, in counseling patients, and potentially offering treatment options.
Visuospatial impairment in children and adolescents after liver transplantation
Authors: Haavisto Anu , Korkman Marit , Törmänen Jussi , Holmberg Christer , Jalanko Hannu , Qvist Erik
Published: December 2010

Haavisto A, Korkman M, Törmänen J, Holmberg C, Jalanko H, Qvist E. Visuospatial impairment in children and adolescents after liver transplantation. Pediatr Transplantation 2011: 15:184–192. © 2010 John Wiley & Sons A/S.

Abstract:  A minority of children with liver transplants exhibit significant delay in global intelligence; others have specific learning disabilities. More specific data on neurocognitive strengths and weaknesses are lacking. Eighteen children aged 7–16 yr, who had undergone LTx in Finland participated in the study. They were assessed on an average 7.6 (s.d. 4.5, range 1.0–15.0) years post‐operatively at a mean age of 11.8 (s.d. 3.1, range 7.2–16.1). A standardized test of intelligence (WISC‐III), a neuropsychological test battery (NEPSY‐II), and a parental questionnaire on the child’s development (FTF) were administered. The neuropsychological test profile of the LTx group was compared with that of a matched control group of healthy children. The LTx children achieved on an average normal FSIQ 94.0 and VIQ 99.6. Their Performance Intelligence Quotient (PIQ 88.9, p = 0.043) was, however, significantly lower than the population mean. On neuropsychological assessment, the LTx children scored generally lower than the control group (p = 0.004), a difference significant in sub‐tests assessing visuospatial and visuoconstructive functions and social perception. No differences emerged in sub‐tests of attention and executive functions, memory and learning, or language functions. LTx children are at increased risk for impairment in the visuospatial domain.
Seasonal variation of leaf respiration and the alternative pathway in field‐grown Populus×canadensis
Authors: Searle Stephanie Y. , Turnbull Matthew H.
Published: December 2010

The temperature response of plant respiration varies between species and can acclimate to changing temperatures. Mitochondrial respiration in plants has two terminal oxidases: the cytochrome c oxidase (COX) and the cyanide‐resistant alternative oxidase (AOX). In Populus×canadensis var. italica, a deciduous tree species, we investigated the temperature response of leaf respiration via the alternative and cytochrome pathways, as well as seasonal changes in these pathways, using the oxygen isotope fractionation technique. The electron partitioning through the alternative pathway (τa) increased from 0 to 30–40% with measurement temperatures from 6 to 30°C at all times measured throughout the growing season. τa at the growth temperature (the average temperature during 3 days prior to sampling) increased from 12 to 29% from spring until late summer and decreased thereafter. Total respiration declined throughout the growing season by 50%, concomitantly with decreases in both AOX (64%) and COX (32%) protein abundances. Our results provide new insight into the natural variability of AOX protein abundances and alternative respiration electron partitioning over immediate and seasonal timescales.
The Western Pacific Regional Child Survival Strategy: Progress and challenges in implementation
Authors: Jayawardena Nelu , Subhi Rami , Duke Trevor
Published: December 2010

The Regional Child Survival Strategy (RCSS) was launched by the World Health Organization and United Nations Children's Fund in 2006. This initially involved the six highest mortality burden countries in the region (Cambodia, China, Laos PDR, Papua New Guinea, Philippines and Vietnam). This paper aimed to describe the experiences of countries in the region in adopting and implementing the RCSS, and to identify factors that promote and impede progress. Child mortality has fallen substantially since 1990, and the region as a whole is on track to achieve the Millennium Development Goal 4 (MDG‐4) targets. Some countries have made slower progress and are struggling. There is an urgent need to support countries that have, until now, not been included in the RCSS, particularly smaller Pacific Island nations, and to provide greater support to the poorest countries if MDG‐4 targets for the region are to be achieved.
Update on attention deficit hyperactivity disorder
Authors: Efron Daryl , Hazell Philip , Anderson Vicki
Published: December 2010

Attention deficit hyperactivity disorder (ADHD) is now the most frequent diagnosis in children seen by Australian general paediatricians. It is a heterogeneous neurodevelopmental disorder and is usually accompanied by one or more co‐morbid developmental and/or mental health conditions. In addition to daily symptoms, which often impair quality of life, ADHD can compromise educational and social development for the individual, and impact on families, schools and the broader community. Draft revised National Health and Medical Research Council Guidelines on ADHD were published in November 2009. This comprehensive document discusses the evidence in relation to many aspects of ADHD, which inform the large number of practice recommendations. Although there is an enormous literature on the causes, neurobiology and management of ADHD, there is still much to be learned particularly in relation to early intervention, behavioural therapies and factors influencing long‐term outcomes.
Streptococcus pneumoniae sepsis in the newborn
Authors: Malhotra Atul , Hunt Rod W , Doherty Richard R
Published: December 2010

Background:  Streptococcus pneumoniae (SP) is an uncommon cause of neonatal sepsis.

Aims:  To report on the spectrum of morbidity associated with SP infections in the neonatal period.

Methods:  A case series of SP infection in the neonatal period was studied. Maternal and neonatal outcomes were noted.

Results:  Four cases of neonatal SP infection are reported, one of which was due to a strain with reduced susceptibility to penicillin. All four cases had very early onset of severe clinical disease with bacteremia and pneumonia. In one case a retrospective diagnosis of meningitis was made as well. Maternal illness was a feature in one of these infants.

Conclusions:  Although less common now than in the pre‐antibiotic era, Streptococcus pneumoniae remains a rare but important cause of neonatal sepsis and can mimic early onset Group B streptococcal sepsis. It is unclear whether current infant or adult pneumococcal immunisation programs might influence its incidence in the neonatal period. The potential for strains with reduced susceptibility to β‐lactam antibiotics to cause neonatal infection needs to be considered in relevant settings.
Persistence of acute rheumatic fever in a tertiary children's hospital
Authors: Smith Michael T , Lester‐Smith David , Zurynski Yvonne , Noonan Sara , Carapetis Jonathan R , Elliott Elizabeth J
Published: December 2010

Aim:  To identify and describe all children admitted with acute rheumatic fever (ARF) to a tertiary paediatric hospital in Sydney over a 9‐year period and to describe their demographic and clinical characteristics, management and short‐term outcomes. Delays in diagnosis, recurrence of ARF and use of secondary prophylaxis were also documented.

Methods:  Retrospective review of medical records for children aged <15 years admitted to the Children's Hospital at Westmead, Sydney, with ARF (International Classification of Diseases (ICD)‐10 classification I0.0–I09.9) during 2000–2008. Only cases meeting the National Heart Foundation of Australia diagnostic criteria for ARF were included.

Results:  Twenty‐six children met the National Heart Foundation of Australia criteria for ARF. The median age was 11.5 years (range 5.8–14.6) and 15 (58%) were male. Ten (38%) identified as Pacific Islander, and 5 (19%) as Aboriginal and Torres Strait Islander (ATSI). Most (n= 20, 77%) lived in suburban Sydney, and 69% were classified in the two most disadvantaged quintiles on the Index of Relative Socioeconomic Disadvantage and Advantage. Four (15%) had Sydenham's chorea, and 81% had carditis (mitral and/or aortic regurgitation). Six (23%) children had previous ARF. Antibiotic prophylaxis to prevent recurrent ARF was prescribed in all cases, but 50% received oral penicillin, rather than by intramuscular injection. Barriers to timely diagnosis were identified in 81%, including delayed presentation and delayed referral.

Conclusion:  Most children presenting to the hospital with ARF lived in disadvantaged areas of Sydney. Pacific Islander and Aboriginal and Torres Strait Islander children were over‐represented. Mitigation of RHD requires early identification of ARF and appropriate delivery of secondary prophylaxis.
Functional haplotypes in the PTGDR gene fail to associate with asthma in two Australian populations
Authors: JAMROZIK Euzebiusz F. , WARRINGTON Nicole , MCCLENAGHAN Jane , HUI Jennie , MUSK Arthur W. , JAMES Alan , BEILBY John P. , HANSEN Janice , DE KLERK Nicholas H. , PALMER Lyle J.
Published: December 2010

Background and objective:  Haplotypes in the promoter region of the prostanoid DP receptor (PTGDR) gene have been shown to functionally influence gene transcription and to be associated with asthma in two previous case–control studies in Caucasians. This study tested the association of PTGDR haplotypes with asthma phenotypes in two large Caucasian‐Australian populations. These results were incorporated in a meta‐analysis with previously published data to determine the overall role for these haplotypes in the risk of asthma.

Methods:  Three PTGDR promoter‐region single nucleotide polymorphisms (SNP) were genotyped in 368 individuals from the Western Australian Twin Child Health study and 2988 individuals from the Busselton Health Study. Logistic regression and transition disequilibrium tests were used to assess whether SNP genotypes and three SNP haplotypes were associated with doctor‐diagnosed asthma or intermediate quantitative traits. Longitudinal data from the Busselton Health Study were used to examine whether PTGDR influences changes in lung function over time. Meta‐analysis incorporated the findings of this study with those of two previous studies in Caucasian populations.

Results:  Cross‐sectional associations between PTGDR haplotypes and asthma phenotypes were non‐significant (P > 0.05) in both populations. Longitudinal analyses of PTGDR and lung function were also non‐significant. Meta‐analysis, however, suggested that haplotype TCT was significantly associated with decreased risk of asthma (OR = 0.76; P = 0.02) while haplotype CCC was not significantly associated with asthma (OR = 1.30; P = 0.07).

Conclusions:  These results suggest that despite the non‐significant findings in the present study populations, PTGDR promoter haplotypes may account for a small but significant proportion of the risk of asthma in Caucasian populations.
Effect of early pulmonary rehabilitation on health care utilization and health status in patients hospitalized with acute exacerbations of COPD
Authors: KO FANNY W.S. , DAI DAVID L.K. , NGAI JENNY , TUNG ALVIN , NG SUSANNA , LAI KENNETH , FONG RICKY , LAU HERMAN , TAM WILSON , HUI DAVID S.C.
Published: December 2010

Background and objective:  Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) incur heavy utilization of health‐care resources for patients who require hospitalization. We evaluated whether an early outpatient pulmonary rehabilitation programme (PRP) after hospitalization for AECOPD could reduce acute health‐care utilization over the succeeding year.

Methods:  Sixty patients admitted with AECOPD were randomized to either PRP or usual care (UC). The PRP group received 8 weeks of outpatient rehabilitation programme 2–3 weeks after discharge from hospital. Lung function, 6 min walk test and dyspnoea score were assessed at baseline, 3, 6, 9 and 12 months, while St George's respiratory questionnaire and cardiopulmonary exercise test were assessed at baseline, 3, 6 and 12 months.

Results:  The PRP and UC groups demonstrated a 53.3% and 43.3% risk of readmissions at 12 months (incident risk ratio 0.97 (95% CI: 0.57–1.60), P = 0.90). The mean readmission rates were 1.00 ± 1.20 and 1.03 ± 1.87 (P = 0.47) for the PRP versus UC groups respectively. The rates of AECOPD and emergency department visits were similar between the two groups. The St George's respiratory questionnaire total score was lower in the PRP group (40.15 ± 19.10 vs 46.91 ± 18.21, P = 0.01 and 42.3 ± 20.06 vs 51.44 ± 18.98 P = 0.01 at 3 and 6 months respectively). There were no statistically significant differences in the FEV1% predicted, dyspnoea score, 6 min walk test and maximal oxygen consumption during exercise test between PRP and UC at different time points.

Conclusions:  An early rehabilitation programme following AECOPD led to improvement in quality of life up to 6 months, but did not reduce health‐care utilization at 1 year.
Cardiovascular risk modification in participants with coronary disease screened by the Kidney Early Evaluation Program
Authors: McCullough P. A. , Whaley‐Connell A. , Brown W. W. , Collins A. J. , Chen S.‐C. , Li S. , Norris K. C. , Jurkovitz C. , McFarlane S. , Obialo C. , Sowers J. , Stevens L. , Vassalotti J. A. , Bakris G. L.
Published: December 2010

Background: Coronary artery disease (CAD) identifies the need for intensive treatment of risk factors among individuals with chronic kidney disease (CKD), a high‐risk, complex cardiovascular risk state.

Methods: An estimated glomerular filtration rate <60 mL/min/1.73 m2 or a urine albumin : creatinine ratio (ACR) ≥ 30 mg/g (3.4 mg/mmol) defined CKD.

Results: Of 70 454 volunteers screened the mean age was 53.5 ± 15.7 years and 68.3% were female. A total of 5410 (7.7%) had a self‐reported history of CAD; 1295 (1.8%) had a history of prior percutaneous coronary intervention (PCI); and 1124 (1.6%) had a prior history of coronary artery bypass surgery (CABG). Multivariate analysis for the outcome of suboptimal CAD risk management (composite of systolic blood pressure ≥130 mmHg, glucose ≥125 mg/dL (6.9 mmol/L) for diabetics, total cholesterol ≥200 mg/dL (5.2 mmol/L), or current smoking; n= 38 746/53 403, 72.5%) revealed older age (per year) (odds ratio (OR) = 1.04, 95% confidence interval (CI) 1.03–1.04, P < 0.0001), male gender (OR = 1.40, 95% CI 1.34–1.47, P < 0.0001), ACR ≥ 30 mg/g (3.4 mg/mmol) (OR = 1.66, 95% CI 1.55–1.79, P < 0.0001), body mass index (per kg/m2) (OR = 1.06, 95% CI 1.06–1.06, P < 0.0001), CAD without a history of revascularization (OR = 1.14, 95% CI 1.02–1.28, P= 0.02) and care received by a nephrologist (OR = 1.49, 95% CI 1.22–1.83, P < 0.0001) were associated with worse risk factor control. Prior coronary revascularization and being under the care of a cardiologist were not associated with either improved or suboptimal risk factor control.

Conclusions: Chronic kidney disease is associated with overall poor rates of CAD risk factor control.
Hypoglycaemia‐induced myocardial infarction as a result of sulphonylurea misuse
Authors: Corley B. T. , Davenport C. , Delaney L. , Hatunic M. , Smith D.
Published: December 2010

Diabet. Med. 28, 876–879 (2011)

Background  Recent large‐scale randomized trials of intensive therapy in Type 2 diabetes have reported increased cardiovascular morbidity and mortality in patient populations who experience a high frequency of hypoglycaemic events. However, there are few descriptions of hypoglycaemia leading directly to a myocardial infarction (MI) in the medical literature to date.

Case report  In this article we describe the case of a 76‐year‐old woman without diabetes who presented with symptoms, left bundle branch block and raised troponin, indicative of an MI. She was also noted to be hypoglycaemic with a plasma glucose level of 2.5 mmol/l. It was subsequently discovered that she had mistakenly been dispensed glibenclamide, a long‐acting sulphonylurea, in the preceding weeks. Her cardiac symptoms resolved completely upon treatment of her hypoglycaemia and she had no significant coronary artery disease on angiography.

Conclusion  This is the first case of sulphonylurea‐induced MI in a patient without diabetes and illustrates the adverse effects of acute hypoglycaemia upon the cardiovascular system.
SCREENING AND MERGER ACTIVITY*
Authors: BANAL‐ESTAÑOL ALBERT , HEIDHUES PAUL , NITSCHE RAINER , SELDESLACHTS JO
Published: December 2010

In our paper, the target of a proposed merger, by setting a reserve price, is able to screen prospective acquirers according to their (expected) ability to generate merger‐specific synergies. Both empirical evidence and many merger models suggest that the difference between high and low‐synergy mergers becomes smaller during booms. Thus, a target's opportunity cost for sorting out relatively less fitting acquirers increases and, hence, targets screen less tightly during booms, which leads to a hike in merger activity. Our screening mechanism not only predicts that merger activity is intense during booms and subdued during recessions but is also consistent with other stylized facts about takeovers and generates novel testable predictions.
CARTELISING GROUPS IN DYNAMIC HYPERBOLIC OLIGOPOLY WITH ANTITRUST THRESHOLD
Authors: MATSUMOTO AKIO , MERLONE UGO , SZIDAROVSZKY FERENC
Published: December 2010

Empirical evidence, and theoretical results have shown that, in an industry, higher concentration index indicates higher price‐cost margin. In order to detect collusive behaviour the antitrust authorities often monitor the Herfindahl‐Hirschman Index. We consider N‐firm oligopolies where a group of firms partially cooperate with each other, and monitor the Herfindahl‐Hirschman Index as well. After suspecting that the authorities might notice the violation of antitrust regulations, they stop their cooperation. The group will not cooperate again until the Index moves back to the legal domain. This flip‐flop dynamical model is formulated, the equilibria are determined, and the asymptotic properties of the system are examined.
A Political Economy Model of Merger Policy in International Markets
Authors: MOTTA MASSIMO , RUTA MICHELE
Published: December 2010

This paper looks at the political economy of merger policy under autarky and in international markets. We assume that merger policy is decided by antitrust authorities—whose objective is to maximize welfare—but can be influenced by governments, which are subject to lobbying by firms (insiders or outsiders to the merger). We argue that political economy distortions may explain some of the recently observed merger policy conflicts between authorities and politicians, as well as between institutions belonging to different countries. We illustrate our analysis with applications motivated by recent merger cases that have been widely debated in the international press.
Impact of species variability and ‘probe‐dependence’ on the detection andin vivovalidation of allosteric modulation at the M4muscarinic acetylcholine receptor
Authors: Suratman S , Leach K , Sexton PM , Felder CC , Loiacono RE , Christopoulos A
Published: December 2010

BACKGROUND AND PURPOSEWe recently characterized LY2033298 as a novel allosteric modulator and agonist at M4muscarinic acetylcholine receptors (mAChRs). Evidence also suggested a difference in the potency of LY2033298 at rodent relative to human M4mAChRs. The current study investigated the basis for the species difference of this modulator and used this knowledge to rationalize itsin vivoactions.

EXPERIMENTAL APPROACHLY2033298 was investigatedin vitroin CHO cells stably expressing human or mouse M4mAChRs, using assays of agonist‐induced ERK1/2 or GSK‐3α phosphorylation, [35S]‐GTPγS binding, or effects on equilibrium binding of [3H]‐NMS and ACh. Thein vivoactions of LY2033298 were investigated in a mouse model of amphetamine‐induced locomotor activity. The function of LY2033298 was examined in combination with ACh, oxotremorine or xanomeline.

KEY RESULTSLY2033298 had similar affinities for the human and mouse M4mAChRs. However, LY2033298 had a lower positive co‐operativity with ACh at the mouse relative to the human M4mAChR. At the mouse M4mAChR, LY2033298 showed higher co‐operativity with oxotremorine than with ACh or xanomeline. The different degrees of co‐operativity between LY2033298 and each agonist at the mouse relative to the human M4mAChR necessitated the co‐administration of LY2033298 with oxotremorine in order to showin vivoefficacy of LY2033298.

CONCLUSIONS AND IMPLICATIONSThese results provide evidence for species variability when comparing the allosteric interaction between LY2033298 and ACh at the M4mAChR, and also highlight how the interaction between LY2033298 and different orthosteric ligands is subject to ‘probe dependence’. This has implications for the validation of allosteric modulator actionsin vivo.
γ‐Tocotrienol is a novel inhibitor of constitutive and inducible STAT3 signalling pathway in human hepatocellular carcinoma: potential role as an antiproliferative, pro‐apoptotic and chemosensitizing agent
Authors: Rajendran Peramaiyan , Li Feng , Manu Kanjoormana Aryan , Shanmugam Muthu K. , Loo Ser Yue , Kumar Alan Prem , Sethi Gautam
Published: December 2010

BACKGROUND AND PURPOSE

Activation of signal transducer and activator of transcription 3 (STAT3) play a critical role in the survival, proliferation, angiogenesis and chemoresistance of tumour cells. Thus, agents that suppress STAT3 phosphorylation have potential as cancer therapies. In the present study, we investigated whether the apoptotic, antiproliferative and chemosensitizing effects of γ‐tocotrienol are associated with its ability to suppress STAT3 activation in hepatocellular carcinoma (HCC).

EXPERIMENTAL APPROACH

The effect of γ‐tocotrienol on STAT3 activation, associated protein kinases and phosphatase, STAT3‐regulated gene products, cellular proliferation and apoptosis in HCC cells was investigated.

KEY RESULTS

γ‐Tocotrienol inhibited both the constitutive and inducible activation of STAT3 with minimum effect on STAT5. γ‐Tocotrienol also inhibited the activation of Src, JAK1 and JAK2 implicated in STAT3 activation. Pervanadate reversed the γ‐tocotrienol‐induced down‐regulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that γ‐tocotrienol induced the expression of the tyrosine phosphatase SHP‐1 and deletion of the SHP‐1 gene by small interfering RNA abolished the ability of γ‐tocotrienol to inhibit STAT3 activation. γ‐Tocotrienol also down‐regulated the expression of STAT3‐regulated gene products, including cyclin D1, Bcl‐2, Bcl‐xL, survivin, Mcl‐1 and vascular endothelial growth factor. Finally, γ‐tocotrienol inhibited proliferation, induced apoptosis and significantly potentiated the apoptotic effects of chemotherapeutic drugs (paclitaxel and doxorubicin) used for the treatment of HCC.

CONCLUSIONS AND IMPLICATIONS

Overall, these results suggest that γ‐tocotrienol is a novel blocker of the STAT3 activation pathway, with a potential role in future therapies for HCC and other cancers.
Glucocorticosteroids: current and future directions
Authors: Barnes Peter J
Published: December 2010

Glucocorticoids are the most effective anti‐inflammatory therapy for asthma yet are relatively ineffective in chronic obstructive pulmonary disease. Glucocorticoids suppress inflammation via several molecular mechanisms. Glucocorticoids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, by reversing histone acetylation of activated inflammatory genes through binding of ligand‐bound glucocorticoid receptors (GR) to co‐activator molecules and recruitment of histone deacetylase‐2 to the activated inflammatory gene transcription complex (trans‐repression). At higher concentrations of glucocorticoids GR homodimers interact with DNA recognition sites to activate transcription through increased histone acetylation of anti‐inflammatory genes and transcription of several genes linked to glucocorticoid side effects (trans‐activation). Glucocorticoids also have post‐transcriptional effects and decrease stability of some pro‐inflammatory mRNA species. Decreased glucocorticoid responsiveness is found in patients with severe asthma and asthmatics who smoke, as well as in all patients with chronic obstructive pulmonary disease. Several molecular mechanisms of glucocorticoid resistance have now been identified which involve post‐translational modifications of GR. Histone deacetylase‐2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti‐inflammatory actions of glucocorticoids. Dissociated glucocorticoids and selective GR modulators which show improved trans‐repression over trans‐activation effects have been developed to reduce side effects, but so far it has been difficult to dissociate anti‐inflammatory effects from adverse effects. In patients with glucocorticoid resistance alternative anti‐inflammatory treatments are being investigated as well as drugs that may reverse the molecular mechanisms of glucocorticoid resistance.

LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐1
Go Down to Suffering and Raise it Up
Authors: Abrams Sarah E.
Published: December 2010

ABSTRACT
In a partial reprint of a January 1919 editorial from The Public Health Nurse, readers will find an Editor's attempt to find meaning in the long, bitter, and highly destructive Great War, known in contemporarily as World War I. The Editor expresses hope that something constructive can emerge from so much devastation. Parallels to contemporary conflicts are readily apparent. Veterans, specifically nurses returning from the battlefields of Europe in this excerpt, deserve acknowledgement and through the knowledge of suffering gained in war, use the skills they possess to advance health and human happiness in times of peace.
Heat shock protein 47 expression in oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells
Authors: Lee Shiuan‐Shinn , Tseng Ling‐Hsien , Li Yi‐Ching , Tsai Chung‐Hung , Chang Yu‐Chao
Published: December 2010

J Oral Pathol Med (2010) 40: 390–396

Background:  Heat shock protein 47 (HSP47) is a product of CBP2 gene located at chromosome 11q13.5, a region frequently amplified in human cancers. Areca quid chewing is a major risk factor of oral squamous cell carcinoma (OSCC). The aim of this study was to compare HSP47 expression in normal human oral epithelium and OSCC and further to explore the potential mechanisms that may lead to induce HSP47 expression.

Methods:  Thirty‐two OSCC specimens and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line OC2 cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N‐acetyl‐l‐cysteine (NAC), extracellular signal‐regulated protein kinase (ERK) inhibitor PD98059, phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002, cyclooxygenase‐2 inhibitor NS‐398, and tyrosine kinase inhibitor herbimycin A were added to find the possible regulatory mechanisms.

Results:  HSP47 expression was significantly higher in OSCC specimens than normal epithelium (P < 0.05). No significant difference in HSP47 expression was observed with respect to age, sex, T category, stage, and differentiation (P > 0.05). The lower HSP47 expression was associated with lymph node metastasis (P = 0.015). Arecoline was found to elevate HSP47 expression in a dose‐ and time‐dependent manner (P < 0.05). The addition of NAC, PD98059, LY294002, NS398, and herbimycin A markedly inhibited the arecoline‐induced HSP47 expression (P < 0.05).

Conclusion:  Our findings demonstrated that HSP47 expression is significantly upregulated in areca quid chewing‐associated OSCCs. HSP47 could be used clinically as a marker for lymph node metastasis of oral carcinogenesis. In addition, arecoline‐induced HSP47 expression was downregulated by NAC, PD98059, LY294002, NS398, and herbimycin A.
Glucose oxidase prevents programmed cell death of the silkworm anterior silk gland through hydrogen peroxide production
Authors: Matsui Hiroto , Kakei Motonori , Iwami Masafumi , Sakurai Sho
Published: December 2010

During pupal metamorphosis, the anterior silk glands (ASGs) of the silkworm Bombyx mori degenerate through programmed cell death (PCD), which is triggered by 20‐hydroxyecdysone (20E). 20E triggers the PCD of the ASGs of day 7 fifth instar (V7) larvae but not that of V5 larvae. When V7 ASGs were cocultured with V5 ASGs in the presence of 20E, neither culture of ASGs underwent PCD. The 20E‐induced PCD of V7 ASGs was also inhibited when they were incubated in conditioned medium that was prepared by incubating V5 ASGs for 48 h, an indication that V5 ASGs released an inhibitor of 20E‐induced PCD during incubation. The inhibitor was purified from conditioned medium and identified as glucose oxidase (GOD). GOD catalyzes the oxidation of glucose to gluconolactone, and generates hydrogen peroxide as a byproduct. We found that hydrogen peroxide is the molecule that directly inhibits the action of 20E and may act to protect the ASGs from early execution of PCD during the feeding stage. GOD was localized in the inner cavity of the gland, and was discharged to the outside of the ASGs with the silk thread at the onset of spinning. Thus, the spinning behavior, occurring at the beginning of the prepupal period, plays an important role in controlling the time at which ASGs undergo PCD in response to 20E.
Mini-radio lobes in AGN core illumination and their hadronic gamma-ray afterlight
Authors: Kino Motoki , Asano Katsuaki
Published: December 2010

Recent radio observations reveal the existence of mini-radio lobes in active galaxies with scales of ∼10 pc. The lobes are expected to be filled with shock-accelerated electrons and protons. In this work, we examine the photon spectra from the mini-lobes, properly taking the hadronic processes into account. We find that the resultant broad-band spectra contain the two distinct hadronic bumps in γ-ray bands, i.e. the proton synchrotron bump at ∼1 MeV and the synchrotron bump at ∼1 GeV due to the secondary electrons/positrons produced via photo-pion cascade. In particular, when the duration of particle injection is shorter than the lobe age, radio-dark γ-ray lobes are predicted. The existence of the γ-ray lobes could be testable with the future TeV–γ Cherenkov Telescope Array.
Phase Chemistry Study of the Zabuye Salt Lake Brine: Isothermal Evaporation at 15°C and 25°C
Authors: Zhen NIE , Lingzhong BU , Mianping ZHENG , Yongsheng ZHANG
Published: December 2010

Zabuye Salt Lake in Tibet, China is a carbonate‐type salt lake, which has some unique characteristics that make it different from other types of salt lakes. The lake is at the latter period in its evolution and contains liquid and solid resources. Its brine is rich in Li, B, K and other useful minor elements that are of great economic value. We studied the concentration behavior of these elements and the crystallization paths of salts during isothermal evaporation of brine at 15°C and 25°C. The crystallization sequence of the primary salts from the brine at 25°C is halite (NaCl) → aphthitalite (3K2SO4·Na2SO4) → zabuyelite (Li2CO3) → trona (Na2CO3·NaHCO3·2H2O) → thermonatrite (Na2CO3·H2O) · sylvite (KCl), while the sequence is halite (NaCl) → sylvite (KCl) → trona (Na2CO3·NaHCO3·2H2O) → zabuyelite (Li2CO3) → thermonatrite (Na2CO3·H2O) → aphthitalite (3K2SO4·Na2SO4) at 15°C. They are in accordance with the metastable phase diagram of the Na+, K+‐Cl−, CO32−, SO42−‐H2O quinary system at 25°C, except for Na2CO3·7H2O which is replaced by trona and thermonatrite. In the 25°C experiment, zabuyelite (Li2CO3) was precipitated in the early stage because Li2CO3 is supersaturated in the brine at 25°C, in contrast with that at 15°C, it precipitated in the later stage. Potash was precipitated in the middle and late stages in both experiments, while boron was concentrated in the early and middle stages and precipitated in the late stage.
Discovery of Mass Independent Oxygen Isotopic Compositions in Superscale Nitrate Mineral Deposits from Turpan‐Hami Basin, Xinjiang, China and Its Significance
Authors: Yanhe LI , Yan QIN , Feng LIU , Kejun HOU , Defang WAN
Published: December 2010

The Turpan‐Hami Basin in eastern Xinjiang is one of the driest regions on Earth and a premier environment to form and preserve nitrate. A large nitrate ore field in this basin was found recently. It is estimated there are about 2.5 billion tons of resources of nitrate, and the amount is as much as the Atacama Desert super‐scale nitrate deposit in Chile. Nitrate is one of a few minerals with mass‐independent fractionation (MIF), and the oxygen isotope MIF is an effective method to determine the source of nitrate. The δ17O, δ18O of nitrate were measured by fluorination and thermal decomposition method. The date indicated that this is the first time that oxygen isotope MIF has been located in inland nitrate minerals. The results obtained by two methods are similar, Δ17O=δ17O–0.52×δ18O=12‰–17‰. The experiment and observation data proved that oxygen isotope MIF of nitrate are the result of photochemical reactions in the troposphere and stratosphere. Thus, evidence from MIF oxygen isotopic compositions indicate that long term atmospheric deposition of nitrate aerosol particles produced by photochemical reactions is the source of the deposits.
Rapid Identification and Emergency Investigation of Surface Ruptures and Geohazards Induced by the Ms 7.1 Yushu Earthquake
Authors: Yongshuang ZHANG , Xin YAO , Tanyu XIONG , Yinsheng MA , Daogong HU , Nong YANG , Changbao GUO
Published: December 2010

The rapid identification based on InSAR technology was proved to be effective in our emergency investigation of surface ruptures and geohazards induced by the Yushu earthquake. The earthquake‐generating fault of the Yushu earthquake is the Yushu section of the Garzê‐Yushu faults zone. It strikes NWW‐NW, 23 km long near the Yushu County seat, dominated by left‐lateral strike slip, and appearing as a surface rupture zone. The macroscopic epicenter is positioned at Guo‐yang‐yan‐song‐duo of Gyegu Town (33°03′11″N, 96°51′26″E), where the co‐seismic horizontal offset measured is 1.75 m. Geohazards induced by the Yushu earthquake are mainly rockfalls, landslides, debris flows, and unstable slopes. They are controlled by the earthquake‐generating fault and are mostly distributed along it. There are several geohazard chains having been established, such as earthquake, canal damage, soil liquefying, landslide‐debris flow, earthquake, soil liquefying, roadbed deformation, etc. In order to prevent seismic hazards, generally, where there is a visible surface rupture induced by the Yushu earthquake, reconstruction should be at least beyond 20 m, on each side, from it. Sufficient attention should also be given to potential geohazards or geohazard chains induced by the earthquake.
Sediment‐hosted Pb‐Zn Deposits in Southwest Sanjiang Tethys and Kangdian Area on the Western Margin of Yangtze Craton
Authors: Changming WANG , Jun DENG , Shouting ZHANG , Chunji XUE , Liqiang YANG , Qingfei WANG , Xiang SUN
Published: December 2010

The western margin of Yangtze Craton is known as a significant sediment‐hosted base‐metal aggregate cluster, especially for Pb–Zn deposits in China, e.g. Jinding, Daliangzi, Tianbaoshan, Kuangshanchang and Qinlinchang deposits. In comparison with the classic MVT deposits in the world, based on the basic geology of the sediment‐hosted Pb‐Zn deposits, this paper focuses on temporalspatial distribution of this deposit to further discuss its large scale mineralization and tectonic evolution history. In the SW Sanjiang Thethys, Jinding deposit is typically thrust fault‐controlled and hosted mainly in the sandstones and breccia‐bearing sandstones, whereas MVT‐type deposits are controlled by lithology and faulting/fracturing with a strong preference for carbonate‐hosted rocks. Most importantly, Jinding Pb–Zn deposit differs from the other types of sediment‐hosted Pb–Zn deposits in which it was formed in a strongly deformed foreland basin within a continental collision zone. In the Kangdian area, the sediment‐hosted Pb–Zn deposits were formed in the extensional basin on the side of the continental orogenic belt along the Yangtze Craton. Compared with classic MVT deposits, the Pb–Zn deposits in the Kangdian area belong to MVT deposits. This paper is significant not only for interpretation of the genesis of sediment‐hosted Pb–Zn deposits but also for exploiting large base metal deposits in large sedimentary target areas.
Pool‐Forming Stages and Enrichment Models of Medium‐ to High‐Rank Coalbed Methane
Authors: Yan SONG , Mengjun ZHAO , Feng HONG , Shaobo LIU , Shengfei QIN , Hongyan WANG
Published: December 2010

The pool‐forming mechanism of coalbed methane has its own characteristics. In this paper, based on studies on the typical coal‐bearing basins in China, it is pointed out that the reservoir formation of medium‐ to high‐rank coalbed methane has experienced three critical stages: the coalbed methane generation and adsorption stage, the coalbed adsorption capacity enhancement stage, and the coalbed methane desorption‐diffusion and preservation stage. The regional tectonic evolution, hydrodynamic conditions and sealing conditions play important roles in the stage of coalbed methane desorption‐diffusion and preservation. Medium‐ to high‐rank coalbed methane has three types of enrichment models, that is, the most favorable, the relatively favorable, and the unfavorable enrichment models.