bluuebunny/crossref_metadata_2025 huggingface dataset:
An Extension of the Regression of Offspring on Mid‐Parent to Test for Association and Estimate Locus‐Specific Heritability: The Revised ROMP Method
Authors: Roy‐Gagnon M.‐H. , Mathias R. A. , Fallin M. D. , Jee S. H. , Broman K. W. , Wilson A. F.
Published: December 2007

The Regression of Offspring on Mid‐Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMPrev) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus‐specific heritability estimate. The ROMPrev test had good power at the 5% significance level with properly controlled type I error. Locus‐specific heritability estimates were, on average, close to simulated values. For non‐zero locus‐specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest.

ROMPrev was applied to a study of cardiovascular‐related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMPrev method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus‐specific heritability while minimizing the genotyping required.
Micro‐magnetic resonance imaging of avian embryos
Authors: Li Xiaojing , Liu Jia , Davey Megan , Duce Suzanne , Jaberi Neema , Liu Gang , Davidson Gemma , Tenent Seaneen , Mahood Ruth , Brown Phoebe , Cunningham Craig , Bain Andrew , Beattie Kevin , McDonald Laura , Schmidt Katy , Towers Matthew , Tickle Cheryll , Chudek Sandy
Published: December 2007

Chick embryos are useful models for probing developmental mechanisms including those involved in organogenesis. In addition to classic embryological manipulations, it is possible to test the function of molecules and genes while the embryo remains within the egg. Here we define conditions for imaging chick embryo anatomy and for visualising living quail embryos. We focus on the developing limb and describe how different tissues can be imaged using micro‐magnetic resonance imaging and this information then synthesised, using a three‐dimensional visualisation package, into detailed anatomy. We illustrate the potential for micro‐magnetic resonance imaging to analyse phenotypic changes following chick limb manipulation. The work with the living quail embryos lays the foundations for using micro‐magnetic resonance imaging as an experimental tool to follow the consequences of such manipulations over time.
Sexual segregation in Tibetan gazelle: a test of the activity budget hypothesis
Authors: Li Z. , Jiang Z.
Published: December 2007

Tibetan gazelle Procapra picticaudata, a threatened endemic species on the Qinghai‐Tibet Plateau, is a sexually dimorphic ungulate. Males are larger than females and both sexes live in different groups, except during the rutting season. In order to test the activity budget hypothesis, which was proposed to explain social segregation in ungulates, we studied the activity budget of male and female Tibetan gazelles during the summers of 2005 and 2006. The activity budget hypothesis predicts that females spend more time feeding and group members synchronize their activities more in the same‐sex groups than in the mixed‐sex groups. We found that females and males of Tibetan gazelle had different activity budgets; females spent significantly longer time feeding and comparably less time on other activities. Activity synchronization indexes between female groups and male groups were similar (female groups: 0.81±0.17, male groups: 0.80±0.19), whereas both of them were significantly higher than that of mixed‐sex groups (0.58±0.29). These results suggest that although sexual segregation might be caused by multiple mechanisms, the activity budget hypothesis about sexual segregation is supported by our studies of Tibetan gazelle on the Qinghai‐Tibet Plateau.
Cranial mechanics compared in extinct marsupial and extant African lions using a finite‐element approach
Authors: Wroe S.
Published: December 2007

Few species have generated more or longer running controversy than Australia's extinct marsupial lion Thylacoleo carnifex (Owen, 1859). Over the last century and a half, feeding behaviours as disparate as osteophagy and specialized herbivory have been suggested and T. carnifex has been placed in both phalangeriform and vombatiform clades. Phylogenetic placement remains uncertain, but broad consensus has been achieved regarding diet, with all recent authors agreeing that T. carnifex was a carnivore. However, the marsupial lion's extraordinary cranial and dental morphologies remain without clear analogy, leaving many questions unanswered regarding how this most atypical mammalian predator killed its prey. Here I apply a rapidly emerging new approach in comparative biology, finite‐element analysis, to the examination of cranial mechanics in T. carnifex. Comparisons are made with an extant lion Panthera leo (Linnaeus, 1758) under simulations designed to model stress distributions imposed by biting (intrinsic loads) and interaction with struggling prey (extrinsic loads). Modelling that approximates the 3‐D architecture of jaw adductors suggests that both the placental and marsupial lions could generate considerably greater bite forces than has been predicted using 2‐D approaches, but with relatively greater forces in the marsupial. The distribution of cranial stress is in many respects similar in both species, but results from simulations of extrinsic forces suggest that the marsupial was particularly well adapted to resist the high stresses that would be expected in dealings with relatively large prey. On the other hand, relatively high stress recorded in the rostrum of T. carnifex under intrinsic loadings suggests that it may have deployed a very different modus operandi, wherein the carnassial teeth played an active role in effecting a kill.
Usefulness of Tricuspid Annular Velocity in Identifying Global RV Dysfunction in Patients with Primary Pulmonary Hypertension: A Comparison with 3D Echo‐Derived Right Ventricular Ejection Fraction
Authors: De Castro Stefano , Cavarretta Elena , Milan Alberto , Caselli Stefano , Di Angelantonio Emanuele , Vizza Carmine Dario , Lucchetti Diego , Patel Ayan , Kuvin Jeffrey , Pandian Natesa G.
Published: December 2007

While right ventricular (RV) function and size are important clinical markers in several cardiac conditions, the assessment of RV function by two‐dimensional (2D) echocardiography remains challenging, due to the complexity of RV geometry. We therefore sought to compare an easily‐measured parameter, peak systolic velocity of tricuspid annulus (TAPSV) obtained by tissue Doppler imaging (TDI), to right ventricular ejection fraction (RVEF) measured by real time three‐dimensional echocardiography (RT3DE) and to explore what TAPSV cutoff values would be useful in detecting global RV dysfunction. We enrolled 20 patients affected by primary pulmonary hypertension and 30 consecutive healthy volunteers, who underwent transthoracic echocardiography, RT3DE and tissue Doppler evaluation. TAPSV had a statistically significant correlation with RVEF (r = 0.66, P < 0.001). With RV dysfunction defined as RVEF <40%, a TAPSV cutoff value of 9.5 cm/sec yielded the best compromise between sensitivity, specificity, and positive predictive value and negative predictive value. In conclusion, a TAPSV cutoff value of 9.5 cm/sec yields significantly high sensitivity and specificity and appears to be a valid compromise in detecting RV dysfunction, TAPSV values however are not useful in evaluating the severity of RV dysfunction.
Chromatin‐modifying proteins in cancer
Authors: FOG CATHRINE K. , JENSEN KLAUS T. , LUND ANDERS H.
Published: December 2007

Chromatin‐modifying proteins mold the genome into areas that are accessible for transcriptional activity and areas that are transcriptionally silent. This epigenetic gene regulation allows for different transcriptional programs to be conducted in different cell types at different timepoints–despite the fact that all cells in the organism contain the same genetic information. A large amount of data gathered over the last decades has demonstrated that deregulation of chromatin‐modifying proteins is etiologically involved in the development and progression of cancer. Here we discuss how epigenetic alterations influence cancer development and review known cancer‐associated alterations in chromatin‐modifying proteins.
Clinical Manifestations of Cutaneous Lupus Erythematosus
Authors: Kuhn Annegret , Sticherling Michael , Bonsmann Gisela
Published: December 2007

Cutaneous lupus erythematosus (CLE) is a chronic inflammatory autoimmune disease with a broad spectrum of clinical manifestations and a variable course. In numerous investigations, it has been shown that exogenous factors, such as UV‐light and drugs, can induce this disease. However, not all clinical aspects can be explained and therefore, the pathogenesis of CLE is currently under extensive research. The various cutaneous manifestations of LE are divided into LE‐nonspecific and LE‐specific skin disease based on histologic criteria. LE‐nonspecific manifestations are mostly associated with systemic LE but can also occur in other diseases and include particularly vascular skin lesions such as pe‐riungual telangiectases. LE‐specific skin disease includes the subtypes of CLE such as acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), chronic cutaneous LE (CCLE), and intermittent CLE (ICLE). The subdivision of these subtypes with different prognosis and course is supported by genetic, clinical, histologic, and immunoserologic findings. The subtypes of CLE require a specific morphological and clinical analysis, which is described in the first part of this review. In the second part of this review, further diagnostic procedures and therapeutic strategies in patients with CLE are discussed.
Outcome survey of insect venom allergic patients with venom immunotherapy in a rural population
Authors: Roesch Alexander , Boerzsoenyi Julia , Babilas Philipp , Landthaler Michael , Szeimies Rolf‐Markus
Published: December 2007

Background: Hymenoptera venom anaphylaxis is a frightening event that affects physical and psychical functioning.

Patients and Methods: Retrospective survey of 182 Hymenoptera venom allergic patients living in a rural area using a questionnaire targeting on patients' satisfaction during therapy, fear of anaphylactic recurrences and changes in lifestyle before and after venom immunotherapy (VIT). Additionally, patients' self‐assessment of quality of life, daily outdoor time and re‐sting rate were recorded.

Results: 146 patients returned the questionnaire (58.9% male, 41.1% female, 25.3% honey bee allergic, 67.8% wasp allergic, 41.1% re‐sting rate, mean follow‐up time 6.5 years).Measurement of the parameters fear,satisfaction and changes in lifestyle revealed a significant improvement after VIT.This correlated with the patients'self‐assessment of quality of life,when 89.7% declared an improvement after VIT.Although the improvement was higher in patients with re‐stings, also patients without re‐stings clearly benefited from VIT. Interestingly,females were significantly more affected by Hymenoptera venom allergy than males,whereas both genders showed a similar improvement after VIT.

Conclusions: Patients with Hymenoptera venom sting allergy significantly benefit from VIT in regard to both biological and psychological outcome. VIT should still be provided to all Hymenoptera venom allergic patients as standard of care.
Female Sexual Function after Surgery for Stress Urinary Incontinence: Transobturator Suburethral Tape vs. Tension-Free Vaginal Tape Obturator
Authors: Elzevier Henk Willem , Putter Hein , Delaere Karl P.J. , Venema Pieter L. , à Nijeholt A.A.B. Lycklama , Pelger Rob C.M.
Published: December 2007

Introduction

The transobturator suburethral tape (TOT) and tension-free vaginal tape obturator (TVT-O) procedures are relatively new incontinence treatment procedures. Studies on the influence on sexual function as a result of these procedures are limited.

Aim

The influence of TOT or TVT-O for the surgical treatment of stress urinary incontinence (SUI) on female sexual function.

Methods

We evaluated 77 sexually active patients after TVT-O (N=34, mean age 53.2 years) and TOT (OB-TAPE, Porges) (N=44, mean age 52.0 years) placement for SUI based on the responses to a mailed questionnaire 3 months after the operation.

Main Outcome Measure

Difference in postoperative sexual complaints related to the TVT-O (inside-out) and TOT (outside-in) procedure.

Results

Postoperative TOT and TVT-O: There was almost no difference in frequency of sexual intercourse and an improvement of the continence during intercourse; continence was reported in 33 patients (42.3%) before and 67 patients (78.4%) after operation. The appreciation of sexual intercourse was improved in 15 patients (19.2%) and worsened in eight patients (10.3%). Postoperative TVT-O vs. TOT: No difference was seen in lost of lubrication, clitoral tumescence reduction, and clitoral sensibility reduction between both procedures. Pain because of vaginal narrowing was seen significantly more in the TOT procedure group.

Conclusion

Overall, in this study, the technique of TOT gave rise to more sexual dysfunction than TVT-O. However, because of the successful outcome on incontinence, both procedures had, overall, a positive effect on sexual function. The cause of significant more pain during intercourse as a result of vaginal narrowing in the TOT procedure requires further investigation. Like other studies, this study demonstrated that incontinence surgery can have a positive and negative outcome on sexual function. It is important to put this issue in the informed consent.
Urologist Practice Patterns in the Management of Peyronie's Disease: A Nationwide Survey
Authors: Shindel Alan W. , Bullock Travis L. , Brandes Steven
Published: December 2007

Introduction

Peyronie's disease (PD) is a poorly understood clinical entity.

Aim

We endeavored to determine how contemporary urologists in the United States manage PD.

Methods

A randomly generated mailing list of 996 practicing urologists was generated from the American Urologic Association member directory. A specifically designed survey was mailed with a cover letter and a postage-paid return envelope.

Main Outcome Measure

Our survey assessed several practice-related factors and asked questions of how the subject would manage various presentations of PD in their practice. Four cases were presented: case 1, a healthy 55-year-old man with painless 30° dorsal curvature of 16 months duration; case 2, a 60-year-old man with 35° dorsal curvature, 4/10 pain on visual analog scale, of 6 months duration; case 3, a 62-year-old man with painless 60° dorsal curvature and erectile dysfunction responsive to alprostadil suppository of 2 years duration; and case 4, a 50-year-old man with mid-shaft waist deformity, foreshortening, no pain/curvature/erectile dysfunction.

Results

Responses were received from 236 (24%) practicing urologists. Vitamin E was the preferred initial management for 70% of respondents, with observation, Potaba (Glenwood, Englewood, New Jersey, USA), colchicine, verapamil injections, and verapamil gel favored by 32, 20, 12, 7, and 10% of respondents, respectively. Fifty-seven percent of respondents performed surgery for PD, with penile prostheses, Nesbit procedure, grafting, and plication used by 76, 66, 55, and 51% of respondents, respectively. Medical therapy and/or observation was the preferred management for all of the cases except case 3, for which penile prosthesis placement and referral were the favored options by 39 and 30% of urologists, respectively.

Conclusions

Medical therapy is the initial treatment for PD among American urologists. Penile prosthesis is the treatment of choice in impotent patients. Most American urologists conform to recommended practice patterns in the management of PD.
HLA‐DPβ chain may confer the susceptibility to hepatitis C virus‐associated hypertrophic cardiomyopathy
Authors: Shichi D. , Matsumori A. , Naruse T. K. , Inoko H. , Kimura A.
Published: December 2007

Hypertrophic cardiomyopathy (HCM) is a heart muscle disease characterized by hypertrophy and diastolic dysfunction of cardiac ventricles. It is suggested that one possible aetiology of HCM is the hepatitis C virus (HCV) infection, but molecular mechanisms underlying development of HCV‐associated HCM (HCV‐HCM) remains unknown. Because the human leucocyte antigen (HLA) molecule is involved in the control of progression/suppression of viral infection, extensive HLA allelic diversity may modulate the post‐infectious course of HCV and pathogenesis of HCV‐HCM. Here we undertook a case‐control study with 38 patients with HCV‐HCM and 132 unrelated healthy controls to reveal the potential impact of polymorphisms in seven classical and two non‐classical HLA genes on the pathogenesis of HCV‐HCM. It was found that DPB1*0401 and DPB1*0901 were significantly associated with increased risk to HCV‐HCM in dominant model (P < 0.028, OR = 3.94, 95% confidence interval (CI) = 1.19, 13.02) and in recessive model (P < 0.007, OR = 9.85, 95% CI = 1.83, 53.04), respectively. The disparity in the gene–dose effect by two susceptible DPB1 alleles may be attributable to the difference between the susceptible (36 A and 55 A) and resistant (8L, 9F, 11G, 57E and 76M) residue‐combination consisting of DPβ anchor pocket for antigenic peptide‐binding. These results implied that the HLA‐DP molecules with specificity pocket appropriate for HCV antigen(s) might confer the progressive process of HCM among the HCV‐infected individuals.
Salmonellaand on‐farm risk factors in healthy slaughter‐age cattle and sheep in eastern Australia
Authors: Vanselow BA , Hornitzky MA , Walker KH , Eamens GJ , Bailey GD , Gill PA , Coates K , Corney B , Cronin JP , Renilson S
Published: December 2007

Objective  To examine healthy slaughter‐age cattle and sheep on‐farm for the excretion ofSalmonellaserovars in faeces and to identify possible risk factors using a questionnaire.

Procedure  The study involved 215 herds and flocks in the four eastern states of Australia, 56 with prior history of salmonellosis. Production systems examined included pasture beef cattle, feedlot beef cattle, dairy cattle, prime lambs and mutton sheep and animals were all at slaughter age. From each herd or flock, 25 animals were sampled and the samples pooled forSalmonellaculture. AllSalmonellaisolated were serotyped and anySalmonellaTyphimurium isolates were phage typed. Questionnaires on each production system, prepared in Epi Info 6.04, were designed to identify risk factors associated withSalmonellaspp excretion, with separate questionnaires designed for each production system.

Results  Salmonellaewere identified in all production systems and were more commonly isolated from dairies and beef feedlots than other systems. Statistical analysis revealed that dairy cattle were significantly more likely to shedSalmonellain faeces than pasture beef cattle, mutton sheep and prime lambs (P < 0.05). A wide diversity ofSalmonellaserovars, all of which have been isolated from humans in Australia, was identified in both cattle and sheep. Analysis of the questionnaires showed access to new arrivals was a significant risk factor forSalmonellaexcretion on dairy properties. For beef feedlots, the presence of large numbers of flies in the feedlot pens or around stored manure were significant risk factors forSalmonellaexcretion.

Conclusion  Dairy cattle pose the highest risk of all the slaughter‐age animals tested. Some of the identified risk factors can be overcome by improved management practices, especially in relation to hygiene.
An interview with Thomas Schelling
Authors: Carvalho Jean‐Paul
Published: December 2007

Jean‐Paul Carvalhol interviewed Thomas Schelling, winner of the 2005 Nobel Memorial Prize in Economics, for Oxonomics. The interview took place at Professor Schelling's house in Maryland on 14 May 2007.
Intelligence failures: a political economy perspective
Authors: Patacconi Andrea
Published: December 2007

In this article I discuss recent episodes of military intelligence failures. Many believe that in the case of Iraq intelligence community judgements were warped by inappropriate political pressure to build a case for war. I examine that claim in a simple framework where disclosure of information gives policymakers an incentive to ‘fix the evidence’ around their preferred policy. The analysis suggests that making government more transparent creates a trade‐off between manipulation of information and accountability. The most surprising finding is that insulating intelligence agencies from political pressure may sometimes reduce voter welfare.
Modelling a century and a half of UK macroeconomic data using general to specific methodology
Authors: Castle Jennifer L.
Published: December 2007

Growth, structural change and evolution is endemic in any economy, and yet we require well‐specified, constant parameter econometric models of macro phenomena to understand economies, forecast and undertake policy analysis. This article draws on recent developments in econometric modelling, including general‐to‐specific modelling, non‐linearity testing and modelling, and outlier detection using indicator saturation, to propose a methodology in which constant parameter models can be built over long periods, yielding substantial insights into macroeconomic behaviour over a century and a half.
Telithromycin Resistance in
Streptococcus pneumoniae
Is Conferred by a Deletion in the Leader Sequence of
erm
(B) That Increases rRNA Methylation
Authors: Wolter Nicole , Smith Anthony M. , Farrell David J. , Northwood John Blackman , Douthwaite Stephen , Klugman Keith P.
Published: December 2007

A telithromycin-resistant clinical isolate of
Streptococcus pneumoniae
(strain P1501016) has been found to contain a version of
erm
(B) that is altered by a 136-bp deletion in the leader sequence. By allele replacement mutagenesis, a second strain of
S. pneumoniae
(PC13) with a wild-type
erm
(B) gene was transformed to the telithromycin-resistant phenotype by introduction of the mutant
erm
(B) gene. Whereas the wild-type PC13 strain showed slight telithromycin resistance only after induction by erythromycin (telithromycin MIC increased from 0.06 to 0.5 μg/ml), the transformed PC13 strain is constitutively resistant (MIC of 16 μg/ml). Expression of
erm
(B) was quantified by real-time reverse transcription-PCR in the presence of erythromycin or telithromycin;
erm
(B) expression was significantly higher in the transformed PC13 strain than the wild-type strain. Furthermore, the transformed strain had significantly higher levels of ribosomal methylation in the absence as well as in the presence of the antibiotics. Growth studies showed that the transformed PC13 strain had a shorter lag phase than the wild-type strain in the presence of erythromycin. Telithromycin resistance is conclusively shown to be conferred by the mutant
erm
(B) gene that is expressed at a constitutively higher level than the inducible wild-type gene. Elevated
erm
(B) expression results in a higher level of rRNA methylation that presumably hinders telithromycin binding to the ribosome.
In Vitro Activities of Voriconazole, Itraconazole, and Terbinafine Alone or in Combination against
Pythium insidiosum
Isolates from Brazil
Authors: Argenta Juliana S. , Santurio Janio M. , Alves Sydney H. , Pereira Daniela I. B. , Cavalheiro Ayrton S. , Spanamberg Andréia , Ferreiro Laerte
Published: December 2007

We evaluated the in vitro activities of voriconazole, itraconazole, and terbinafine against 30 clinical isolates of
Pythium insidiosum
using a checkerboard macrodilution method. The combined activity of terbinafine plus itraconazole or plus voriconazole was synergic against 17% of the strains. Antagonism was not observed.
Cidofovir and (S)-9-[3-Hydroxy-(2-Phosphonomethoxy)Propyl]Adenine Are Highly Effective Inhibitors of Vaccinia Virus DNA Polymerase When Incorporated into the Template Strand
Authors: Magee Wendy C. , Aldern Kathy A. , Hostetler Karl Y. , Evans David H.
Published: December 2007

The acyclic nucleoside phosphonate drug (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine [(S)-HPMPA], is a broad-spectrum antiviral and antiparasitic agent. Previous work has shown that the active intracellular metabolite of this compound, (S)-HPMPA diphosphate [(S)-HPMPApp], is an analog of dATP and targets DNA polymerases. However, the mechanism by which (S)-HPMPA inhibits DNA polymerases remains elusive. Using vaccinia virus as a model system, we have previously shown that cidofovir diphosphate (CDVpp), an analog of dCTP and a related antiviral agent, is a poor substrate for the vaccinia virus DNA polymerase and acts to inhibit primer extension and block 3′-to-5′ proofreading exonuclease activity. Based on structural similarities and the greater antiviral efficacy of (S)-HPMPA, we predicted that (S)-HPMPApp would have a similar, but more pronounced effect on vaccinia polymerase than CDVpp. Interestingly, we found that (S)-HPMPApp is a good substrate for the viral enzyme, exhibitingKmandVmaxparameters comparable to those of dATP, and certainly not behaving like CDVpp as a functional chain terminator. Metabolic experiments indicated that (S)-HPMPA is converted to (S)-HPMPApp to a much greater extent than CDV is converted to CDVpp, although both drugs cause identical effects on virus DNA replication at their 50% effective concentration. Subsequent studies showed that both compounds can be faithfully incorporated into DNA, but when CDV and (S)-HPMPA are incorporated into the template strand, both strongly inhibittrans-lesion DNA synthesis. It thus appears that nucleoside phosphonate drugs exhibit at least two different effects on DNA polymerases depending upon in what form the enzyme encounters the drug.
Posaconazole Activity against
Candida glabrata
after Exposure to Caspofungin or Amphotericin B
Authors: Spreghini Elisabetta , Maida Carmelo Massimo , Milici Maria Eleonora , Scalise Giorgio , Barchiesi Francesco
Published: December 2007

We evaluated the effects of sequential therapy with caspofungin (CAS) or amphotericin B (AMB) followed by posaconazole (POS) against
Candida glabrata
. The susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical to those of untreated cells as shown by standard Clinical and Laboratory Standards Institute broth dilution, cell viability, and disk diffusion methods. We then investigated the activity of sequential regimens in an experimental model of disseminated candidiasis. CAS given at 1 mg/kg/day for 2 days followed by POS at either 15 or 30 mg/kg/day significantly reduced the counts compared to the controls, but this treatment was not superior to the use of CAS alone. Also, sequential regimens with AMB given at 1 mg/kg/day for 2 days followed by POS (AMB/POS) were effective at reducing the fungal burden against the controls. In addition, AMB/POS with both doses of the triazole were significantly more effective than AMB alone. Overall, our data showed that there is no therapeutic advantage in using CAS followed by POS, whereas an induction therapy with AMB followed by a maintenance regimen with POS might be a suitable strategy in managing
C. glabrata
infections.
Listeria monocytogenesDesensitizes Immune Cells to Subsequent Ca2+Signaling via Listeriolysin O-Induced Depletion of Intracellular Ca2+Stores
Authors: Gekara Nelson O. , Groebe Lothar , Viegas Nuno , Weiss Siegfried
Published: December 2007

Listeriolysin O (LLO), the pore-forming toxin ofListeria monocytogenes, is a prototype of the cholesterol-dependent cytolysins (CDCs) secreted by several pathogenic and nonpathogenic gram-positive bacteria. In addition to mediating the escape of the bacterium into the cytosol, this toxin is generally believed to be a central player in host-pathogen interactions duringL.monocytogenesinfection. LLO triggers the influx of Ca2+into host cells as well as the release of Ca2+from intracellular stores. Thus, many of the cellular responses induced by LLO are related to calcium signaling. Interestingly, in this study, we report that prolonged exposure to LLO desensitizes cells to Ca2+mobilization upon subsequent stimulations with LLO. Cells preexposed to LLO-positiveL.monocytogenesbut not to the LLO-deficient Δhlymutant were found to be highly refractory to Ca2+induction in response to receptor-mediated stimulation. Such cells also exhibited diminished Ca2+signals in response to stimulation with LLO and thapsigargin. The presented results suggest that this phenomenon is due to the depletion of intracellular Ca2+stores. The ability of LLO to desensitize immune cells provides a significant hint about the possible role played by CDCs in the evasion of the immune system by bacterial pathogens.
Chronic late-gestation hypoglycemia upregulates hepatic PEPCK associated with increased PGC1α mRNA and phosphorylated CREB in fetal sheep
Authors: Rozance Paul J. , Limesand Sean W. , Barry James S. , Brown Laura D. , Thorn Stephanie R. , LoTurco Dan , Regnault Timothy R. H. , Friedman Jacob E. , Hay William W.
Published: December 2007

Hepatic glucose production is normally activated at birth but has been observed in response to experimental hypoglycemia in fetal sheep. The cellular basis for this process remains unknown. We determined the impact of 2 wk of fetal hypoglycemia during late gestation on enzymes responsible for hepatic gluconeogenesis, focusing on the insulin-signaling pathway, transcription factors, and coactivators that regulate gluconeogenesis. Hepatic phospho enolpyruvate carboxykinase and glucose-6-phosphatase mRNA increased 12-fold and 7-fold, respectively, following chronic hypoglycemia with no change in hepatic glycogen. Chronic hypoglycemia decreased fetal plasma insulin with no change in glucagon but increased plasma cortisol 3.5-fold. Peroxisome proliferator-activated receptor-γ coactivator-1α mRNA and phosphorylation of cAMP response element binding protein at Ser133 were both increased, with no change in Akt, forkhead transcription factor FoxO1, hepatocyte nuclear factor-4α, or CCAAT enhancer binding protein-β. These results demonstrate that chronic fetal hypoglycemia triggers signals that can activate gluconeogenesis in the fetal liver.
Is Australia Faking It? The Kyoto Protocol and the Greenhouse Policy Challenge
Authors: Crowley Kate
Published: December 2007

While Australia has signed both the UN Framework Convention on Climate Change, and the Kyoto Protocol to the United Nations Framework Convention on Climate Change, it has failed to ratify the latter. It is nevertheless committed to meeting its +8% Kyoto target for greenhouse gas emissions, and argues that it is on track to doing so. This paper examines Australia's non-ratification politics and greenhouse policy efforts in an attempt to explain its contrary position of resisting Kyoto, yet embracing and pursuing its emission reduction targets. Australia's behavior as a carbon-intensive nation is highly significant in the global context, and this paper focuses on the domestic factors of interests, ideas and institutions, while also considering international factors in trying to explain Australia's non-ratification of Kyoto and climate change policy development. It finds that while ideas and institutions have been modifying influences in the domestic context, political and economic interests have dominated Australia's greenhouse policy.
Multi-Level Reinforcement: Explaining European Union Leadership in Climate Change Mitigation
Authors: Schreurs Miranda A. , Tiberghien Yves
Published: December 2007

The European Union has played a leading role in pushing for the establishment, ratification, and meaningful implementation of the Kyoto Protocol to the United Nations Framework Convention on Climate Change, although it still has significant efforts to make to achieve its target of an 8 percent cut of greenhouse gas by 2008–2012 relative to the 1990 level. This article explores the political factors behind continued EU leadership in climate change. It argues that a few individual states (including Sweden, the Netherlands, Denmark, Germany, and the UK) played an essential role in establishing the EU's agenda in this domain. However, the decentralized governance structure of the EU has also encouraged a process of mutual reinforcement, whereby individual states, the European Commission, and the European Parliament are competing for leadership.
High Noon in Japan: Embedded Symbolism and Post-2001 Kyoto Protocol Politics
Authors: Tiberghien Yves , Schreurs Miranda A.
Published: December 2007

In 2001, the Japanese government committed to ratify the Kyoto Protocol to the United Nations Framework Convention on Climate Change against industry pressures and in spite of the US decision to withdraw from the agreement. This commitment was crucial for the survival of the protocol. Japan has subsequently introduced substantial—yet, mostly voluntary—measures. To explain the puzzle of Japan's ratification, this article builds upon the agenda-setting literature and advances the concept of embedded symbolism. During the 1990s, political leaders elevated climate change and the Kyoto Protocol to the level of a national symbol. Thus, although in 2001 successful implementation of the Kyoto target looked extremely difficult and industry opposition was strong, the symbolism of Kyoto backed by strong public support tipped the balance in favor of ratification.
Cerebral Lateralization of Frontal Lobe Language Processes and Lateralization of the Posterior Visual Word Processing System
Authors: Cai Qing , Lavidor Michal , Brysbaert Marc , Paulignan Yves , Nazir Tatjana A.
Published: December 2007

The brain areas involved in visual word processing rapidly become lateralized to the left cerebral hemisphere. It is often assumed this is because, in the vast majority of people, cortical structures underlying language production are lateralized to the left hemisphere. An alternative hypothesis, however, might be that the early stages of visual word processing are lateralized to the left hemisphere because of intrinsic hemispheric differences in processing low-level visual information as required for distinguishing fine-grained visual forms such as letters. If the alternative hypothesis was correct, we would expect posterior occipito-temporal processing stages still to be lateralized to the left hemisphere for participants with right hemisphere dominance for the frontal lobe processes involved in language production. By analyzing event-related potentials of native readers of French with either left hemisphere or right hemisphere dominance for language production (determined using a verb generation task), we were able to show that the posterior occipito-temporal areas involved in visual word processing are lateralized to the same hemisphere as language production. This finding could suggest top-down influences in the development of posterior visual word processing areas.
Syntactic and Thematic Constraint Effects on Blood Oxygenation Level Dependent Signal Correlates of Comprehension of Relative Clauses
Authors: Caplan David , Stanczak Louise , Waters Gloria
Published: December 2007

The effects of plausibility of thematic role assignment and syntactic structure on blood oxygenation level dependent (BOLD) signal were studied using event-related functional magnetic resonance imaging by orthogonally varying syntactic structure (subject-vs. object-extracted relative clauses) and the plausibility of nouns playing thematic roles (constrained vs. unconstrained sentences) in a plausibility judgment task. In plausible sentences, BOLD signal increased for object-compared to subject-extracted clauses in unconstrained sentences in left middle temporal and left inferior frontal areas, for this contrast in constrained sentences in left middle temporal but not left inferior frontal areas, and for constrained subject-extracted sentences compared to unconstrained subject-extracted sentences in the left inferior frontal gyrus and the left dorsolateral prefrontal cortex. We relate these areas of activation to the assignment of the syntactic structure of object-compared to subject-extracted structures and the process of checking which thematic roles activated in the course of processing a sentence are licensed by the syntactic structure of the sentence.
Distinct Processing of Objects and Faces in the Infant Brain
Authors: Southgate Victoria , Csibra Gergely , Kaufman Jordy , Johnson Mark H.
Published: December 2007

Previous work has shown that gamma-band electroencephalogram oscillations recorded over the posterior cortex of infants play a role in maintaining object representations during occlusion. Although it is not yet known what kind of representations are reflected in these oscillations, behavioral data suggest that young infants maintain spatiotemporal (but not featural) information during the occlusion of graspable objects, and surface feature (but not spatiotemporal) information during the occlusion of faces. To further explore this question, we presented infants with an occlusion paradigm in which they would, on half of the trials, see surface feature violations of either a face or an object. Based on previous studies, we predicted higher gamma-band activation when infants were presented with a surface feature violation of a face, but not of an object. These results were confirmed. A further analysis revealed that whereas infants exhibited a significant increase in gamma during the occlusion of an object (as reported in previous studies), no such increase was evident during the occlusion of a face. These data suggest markedly different processing of objects and faces in the infant brain and, furthermore, indicate that the representation underpinned by the posterior gamma increase may contain only spatiotemporal information.
Cell biology comes to the bedside
Authors: Martin Paul J.
Published: December 2007

Developments from studies of cell biology are beginning to offer improved methods for clinical diagnosis, evaluation, and management of graft-versus-host disease (GVHD), especially for measuring severity and response to treatment.
Adeno-associated virus (AAV)-mediated suppression of Ca2+/calmodulin kinase IV activity in the nucleus accumbens modulates emotional behaviour in mice
Authors: Schneider Miriam , Spanagel Rainer , Zhang Sheng-Jia , Bading Hilmar , Klugmann Matthias
Published: December 2007

Background

Calcium/calmodulin-dependent protein kinase IV (CaMKIV) controls activity-dependent gene transcription by regulating the activity of the cyclic AMP response element binding protein (CREB). This signaling pathway is involved in gating emotional responses in the CNS but previous studies did not address the potential roles of CaMKIV in discrete brain regions. In the present study, we aimed at specifically dissecting the role of CaMKIV in the nucleus accumbens of adult mice.

Results

We used recombinant adeno-associated virus (rAAV)-mediated gene transfer of a dominant-negative CaMKIV variant (rAAV-dnCaMKIV) to inhibit endogenous CaMKIV in the nucleus accumbens. rAAV-dnCaMKIV treated animals were subjected to a battery of tests including, prepulse inhibition of the acoustic startle response, open field, social interaction and anxiety-related behaviour. We found that basal locomotor activity in the open field, and prepulse inhibition or startle performance were unaltered in mice infected with rAAV-dnCaMKIV in the nucleus accumbens. However, anxiogenic effects were revealed in social interaction testing and the light/dark emergence test.

Conclusion

Our findings suggest a modulatory role of CaMKIV in the nucleus accumbens in anxiety-like behaviour but not sensorimotor gating.
Impact of estrogen receptor gene polymorphisms and mRNA levels on obesity and lipolysis – a cohort study
Authors: Nilsson Maria , Dahlman Ingrid , Jiao Hong , Gustafsson Jan-Åke , Arner Peter , Dahlman-Wright Karin
Published: December 2007

Background

The estrogen receptors α and β (ESR1, ESR2) have been implicated in adiposity, lipid metabolism and feeding behaviour. In this report we analyse ESR1 and ESR2 gene single nucleotide polymorphisms (SNPs) for association with obesity. We also relate adipose tissue ESR1 mRNA levels and ESR1 SNPs to adipocyte lipolysis and lipogenesis phenotypes.

Methods

23 ESR1 and 11 ESR2 tag-SNPs, covering most of the common haplotype variation in each gene according to HAPMAP data, were analysed by Chi2 for association with obesity in a cohort comprising 705 adults with severe obesity and 402 lean individuals. Results were replicated in a cohort comprising 837 obese and 613 lean subjects. About 80% of both cohorts comprised women and 20% men. Adipose tissue ESR1 mRNA was quantified in 122 women and related to lipolysis and lipogenesis by multiple regression. ESR1 SNPs were analysed for association with adipocyte lipolysis and lipogenesis phenotypes in 204 obese women by simple regression.

Results

No ESR1 SNP was associated with obesity. Five ESR2 SNPs displayed nominal significant allelic association with obesity in women and one in men. The two ESR2 SNPs associated with obesity with nominal P value < 0.01 were genotyped in a second cohort where no association with obesity was observed. There was an inverse correlation between ESR1 mRNA levels in abdominal subcutaneous (sc) adipose tissue and basal lipolysis, as well as responsiveness to adrenoceptor agonists independent of age and BMI (P value 0.009–0.045). ESR1 rs532010 was associated with lipolytic sensitivity to noradrenaline (nominal P value 0.012), and ESR1 rs1884051 with responsiveness to the non-selective beta-adrenoceptor agonist isoprenaline (nominal P value 0.05). These associations became non-significant after Bonferroni correction.

Conclusion

ESR1 gene alleles are unlikely to be a major cause of obesity in women. A minor importance of ESR2 on severe obesity cannot be excluded. The inverse correlation between ESR1 mRNA levels and lipolytic responsiveness to adrenoceptor agonists implies that low adipose tissue ESR1 levels attenuate catecholamine resistance in sc fat cells of obese women hereby contributing to loss of sc and gain of visceral fat. There is no evidence for a genetic impact of ESR1 on lipolysis or lipogenesis.
Increased serum levels of TGFβ1 in children with localized scleroderma
Authors: Uziel Yosef , Feldman Brian M , Krafchik Bernice R , Laxer Ronald M , Yeung Rae SM
Published: December 2007

Background

There are neither sensitive nor specific laboratory tests for measuring disease activity in localized scleroderma (LS). Monitoring is done almost exclusively by clinical assessment. Our aim was to determine whether serum concentrations of TGFβ1 are a good biomarker of disease activity in children with LS.

Methods

55 pediatric patients with LS were divided into sub-types according to their main lesion; morphea, generalized morphea, linear scleoderma affecting a limb or the face. The lesions were further categorized by overall clinical assessment into active, inactive, and indeterminate groups according to disease activity. Serum TGFβ1 concentration levels were measured by enzyme linked immunosorbent assay (ELISA), analyzed and correlated with disease subtypes and disease activity.

Results

The mean TGFβ1 concentration were significantly higher in the patient group (51393 ± 33953 pg/ml) than in the control group (9825 ± 5287 pg/ml) (P < 0.001). The mean concentration were elevated in all the disease subtypes, and did not correlate with disease duration or activity.

Conclusion

Serum concentration of TGFβ1 were elevated in patients with all subtypes of LS irrespective of clinical disease activity. Although TGFβ1 may play an important role in the pathogenesis of local skin fibrosis, circulating blood levels of molecules known to act locally may not be useful biomarkers of disease activity.
Determination of suitable housekeeping genes for normalisation of quantitative real time PCR analysis of cells infected with human immunodeficiency virus and herpes viruses
Authors: Watson Sarah , Mercier Sarah , Bye Chris , Wilkinson John , Cunningham Anthony L , Harman Andrew N
Published: December 2007

The choice of an appropriate housekeeping gene for normalisation purposes has now become an essential requirement when designing QPCR experiments. This is of particular importance when using QPCR to measure viral and cellular gene transcription levels in the context of viral infections as viruses can significantly interfere with host cell pathways, the components of which traditional housekeeping genes often encode. In this study we have determined the reliability of 10 housekeeping genes in context of four heavily studied viral infections; human immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus and varicella zoster virus infections using a variety of cell types and virus strains. This provides researchers of these viruses with a shortlist of potential housekeeping genes to use as normalisers for QPCR experiments.
Modifiable risk factors remain significant causes of medium term mortality after first time Coronary artery bypass grafting
Authors: Kunadian Babu , Dunning Joel , Millner Russell W. J.
Published: December 2007

Background

Whilst there is much current data on early outcomes after Coronary artery bypass grafting(CABG), there is relatively little data on medium term outcomes in the current era. The purpose of this study is to present a single surgeon series comprising of all first time CABG patients operated on with the technique of cross clamp fibrillation from Feb-1996 to through to Jan-2003, and to seek risk factors for medium term mortality in these patients.

Methods

Data was collected from Hospital Episode Statistics and departmental patient administration and tracking systems and cross checked using database techniques. Patient outcomes were searched using the National Health Service strategic tracing service.

Results

Mean follow up was 5.3 years(0–9.4 years) and was complete for all patients. 30-day survival was 98.4%, 1-year survival 95% and 8-year survival 79%. Cox-regression analysis revealed that several modifiable pre-operative risk factors remain significant predictors of medium term mortality, including Diabetes(Hazard Ratio(HR) 1.73, 95%CI 1.21–2.45), Chromic obstructive pulmonary disease(HR 2.02, 95%CI 1.09–3.72), Peripheral vascular disease(HR 1.68, 95%CI 1.13–2.5), Body mass index>30(HR 1.54, 95%CI 1.08–2.20) and current smoker at operation(HR 1.67, 95%CI 1.03–2.72). However hypertension(HR 1.31, 95%CI 0.95–1.82) and Hypercholestrolaemia(HR 0.81, 95%CI 0.58–1.13) were not predictive which may reflect adequate post-operative control.

Conclusion

Coronary artery bypass surgery using cross clamp fibrillation is associated with a very low operative mortality. Medium term survival is also good but risk factors such as smoking at operation, Chronic obstructive pulmonary disease, obesity and diabetes negatively impact this survival and should be aggressively treated in the years post-surgery.