bluuebunny/crossref_metadata_2025 huggingface dataset:
CD300a and CD300f differentially regulate the MyD88 and TRIF‐mediated TLR signalling pathways through activation of SHP‐1 and/or SHP‐2 in human monocytic cell lines
Authors: Kim Eun‐Ju , Lee Sang‐Min , Suk Kyoungho , Lee Won‐Ha
Published: October 2011

CD300a, a membrane protein expressed on myeloid lineages and specific subsets of CD4+ T cells, has been reported to have inhibitory activities in cellular activation. However, the role of CD300a in Toll‐like receptor (TLR) ‐mediated macrophage activation has not been investigated. The human monocytic cell lines THP‐1 and U937 were stimulated with various TLR ligands after triggering of CD300a with specific monoclonal antibody. Interestingly, CD300a blocked TLR4‐mediated and TLR9‐mediated expression of pro‐inflammatory mediators without affecting TLR3‐mediated events. In contrast, CD300f, another member of the CD300 family, blocked the activation of cells induced by all TLR ligands. A transient transfection assay using luciferase reporter gene under the regulation of nuclear factor‐κB binding sites indicated that co‐transfection of CD300f blocked reporter expression induced by over‐expression of both myeloid differentiation factor 88 (MyD88) and toll‐interleukin 1 receptor‐domain‐containing adapter‐inducing interferon‐β (TRIF), whereas CD300a blocked only MyD88‐induced events. Synthetic peptides representing immunoreceptor tyrosine‐based inhibitory motifs of CD300a or CD300f mimicked the differential inhibition patterns of their original molecules. The use of various signalling inhibitors and Western blotting analysis revealed that TLR9/MyD88‐mediated signalling was regulated mainly by SH2‐containing tyrosine phosphatase 1 (SHP‐1), which could be activated by CD300a or CD300f. In contrast, regulation of the TLR3/TRIF‐mediated pathway required the combined action of SHP‐1 and SHP‐2, which could be accomplished by CD300f but not CD300a. These data indicate that CD300a and CD300f regulate the MyD88 and TRIF‐mediated TLR signalling pathways through differential activation of SHP‐1 and SHP‐2.
Insights gained from modelling high‐grade glioma in the mouse
Authors: Rankin S. L. , Zhu G. , Baker S. J.
Published: October 2011

S. L. Rankin, G. Zhu and S. J. Baker (2012) Neuropathology and Applied Neurobiology38, 254–270

Insights gained from modelling high‐grade glioma in the mouse

High‐grade gliomas (HGGs) are devastating primary brain tumours with poor outcomes. Advances towards effective treatments require improved understanding of pathogenesis and relevant model systems for preclinical testing. Mouse models for HGG provide physiologically relevant experimental systems for analysis of HGG pathogenesis. There are advantages and disadvantages to the different methodologies used to generate such models, including implantation, genetic engineering or somatic gene transfer approaches. This review highlights how mouse models have provided insights into the contribution of specific mutations to tumour initiation, progression and phenotype, the influence of tumour micro‐environment, and the analysis of cell types that can give rise to glioma. HGGs are a heterogeneous group of tumours, and the complexity of diverse mutations within common signalling pathways as well as the developmental and cell‐type context of transformation contributes to the overall diversity of glioma phenotype. Enhanced understanding of the mutations and cell types giving rise to HGG, along with the ability to design increasingly complex mouse models that more closely simulate the process of human gliomagenesis will continue to provide improved experimental systems for dissecting mechanisms of disease pathogenesis and for preclinical testing.
HPR1, a component of the THO/TREX complex, plays an important role in disease resistance and senescence in Arabidopsis
Authors: Pan Huairong , Liu Simu , Tang Dingzhong
Published: October 2011

ENHANCED DISEASE RESISTANCE 1 (EDR1) is a negative regulator of powdery mildew resistance, cell death and ethylene‐induced senescence. To identify components involved in EDR1 signaling, we performed a forward genetic screen for edr1 suppressors. In this screen, we identified the hpr1‐4 mutation, which partially suppresses edr1‐mediated resistance to the powdery mildew pathogen Golovinomyces cichoracearum and mildew‐induced cell death. However, the hpr1‐4 mutation enhanced the ethylene‐induced senescence phenotype of edr1. The hpr1‐4 single mutant displayed enhanced susceptibility to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and the oomycete pathogen Hyaloperonospora arabidopsidis Noco2. Arabidopsis HPR1 encodes a homolog of human HPR1, a component of the conserved THO/transcription export (THO/TREX) complex that is required for mRNA export in yeast and humans. HPR1 is expressed in various organs and throughout all developmental stages. HPR1 localizes to the nucleus, and, significantly, mRNA export is compromised in the hpr1‐4 mutant. Taken together, these data demonstrate that HPR1 plays an important role in disease resistance in plants, and that the THO/TREX complex is functionally conserved among plants, yeast and humans. Our data indicate a general link between mRNA export, defense responses and ethylene signaling in plants.
A tonoplast‐localized half‐size ABC transporter is required for internal detoxification of aluminum in rice
Authors: Huang Chao‐Feng , Yamaji Naoki , Chen Zhichang , Ma Jian Feng
Published: October 2011

Toxic aluminum enters the root cells rapidly, therefore internal detoxification is required. However, the molecular mechanisms underlying this process are poorly understood. Here we functionally characterized a rice gene, Os03g0755100 (OsALS1), that is regulated by ART1, a C2H2‐type zinc finger transcription factor. OsALS1 encodes a half‐size ABC transporter that is a member of the TAP (transporter associated with antigen processing) sub‐group. Expression of OsALS1 was rapidly and specifically induced by Al in the roots, but not by other metals or low pH. OsALS1 was localized at all cells of the roots. Furthermore, OsALS1 is localized to the tonoplast. These expression patterns and cell specificity of localization are different from those of the homologous gene AtALS1 in Arabidopsis. Knockout of OsALS1 in three independent lines resulted in significant increased sensitivity to Al, but did not affect the sensitivity to other metals and low pH. Comparison of Al accumulation patterns between wild‐type and osals1 mutants showed that there was no difference in Al levels in the cell sap of root tips between wild‐type and the mutants, but the mutants accumulated more Al in the cytosol and nucleus than the wild‐type. Expression of OsALS1 in yeast resulted in increased Al sensitivity due to mis‐localization. These results indicate that OsALS1 localized at the tonoplast is responsible for sequestration of Al into the vacuoles, which is required for internal detoxification of Al in rice.
A c.3216_3217delGA mutation in AGL gene in Tunisian patients with a glycogen storage disease type III: evidence of a founder effect
Authors: Mili A , Ben Charfeddine I , Amara A , Mamaï O , Adala L , Ben Lazreg T , Bouguila J , Saad A , Limem K , Gribaa M
Published: October 2011

Mili A, Ben Charfeddine I, Amara A, MamaÏ O, Adala L, Ben Lazereg T, Bougulia J, Saad A, Limem K, Gribaa M. A c.3216_3217delGA mutation in AGL gene in Tunisian patients with a glycogen storage disease type III: evidence of a founder effect.

Glycogen storage disease type III (GSD III) is an autosomal recessive disorder characterized by excessive accumulation of abnormal glycogen in the liver and muscles and caused by deficiency in the glycogen debranching enzyme, the amylo‐1,6‐glucosidase (AGL). In this study, we report the clinical, biochemical and genotyping features of five unrelated GSD III patients coming from the same region in Tunisia. The concentration of erythrocyte glycogen and AGL activity were measured by colorimetric and fluorimetric methods, respectively. Four CA/TG microsatellite markers flanking the AGL gene in chromosome 1 were amplified with fluoresceinated primers. The full coding exons and their relevant exon–intron boundaries of the AGL gene were directly sequenced for the patients and their parents. All patients showed a striking increase of erythrocytes glycogen content. No AGL activity was detected in peripheral leukocytes. Sequencing of the AGL gene identified a c.3216_3217delGA (p.Glu1072AspfsX36) mutation in the five patients which leads to a premature termination, abolishing the AGL activity. Haplotype analysis showed that the mutation was associated with a common homozygote haplotype. Our results suggested the existence of a founder effect responsible for GSD III in this region of Tunisia.
Clinical impact of the use of 16S rRNA sequencing method for the identification of “difficult‐to‐identify” bacteria in immunocompromised hosts
Authors: Bharadwaj R. , Swaminathan S. , Salimnia H. , Fairfax M. , Frey A. , Chandrasekar P.H.
Published: October 2011

Molecular method of 16S rRNA sequencing is reported to be helpful in the accurate identification of organisms with ambiguous phenotypic profiles. We analyzed the use of 16S rRNA sequencing method to identify clinically significant, “difficult‐to‐identify” bacteria recovered from clinical specimens, and evaluated its role in patient management and consequent clinical outcome. Among the 172 “difficult‐to‐identify” bacteria recovered over a 4‐year period, 140 were gram‐positive cocci or gram‐negative bacilli; identification by 16S rRNA did not play a role in the management of patients infected with these bacteria. From 32 patients, 33 “difficult‐to‐identify” gram‐positive bacilli were identified; the organisms were mycobacteria, Nocardia, Tsukamurella, Rhodococcus, and Gordonia. In 24 patients for whom clinical data were available, results from the 16S rRNA sequencing method led to treatment change in 14 immunocompromised patients (including 7 hematopoietic stem cell recipients and 1 liver transplant recipient). Therapy was modified in 9 patients, initiated in 3 patients, and discontinued in 2 patients. Most patients’ therapy was switched to oral antibiotics with discontinuation of intravascular catheters, facilitating early hospital discharge. All 14 patients were alive 30 days after infection onset. The present study demonstrates the clinical application of 16S rRNA sequencing method to identify “difficult‐to‐identify” mycobacteria and other gram‐positive bacilli in clinical specimens, particularly in immunocompromised hosts.
Infection with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae in solid organ transplantation
Authors: Bergamasco M.D. , Barroso Barbosa M. , de Oliveira Garcia D. , Cipullo R. , Moreira J.C.M. , Baia C. , Barbosa V. , Abboud C.S.
Published: October 2011

Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae is spreading globally and represents a challenge in infection control and treatment. Solid organ transplant (SOT) recipients are especially at risk for infection by multidrug‐resistant bacteria, and little is known about infection with KPC‐producing organisms in this setting. The aim of this study was to describe the clinical and microbiologic aspects of KPC‐producing K. pneumoniae infections in SOT recipients. A KPC‐2‐producing K. pneumoniae outbreak was identified in a public teaching tertiary care hospital in São Paulo, Brazil, in June 2009. During the outbreak, cases of KPC‐2‐producing K. pneumoniae infection in SOT recipients occurred between July 2009 and February 2010; these cases were retrospectively reviewed. Overall, 12 episodes of infection with KPC‐producing K. pneumoniae occurred in 2 heart, 4 liver, and 6 kidney transplant recipients with incidence rates of 16.7%, 12.9%, and 26.3% in heart, liver, and kidney transplantation, respectively. Infection occurred at a median time of 20 days after transplantation. Primary infection sites were as follows: 4 urinary tract infections, 4 bloodstream infections, 2 pneumonias, and 2 surgical site infections. All patients except one had received antibiotics in the last 30 days, mostly piperacillin‐tazobactam or glycopeptides. All strains exhibited susceptibility to amikacin and gentamicin. Patients were treated with tigecycline plus polymyxin B (3 cases), polymyxin B plus carbapenem (3 cases), polymyxin B alone (3 cases), or tigecycline plus imipenem (1 case). In 2 cases, patients received only carbapenem, and death occurred before the final culture result. The overall 30‐day mortality rate was 42%. In this series of KPC‐producing K. pneumoniae infection in SOT recipients, the infection occurrence was high during an institutional outbreak and was potentially life threatening.
Oral valganciclovir versus ganciclovir as delayed pre‐emptive therapy for patients after allogeneic hematopoietic stem cell transplant: a pilot trial (04‐0274) and review of the literature
Authors: Chawla J.S. , Ghobadi A. , Mosley J. , Verkruyse L. , Trinkaus K. , Abboud C.N. , Cashen A.F. , Stockerl‐Goldstein K.E. , Uy G.L. , Westervelt P. , DiPersio J.F. , Vij R.
Published: October 2011

Background

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). This pilot prospective randomized clinical trial compares valganciclovir (VGV) to ganciclovir (GCV) as pre‐emptive therapy for CMV viremia in the post‐allogeneic HSCT population.

Methods

Patients undergoing allogeneic HSCT who were at risk for CMV viremia were monitored post HSCT by weekly quantitative whole blood polymerase chain reaction. Pre‐emptive therapy was delayed until the viral load (VL) was >10,000 copies/mL once, or >5000 copies/mL twice. Patients were randomized to either GCV 5 mg/kg twice a day (b.i.d.) for 7 days followed by daily GCV 5 mg/kg for up to 21 days, or VGV 900 mg b.i.d. for 7 days followed by 900 mg daily for up to 21 days. The primary endpoint was clearance of viremia (VL <5000 copies/mL) within 28 days of initiation of therapy.

Result

In total, 37 patients were enrolled; 19 patients received treatment with VGV and 18 patients received treatment with GCV. The VGV was not inferior in efficacy to GCV as pre‐emptive therapy, with rates of viral clearance at 28 days of 89.5% and 83%, respectively (P‐value for non‐inferiority = 0.030). Toxicities were similar between the 2 arms. No patients developed CMV disease.

Conclusions

In this trial, the rates of clearance of viremia appear to be similar with VGV and GCV.
Egg yolk fatty acid profile of avian species – influence on human nutrition
Authors: Golzar Adabi SH. , Ahbab M. , Fani A. R. , Hajbabaei A. , Ceylan N. , Cooper R. G.
Published: October 2011

Lipids are an important nutritional component of the avian egg. A review of the literature was completed to determine the fatty acid compositions in egg yolk from some avian species. Additionally, the nutritional influence of lipid and lipoprotein content on the plasma of male participants during 30‐day feeding was discussed. The ostrich eggs had the highest unsaturated fatty acid and the lowest cholesterol content in relation to other avian species. Ostrich had a higher proportion of 18:3n‐3 (p < 0.01) compared with other species. Chicken yolk numerically contained much higher levels of 22:6n‐3 than those found in turkeys, quails and geese, but the amount of 22:6n‐3 in ostrich egg was lower by comparison with other species (p < 0.01). After the storage of eggs at the room temperature, there was a notable loss of vitamin E (vitE) in the yolks of all species and this decrease was marginal (p < 0.01) in ostrich compared with other species. There were significant (p < 0.05) increases in plasma low‐density lipoprotein (LDL) level in all male subjects. Plasma high‐density lipoprotein (HDL) level decreased (p < 0.05) only in men who were fed chicken or ostrich eggs daily. Consumption of different species’ eggs had no influence on the total male plasma cholesterol and triglyceride levels. LDL‐C:HDL‐C ratio increased (p < 0.05) after goose and turkey egg consumption. Consumption of one egg/month by healthy human subjects had no effect on serum total cholesterol and triglyceride. The LDL‐C:HDL‐C ratio (which is a strong predictor of coronary heart disease risk) increased, although non‐significantly, by consuming chicken, quail and ostrich eggs.
Fas Expression and Mediated Activation of an Apoptosis Programme in Bovine Follicular Granulosa Cells In Vitro
Authors: Yang RJ , Li JY , Zhao ZH , Gao X , Gao HJ , Xu SZ
Published: October 2011

Contents

The Fas antigen is a transmembrane receptor that can trigger apoptosis in a variety of somatic cells. Ovarian follicular atresia and luteolysis are thought to occur by apoptosis. To reveal the intracellular signal transduction molecules involved in the process of follicular development in the bovine ovary, Fas gene without the stop codon was amplified in the present study using RT‐PCR and directly cloned into the eukaryotic expression vector pAcGFP‐N1. The resultant recombinant plasmid pAcGFP‐bFas was then transfected into bovine follicular granulosa cells. Expression of AcGFP was observed under fluorescent microscopy, and the transcription and translation of Fas were detected by RT‐PCR and western blot analysis. The methyl‐tetrazolium (MTT) assay, Hoechst33342 staining and DNA ladder method were performed to determine the growth inhibition and apoptosis of the cells. The results showed that GFP expression was detected as early as 24 h after transfection. The Fas fusion gene was successfully expressed in granulosa cells as evidenced by the detection of a 994‐bp fragment corresponding to the Fas mRNA by RT‐PCR and a 64.5‐kD band corresponding to the Fas fusion protein by western blot. Granulosa cell viability decreased significantly at 72 h after transfection, and the apoptosis rate of the cells transfected with pAcGFP‐Fas was significantly higher than that of the control group. Cells in the Fas transfection group showed ladder patterns characteristic of apoptosis, and the nuclei were shrunken and densely hyperchromatic or fragmented, suggesting that Fas is capable of inhibiting the proliferation of bovine follicular granulosa cells and inducing cell apoptosis when over‐expressed. This study will aid in further understanding the mechanism of regulation of Fas on bovine oocyte formation and development.
Carcinoid tumor arising in a thymic bronchogenic cyst associated with thymic follicular hyperplasia
Authors: Tsai Jia‐Huei , Lee Jang‐Ming , Lin Ming‐Chieh , Liau Jau‐Yu
Published: October 2011

Bronchogenic cysts are congenital malformations of the embryonic tracheobronchial tree and are the most common cause of mediastinal cysts, encountered mainly in pediatric patients and young adults. Conservative treatment has been proposed for asymptomatic patients. However, malignant transformation occurs occasionally and the clinicopathological features of secondary malignancy are not well characterized. In this report, we present a carcinoid tumor found in the thymic bronchogenic cyst of a 41‐year‐old female complaining of mild chest pain. The thymic tissue also shows follicular lymphoid hyperplasia. Atypical imaging features were found in her chest computed tomography. Additional 22 cases of bronchogenic cysts with malignant transformation were also reviewed from the literature. The clinicopathological data were summarized. The tumorigenesis of these tumors is unclear, but bronchogenic cysts of the lung may undergo malignant changes at a younger patient age and more frequently than mediastinal ones. Carcinoid tumors were also seemingly overrepresented in mediastinal cases. Some atypical imaging features may serve as clues for early detection and guide clinical management.
York‐Mason procedure for repair of recto‐urinary fistulae: a 40‐year experience
Authors: Hadley David A. , Southwick Andrew , Middleton Richard G.
Published: October 2011

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

Our previous report, almost 10 years ago, on the York‐Mason procedure was the largest series on this procedure. That report concluded that the York‐Mason posterior, trans‐anal, trans‐rectal correction of iatrogenic recto‐urinary fistula was highly successful, reliable and safe – when employed for small fistulas following prostate surgery. Since then, many other smaller case series have confirmed our success.

This study provides a continuing body of evidence of the success, reliability, and safety by the largest York‐Mason series in the literature, and our numbers have now doubled in less than 10 years. Avoiding preliminary fecal diversion after surgical injury, which we proposed on our previous report, has now been observed to be safe and reliable with long‐term follow up. We also tried to push the limits of the surgery into larger, radiated fishtulas, but unfortunately were met with poorer outcomes.

OBJECTIVE

To review the use of the York‐Mason transanal, transrectal procedure, used in properly selected patients over a 40‐year period, for repairing recto‐urinary fistulae.

PATIENTS AND METHODS

We retrospectively reviewed the medical records of all patients who underwent acquired recto‐urethral or rectovesical fistula repair at our institution.

A total of 51 patients have undergone York‐Mason recto‐urinary fistula repair at our institution during this time.

RESULTS

Since our last report in 2003, we have performed this procedure an additional 27 times.

We continue to have good results, with 25 of these patients having resolution of their fistulae after one procedure.

Failures in the updated cohort were radiation‐induced fistulae.

We continue to find no evidence of faecal incontinence or stenosis after this procedure.

CONCLUSIONS

Over a period of 40 years, the York‐Mason posterior, transanal, transrectal correction of iatrogenic recto‐urinary fistula has been highly successful, reliable and safe, when used for fistulae occurring after prostate surgery.

Preliminary faecal diversion can often be avoided in selected patients.
Focal cryotherapy for localized prostate cancer: a report from the national Cryo On‐Line Database (COLD) Registry
Authors: Ward John F. , Jones J. Stephen
Published: October 2011

Study Type – Therapy (cohort)

Level of Evidence 2b

What's known on the subject? and What does the study add?

Selective destruction of targeted prostate tissue is now technically feasible. Much has been theorized but little is known about the proper patient selection or treatment outcomes to determine if this organ preserving approach to prostate cancer has merit for further study and diffusion into wider practice.

Herein we present the largest retrospective registry report of men treated with sub‐total prostate cryotherapy in order to begin to understand how this treatment is being applied despite the paucity of data.

OBJECTIVES

To identify recent trends in focal cryotherapy from a prospectively maintained treatment registry.

To describe treatment outcomes after uncontrolled application of focally ablative techniques within community practice.

MATERIALS AND METHODS

We conducted an analysis of the COLD Registry to identify patients treated with partial gland prostate cryoablation between 1997 and 2007.

Preoperative characteristics and postoperative cancer‐specific and functional outcomes were assembled for analysis.

RESULTS

The COLD Registry contained information for 5853 patients and focal cryotherapy was the codified procedure in 1160 patients (19.8%).

A dramatic increase in focal treatments was observed, from 46 in 1999 to 567 in 2005 (P < 0.01).

The biochemical recurrence‐free rate (ASTRO definition) at 36 months was 75.7%.

Prostate biopsy, performed in 164/1160 of patients (14.1%), was positive in 43 (26.3%) of those suspected of cancer recurrence, but in only 3.7% (43/1160) of treated patients.

Urinary continence (defined as use of 0 pads) was 98.4%. Maintenance of spontaneous erections was 58.1%. Prolonged urinary retention (>30 days) occurred in six (1.1%) patients. Rectourethral fistula was observed in one (0.1%) patient.

CONCLUSIONS

Focal cryoablation is increasingly used for selected patients with prostate cancer.

Oncological efficacy in the present series appears similar to that of whole‐gland cryoablation.

The impact of focal cryoablation on urinary, sexual and bowel function appears to be less than that of radical therapies, although preservation of sexual function is not as high as might be expected.
Common ancestry or environmental trait filters: cross‐continental comparisons of trait–habitat relationships in tropical anuran amphibian assemblages
Authors: Ernst Raffael , Keller Alexander , Landburg Gwendolyn , Grafe T. Ulmar , Linsenmair K. Eduard , Rödel Mark‐Oliver , Dziock Frank
Published: October 2011

Aim  To investigate whether trait–habitat relations in biological communities converge across three global regions. The goal is to assess the role of habitat templets in shaping trait assemblages when different assembly mechanisms are operating and to test whether trait–habitat relations reflect a common evolutionary history or environmental trait filters.

Location  Guiana Shield, South America; Upper Guinea Forest Block, West Africa; Borneo rain forests, Southeast Asia.

Methods  We compared large anuran amphibian data sets at both the regional and cross‐continental scale. We applied a combination of three‐table ordinations (RLQ) and permutation model‐based multivariate fourth‐corner statistics to test for trait–habitat relationships at both scales and used phylogenetic comparative methods to quantify phylogenetic signal in traits that enter these analyses.

Results  Despite the existence of significant trait–habitat links and congruent trait patterns, we did not find evidence for the existence of a universal trait–habitat relationship at the assemblage level and no clear sign for cross‐continental convergence of trait–habitat relations. Patterns rather varied between continents. Despite the fact that a number of traits were conserved across phylogenies, the phylogenetic signal varied between regions. Trait–habitat relations therefore not only reflect a common evolutionary history, but also more recently operating environmental trait filters that ultimately determine the trait composition in regional assemblages.

Main conclusions  Integrating trait–habitat links into analyses of biological assemblages can enhance the predictive power and general application of species assembly rules in community and macroecology, particularly when phylogenetic comparative methods are simultaneously applied. However, in order to predict trait composition based on habitat templets, trait–habitat links cannot be assumed to be universal but rather have to be individually established in different regions prior to model building. Only then can direct trait‐based approaches be useful tools for predicting fundamental community patterns.
Does causal action facilitate causal perception in infants younger than 6 months of age?
Authors: Rakison David H. , Krogh Lauren
Published: October 2011

Previous research has established that infants are unable to perceive causality until 6¼ months of age. The current experiments examined whether infants’ ability to engage in causal action could facilitate causal perception prior to this age. In Experiment 1, 4½‐month‐olds were randomly assigned to engage in causal action experience via Velcro sticky mittens or not engage in causal action because they wore non‐sticky mittens. Both groups were then tested in the visual habituation paradigm to assess their causal perception. Infants who engaged in causal action – but not those without this causal action experience – perceived the habituation events as causal. Experiment 2 used a similar design to establish that 4½‐month‐olds are unable to generalize their own causal action to causality observed in dissimilar objects. These data are the first to demonstrate that infants under 6 months of age can perceive causality, and have implications for the mechanisms underlying the development of causal perception.
Older and wiser? Men’s and women’s accounts of drinking in early mid‐life
Authors: Emslie Carol , Hunt Kate , Lyons Antonia
Published: October 2011

Most qualitative research on alcohol focuses on younger rather than older adults. To explore older people’s relationship with alcohol, we conducted eight focus groups with 36 men and women aged 35 to 50 years in Scotland, UK. Initially, respondents suggested that older drinkers consume less alcohol, no longer drink to become drunk and are sociable drinkers more interested in the taste than the effects of alcohol. However, as discussions progressed, respondents collectively recounted recent drunken escapades, challenged accounts of moderate drinking, and suggested there was still peer pressure to drink. Some described how their drinking had increased in mid‐life but worked hard discursively to emphasise that it was age and stage appropriate (i.e. they still met their responsibilities as workers and parents). Women presented themselves as staying in control of their drinking while men described going out with the intention of getting drunk (although still claiming to meet their responsibilities). While women experienced peer pressure to drink, they seemed to have more options for socialising without alcohol than did men. Choosing not to drink alcohol is a behaviour that still requires explanation in early mid‐life. Harm reduction strategies should pay more attention to drinking in this age group.
Reading and spelling in adults: are there lexical and sub‐lexical subtypes?
Authors: Burt Jennifer S. , Heffernan Maree E.
Published: October 2011

The dual‐route model of reading proposes distinct lexical and sub‐lexical procedures for word reading and spelling. Lexically reliant and sub‐lexically reliant reader subgroups were selected from 78 university students on the basis of their performance on lexical (orthographic) and sub‐lexical (phonological) choice tests, and on irregular and nonword naming. In spelling of irregular words and nonwords to dictation, the group comparisons failed to support the dissociative predictions for lexical and sub‐lexical reliance that were derived from the dual‐route model: lexical readers were not superior to sub‐lexical readers on spelling irregular words as well as inferior to sub‐lexical readers on spelling regular letter strings (nonwords). In line with a single‐route view, print exposure and phonological coding (nonword naming accuracy) appear to be key factors in the effective learning of both regular and irregular words.
The clinical spectrum of intracerebral hematoma, hemorrhagic infarct, non‐hemorrhagic infarct, and non‐lesional venous stroke in patients with cerebral sinus–venous thrombosis
Authors: Kumral E. , Polat F. , Uzunköprü C. , Çallı C. , Kitiş Ö.
Published: October 2011

Background and purpose:  The clinical spectrum of different neuroradiological features of cerebral sinus–venous thrombosis (CSVT) varies considerably. We sought the relationship between different neuroradiological aspects and clinical presentations in these patients.

Methods:  The diagnosis of cerebral sinus–venous thrombosis has been confirmed by conventional angiography, MRI combined with MR venography following established diagnostic criteria. We analyzed clinical data, symptoms and signs, imaging findings, location and extent of the thrombus, and parenchymal lesions, retrospectively.

Results:  There were 220 consecutive patients with cerebral sinus–venous thrombosis; 98 (45%) had non‐lesional sinus–venous thrombosis (NL CSVT), 51 (23%) had non‐hemorrhagic infarct (NHI), 45 (20%) had hemorrhagic infarct (HI), and 26 (12%) had intracerebral hemorrhage (ICH). In patients with hemorrhagic lesion (HI+ICH), advanced age, headache (99%), behavioral disturbances (55%), consciousness disturbances (35%), seizures (41%), and language deficits (42%) were significantly higher than the other patients (NL+NHI) (P < 0.001). High blood pressure at admission, puerperium, sigmoid and straight sinus thrombosis, multiple sinus and vein involvement were more frequent in patients with hemorrhagic lesion than those with non‐hemorrhagic lesion. Patients with hemorrhagic lesion were more dependent or died (32%) than the other patients (12%) (P < 0.001), and most of the patients with NL and NHI had no disability compared with the other patients at the 3 month of follow‐up (96% and 65%; P < 0.001).

Conclusion:  Headache, convulsion, behavioral disorder, seizures, and speech disorders were the most frequent clinical symptoms of patients with hemorrhagic CSVT. Specific risk factors, including pregnancy/puerberium, early and extended thrombosis of large sinus, and presence of high blood pressure at admission, are associated with hemorrhagic lesion and unfavorable outcome.
Conservation genetics of threatened Mexican axolotls (Ambystoma)
Authors: Parra‐Olea G. , Zamudio K. R. , Recuero E. , Aguilar‐Miguel X. , Huacuz D. , Zambrano L.
Published: October 2011

The loss of genetic diversity in small or isolated populations can increase inbreeding, decrease fitness and adaptive potential and increase a species’ probability of extinction. In species with life histories that naturally result in small populations and/or low levels of gene flow, patterns of anthropogenically induced genetic erosion can be obscured by evolutionary history; yet these species may still be susceptible to genetic loss. We assess genetic diversity among populations of Ambystoma salamanders endemic to Mexico, including populations that are facultatively or obligately paedomorphic, to test whether paedomorphic lineages have lower genetic diversity than metamorphic ones, and whether gene flow contributes to the maintenance of diversity in divergent forms with either life history. We also test the utility of our markers in assigning illegally harvested individuals to populations of origin. We found reduced genetic diversity in paedomorphic compared with some, but not all, metamorphic populations. Populations of both forms showed genetic signatures of bottlenecks, underscoring that factors other than paedomorphosis contribute to historical reductions in population size. In general, Ambystoma populations have low interpopulation gene flow and admixture, but paedomorphic populations have higher within‐population relatedness than most metamorphic populations. We discuss historical and current landscape attributes that impact populations and their connectivity, the implications of our findings for ongoing captive propagation programs and the prospects for continued genetic health of Ambystoma in México.
Genetic population structure in the boky‐boky (Carnivora: Eupleridae), a conservation flagship species in the dry deciduous forests of central western Madagascar
Authors: van Vuuren B. Jansen , Woolaver L. , Goodman S. M.
Published: October 2011

The boky‐boky, Mungotictis decemlineata, is an endemic and presumed forest‐dependent carnivoran species restricted to lowland central western Madagascar. It inhabits dry deciduous forests, which have been severely reduced in surface area with ∼60% destroyed or degraded by humans during the past 60 years. M. decemlineata is limited to the remnant forests of the central and southern Menabe, and using samples collected from sites across this zone, a phylogeographic study was conducted based on two mitochondrial (1140 base pairs [bp] of cytochrome b and 563 bp of the control region) and one nuclear fragment (591 bp of the seventh intron of the fibrinogen gene). Forty‐seven individuals were included from the central Menabe from four principal localities and two animals from the southern Menabe from a single locality. Low sequence divergence (1.65% for the combined fragment, 4.26% for the control region and 0.78% for cytochrome b) characterized specimens across a zone of 130 km delimited by the Tsiribihina River to the north and the Mangoky River to the south; this area includes most of the geographical range of M. decemlineata. Phylogenetic trees, haplotype networks and exact test of population differentiation did not reveal any meaningful geographic partitioning of genetic variation. However, shallow yet significant genetic structure was revealed by ΦST calculations for the combined as well as separate DNA fragments, which we ascribe to isolation‐by‐distance. We proposed two different scenarios to explain the lack of meaningful phylogeographical structure in Mungotictis: (1) for this forest‐dependent species, dispersal during periods of more continuous forest cover gave rise to a genetic meta‐population or (2) that it is able to cross non‐forested zones and broadly disperses, leading to high levels of genetic homogeneity. Current inferences favour the first hypothesis. The short‐ and medium‐term future of this taxon is in jeopardy associated with habitat destruction across its geographical range.
An analysis of the interrelationship between maternal age, body mass index and racial origin in the development of gestational diabetes mellitus
Authors: Makgoba M , Savvidou MD , Steer PJ
Published: October 2011

Please cite this paper as: Makgoba M, Savvidou M, Steer P. An analysis of the interrelationship between maternal age, body mass index and racial origin in the development of gestational diabetes mellitus. BJOG 2011; DOI: 10.1111/j.1471‐0528.2011.03156.x.

Objective  To examine the individual association between advancing maternal age, body mass index (BMI) and racial origin with the development of gestational diabetes mellitus (GDM) and the interaction between these factors.

Design  Retrospective study.

Setting  Fifteen maternity units in northwest London between 1988 and 2000.

Population  The study included 1688 women who developed GDM and 172 632 who did not. All women were nulliparous. BMI was calculated at first antenatal visit and maternal age and racial origin (White European, Black African, Black Caribbean or South Asian) were self‐reported.

Methods  Binary logistic regression analysis.

Main outcome measures  Development of GDM within each racial group.

Results  There was a strong positive association between advancing maternal age and increasing BMI, individually, and the development of GDM (P < 0.01 for both). Compared with White Europeans aged 20–24 years, the odds ratios for GDM development were significantly higher in women older than 30 years if they were White Europeans (P < 0.001), older than 25 years if they were Black Africans (P < 0.001) and older than 20 years if they were South Asians (P < 0.001). The odds ratios for GDM development were significantly higher in Black Africans and South Asians (P < 0.001 for both) irrespective of BMI, compared with White Europeans with normal BMI.

Conclusion  Maternal age and BMI interact with racial group in relation to the prevalence of GDM. Both factors are important in the development of GDM, particularly so in Black African and South Asian women.
Brain‐derived neurotrophic factor uses CREB and Egr3 to regulate NMDA receptor levels in cortical neurons
Authors: Kim Julia H. , Roberts Daniel S. , Hu Yinghui , Lau Garrick C. , Brooks‐Kayal Amy R. , Farb David H. , Russek Shelley J.
Published: October 2011

J. Neurochem. (2012) 120, 210–219.

Regulation of gene expression via brain‐derived neurotrophic factor (BDNF) is critical to the development of the nervous system and may well underlie cognitive performance throughout life. We now describe a mechanism by which BDNF can exert its effects on postsynaptic receptor populations that may have relevance to both the normal and diseased brain where BDNF levels either rise or fall in association with changes in excitatory neurotransmission. Increased levels of NMDA receptors (NMDARs) occur in rat cortical neurons via synthesis of new NMDA receptor 1 (NR1) subunits. The majority of synthesis is controlled by binding of cAMP response element binding protein (CREB) and early growth response factor 3 (Egr3) to the core NR1 promoter (NR1‐p) region. BDNF‐mediated NR1 transcription depends upon induction of the mitogen‐activated protein kinase (MAPK) pathway through activation of the TrK‐B receptor. Taken together with the fact that NMDAR activation stimulates BDNF synthesis, our results uncover a feed‐forward gene regulatory network that may enhance excitatory neurotransmission to change neuronal behavior over time.
Acute administration of fluoxetine normalizes rapid eye movement sleep abnormality, but not depressive behaviors in olfactory bulbectomized rats
Authors: Wang Yi‐Qun , Tu Zhi‐Cai , Xu Xing‐Yuan , Li Rui , Qu Wei‐Min , Urade Yoshihiro , Huang Zhi‐Li
Published: October 2011

J. Neurochem. (2012) 120, 314–324.

In humans, depression is associated with altered rapid eye movement (REM) sleep. However, the exact nature of the relationship between depressive behaviors and sleep abnormalities is debated. In this study, bilateral olfactory bulbectomy (OBX) was carried out to create a model of depression in rats. The sleep–wake profiles were assayed using a cutting‐edge sleep bioassay system, and depressive behaviors were evaluated by open field and forced swimming tests. The monoamine content and monoamine metabolite levels in the brain were determined by a HPLC‐electrochemical detection system. OBX rats exhibited a significant increase in REM sleep, especially between 15:00 and 18:00 hours during the light period. Acute treatment with fluoxetine (10 mg/kg, i.p.) immediately abolished the OBX‐induced increase in REM sleep, but hyperactivity in the open field test and the time spent immobile in the forced swimming test remained unchanged. Neurochemistry studies revealed that acute administration of fluoxetine increased serotonin (5‐HT) levels in the hippocampus, thalamus, and midbrain and decreased levels of the 5‐HT metabolite 5‐hydroxyindoleacetic acid (5‐HIAA). The ratio of 5‐HIAA to 5‐HT decreased in almost all regions of the brain. These results indicate that acute administration of fluoxetine can reduce the increase in REM sleep but does not change the depressive behaviors in OBX rats, suggesting that there was no causality between REM sleep abnormalities and depressive behaviors in OBX rats.
D2‐Dopamine receptors target regulator of G protein signaling 9‐2 to detergent‐resistant membrane fractions
Authors: Celver Jeremy , Sharma Meenakshi , Kovoor Abraham
Published: October 2011

J. Neurochem. (2012) 120, 56–69.

Detergent‐resistant membranes (DRM) are thought to contain structures such as lipid rafts that are involved in compartmentalizing cell membranes. We report that the majority of D2‐dopamine receptors (D2R) expressed endogenously in mouse striatum or expressed in immortalized cell‐lines is found in DRM. In addition, exogenous co‐expression of D2R in a cell line shifted the expression of regulator of G protein signaling 9‐2 (RGS9‐2) into DRM. RGS9‐2 is a protein that is highly enriched in the striatum and specifically regulates striatal D2R. In the striatum, RGS9‐2 is mostly associated with DRMs but when expressed in cell lines, RGS9‐2 is present in the soluble cytoplasmic fraction. In contrast, the majority of mu opioid receptors and delta opioid receptors are found in detergent‐soluble membrane and there was no shift of RGS9‐2 into DRM after co‐expression of mu opioid receptor. These data suggest that the targeting of RGS9‐2 to DRM in the striatum is mediated by D2R and that DRM is involved in the formation of a D2R signaling complex. D2R‐mediated targeting of RGS9‐2 to DRM was blocked by the deletion of the RGS9‐2 DEP domain or by a point mutation that abolishes the GTPase accelerating protein function of RGS9‐2.
Intraportal administration of DPP‐IV inhibitor regulates insulin secretion and food intake mediated by the hepatic vagal afferent nerve in rats
Authors: Fujiwara Kansuke , Gotoh Koro , Chiba Seiichi , Masaki Takayuki , Katsuragi Isao , Kakuma Tetsuya , Yoshimatsu Hironobu
Published: October 2011

J. Neurochem. (2012) 121, 66–76.

Glucagon‐like peptide‐1 (GLP‐1) stimulates insulin secretion and suppresses food intake. Recent studies indicate that the hepatic vagal afferent nerve is involved in this response. Dipeptidyl peptidase‐IV (DPP‐IV) inhibitor extends the half‐life of endogenous GLP‐1 by preventing its degradation. This study aimed to determine whether DPP‐IV inhibitor‐induced elevation of portal GLP‐1 levels affect insulin secretion and feeding behavior via the vagal afferent nerve and hypothalamus. The effect of DPP‐IV inhibitor infusion into the portal vein or peritoneum on portal and peripheral GLP‐1 levels, food intake, and plasma insulin and glucose was examined in sham‐operated and vagotomized male Sprague–Dawley rats. Analyses of neuronal histamine turnover and immunohistochemistry were used to identify the CNS pathway that mediated the response. Intraportal administration of the DPP‐IV inhibitor significantly increased portal (but not peripheral) GLP‐1 levels, increased insulin levels, and decreased glucose levels. The DPP‐IV inhibitor suppressed 1‐ and 12‐ but not 24‐h cumulative food intake. Intraportal infusion of the DPP‐IV inhibitor increased hypothalamic neuronal histamine turnover and increased c‐fos expression in several areas of the brain. These responses were blocked by vagotomy. Our results indicate that DPP‐IV inhibitor‐induced changes in portal but not systemic GLP‐1 levels affect insulin secretion and food intake. Furthermore, our findings suggest that a neuronal pathway that includes the hepatic vagal afferent nerve and hypothalamic neuronal histamine plays an important role in the pharmacological actions of DPP‐IV inhibitor.
Control of neurite outgrowth by RhoA inactivation
Authors: Jeon Chan‐Young , Moon Mi‐Young , Kim Jong‐Hyun , Kim Hee‐Jun , Kim Jae‐Gyu , Li Yi , Jin Jae‐Kwang , Kim Pyeung‐Hyeun , Kim Hyoung‐Chun , Meier Kathryn E. , Kim Yong‐Sun , Park Jae‐Bong
Published: October 2011

J. Neurochem.(2012)120, 684–698.

cAMP induces neurite outgrowth in the rat pheochromocytoma cell line 12 (PC12). In particular, di‐butyric cAMP (db‐cAMP) induces a greater number of primary processes with shorter length than the number induced by nerve growth factor (NGF). db‐cAMP up‐ and down‐regulates GTP‐RhoA levels in PC12 cells in a time‐dependent manner. Tat‐C3 toxin stimulates neurite outgrowth, whereas lysophosphatidic acid (LPA) and constitutively active (CA)‐RhoA reduce neurite outgrowth, suggesting that RhoA inactivation is essential for the neurite outgrowth from PC12 cells stimulated by cAMP. In this study, the mechanism by which RhoA is inactivated in response to cAMP was examined. db‐cAMP induces phosphorylation of RhoA and augments the binding of RhoA with Rho guanine nucleotide dissociation inhibitor (GDI). Moreover, RhoA (S188D) mimicking phosphorylated RhoA induces greater neurite outgrowth than RhoA (S188A) mimicking dephosphorylated form does. Additionally, db‐cAMP increases GTP‐Rap1 levels, and dominant negative (DN)‐Rap1 and DN‐Rap‐dependent RhoGAP (ARAP3) block neurite outgrowth induced by db‐cAMP. DN‐p190RhoGAP and the Src inhibitor PP2 suppress neurite outgrowth, whereas transfection of c‐Src and p190RhoGAP cDNAs synergistically stimulate neurite outgrowth. Taken together, RhoA is inactivated by phosphorylation of itself, by p190RhoGAP which is activated by Src, and by ARAP3 which is activated by Rap1 during neurite outgrowth from PC12 cells in response to db‐cAMP.