bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell cycle‐dependent formation of Cdc45–Claspin complexes in human cells is compromized by UV‐mediated DNA damage
Authors: Broderick Ronan , Rainey Michael D. , Santocanale Corrado , Nasheuer Heinz P.
Published: August 2013

The replication factor Cdc45 has essential functions in the initiation and elongation steps of eukaryotic DNA replication and plays an important role in the intra‐S‐phase checkpoint. Its interactions with other replication proteins during the cell cycle and after intra‐S‐phase checkpoint activation are only partially characterized. In the present study, we show that the C terminal part of Cdc45 may mediate its interactions with Claspin. The interactions of human Cdc45 with the three replication factors Claspin, replication protein A and DNA polymerase δ are maximal during the S phase. Following UVC‐induced DNA damage, Cdc45–Claspin complex formation is reduced, whereas the binding of Cdc45 to replication protein A is not affected. We also show that treatment of cells with UCN‐01 and phosphatidylinositol 3‐kinase‐like kinase inhibitors does not rescue the UV‐induced destabilization of Cdc45–Claspin interactions, suggesting that the loss of the interaction between Cdc45 and Claspin occurs upstream of ataxia telangiectasia and Rad 3‐related activation in the intra‐S‐phase checkpoint.

Structured digital abstract

Clapsin physically interacts with Cdc45 by anti bait coimmunoprecipitation (View interaction)

Cdc45 physically interacts with RPA32, Clapsin and p125 Pol delta by pull down (View interaction)

Cdc45 physically interacts with RPA32 by pull down (View interaction)

Cdc45 physically interacts with Clapsin by pull down (View interaction)

Cdc45 physically interacts with Clapsin and RPA32 by pull down (View interaction)

RPA32 physically interacts with Cdc45 by anti bait coimmunoprecipitation (View interaction)
Mutations of the domain forming the dimeric interface of the ArdA protein affect dimerization and antimodification activity but not antirestriction activity
Authors: Roberts Gareth A. , Chen Kai , Bower Edward K. M. , Madrzak Julia , Woods Arcadia , Barker Amy M. , Cooper Laurie P. , White John H. , Blakely Garry W. , Manfield Iain , Dryden David T. F.
Published: August 2013

ArdA antirestriction proteins are encoded by genes present in many conjugative plasmids and transposons within bacterial genomes. Antirestriction is the ability to prevent cleavage of foreign incoming DNA by restriction‐modification (RM) systems. Antimodification, the ability to inhibit modification by the RM system, can also be observed with some antirestriction proteins. As these mobile genetic elements can transfer antibiotic resistance genes, the ArdA proteins assist their spread. The consequence of antirestriction is therefore the enhanced dissemination of mobile genetic elements. ArdA proteins cause antirestriction by mimicking the DNA structure bound by Type I RM enzymes. The crystal structure of ArdA showed it to be a dimeric protein with a highly elongated curved cylindrical shape [McMahon SA et al. (2009) Nucleic Acids Res 37, 4887–4897]. Each monomer has three domains covered with negatively charged side chains and a very small interface with the other monomer. We investigated the role of the domain forming the dimer interface for ArdA activity via site‐directed mutagenesis. The antirestriction activity of ArdA was maintained when up to seven mutations per monomer were made or the interface was disrupted such that the protein could only exist as a monomer. The antimodification activity of ArdA was lost upon mutation of this domain. The ability of the monomeric form of ArdA to function in antirestriction suggests, first, that it can bind independently to the restriction subunit or the modification subunits of the RM enzyme, and second, that the many ArdA homologues with long amino acid extensions, present in sequence databases, may be active in antirestriction.

Structured digital abstract

ArdA and ArdA bind by molecular sieving (1, 2)

ArdA and ArdA bind by cosedimentation in solution (1, 2)
Uth1 is a mitochondrial inner membrane protein dispensable for post‐log‐phase and rapamycin‐induced mitophagy
Authors: Welter Evelyn , Montino Marco , Reinhold Robert , Schlotterhose Petra , Krick Roswitha , Dudek Jan , Rehling Peter , Thumm Michael
Published: August 2013

Mitochondria are turned over by an autophagic process termed mitophagy. This process is considered to remove damaged, superfluous and aged organelles. However, little is known about how defective organelles are recognized, what types of damage induce turnover, and whether an identical set of factors contributes to degradation under different conditions. Here we systematically compared the mitophagy rate and requirement for mitophagy‐specific proteins during post‐log‐phase and rapamycin‐induced mitophagy. To specifically assess mitophagy of damaged mitochondria, we analyzed cells accumulating proteins prone to degradation due to lack of the mitochondrial AAA‐protease Yme1. While autophagy 32 (Atg32) was required under all tested conditions, the function of Atg33 could be partially bypassed in post‐log‐phase and rapamycin‐induced mitophagy. Unexpectedly, we found that Uth1 was dispensable for mitophagy. A re‐evaluation of its mitochondrial localization revealed that Uth1 is a protein of the inner mitochondrial membrane that is targeted by a cleavable N‐terminal pre‐sequence. In agreement with our functional analyses, this finding excludes a role of Uth1 as a mitochondrial surface receptor.
The Nature of Gentrification
Authors: Bryson Jeremy
Published: August 2013

Gentrification research provides many important insights into the transformation of contemporary urban landscapes, yet more careful attention to nature's role in this process is necessary. This essay begins by highlighting how gentrification research has traditionally overlooked the environmental factors of gentrification and continues by showing how researchers are beginning to account for the urban natural environment in gentrification processes. Such an environmentally sensitive approach to gentrification—one that accounts for nature being used by powerful groups as a tool of social power but also leaves room for it to be a dynamic material actor—can aid scholars' understanding of this important urban process.
Rebuke: From Trope to Event in Paul Celan's “Zähle die Mandeln”
Authors: Tucker Brian
Published: August 2013

“Zähle die Mandeln” has often been interpreted as a metaphorical encoding of European history or of Celan's biography. In this paper, I propose, however, that the poem be read with an eye toward linguistic enactment, toward what the words do in addition to what they say. When one reads in this way, one finds that the poem itself calls into question a metaphorical mode of interpretation. “Zähle die Mandeln” embodies the tension between representation and performance and stages, within language, a passage from trope to event. I ultimately argue that the poem's willful suspension of image and reference, far from denying history, enacts its more radical engagement with history.
GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation
Authors: Suzuki Mikiko , Kobayashi‐Osaki Maki , Tsutsumi Shuichi , Pan Xiaoqing , Ohmori Shin'ya , Takai Jun , Moriguchi Takashi , Ohneda Osamu , Ohneda Kinuko , Shimizu Ritsuko , Kanki Yasuharu , Kodama Tatsuhiko , Aburatani Hiroyuki , Yamamoto Masayuki
Published: August 2013

Transcription factor GATA2 is highly expressed in hematopoietic stem cells and progenitors, whereas its expression declines after erythroid commitment of progenitors. In contrast, the start of GATA1 expression coincides with the erythroid commitment and increases along with the erythroid differentiation. We refer this dynamic transition of GATA factor expression to as the ‘GATA factor switching’. Here, we examined contribution of the GATA factor switching to the erythroid differentiation. In Gata1‐knockdown embryos that concomitantly express Gata2‐GFP reporter, high‐level expression of GFP reporter was detected in accumulated immature hematopoietic cells with impaired differentiation, demonstrating that GATA1 represses Gata2 gene expression in hematopoietic progenitors in vivo. We have conducted chromatin immunoprecipitation (ChIP) on microarray analyses of GATA2 and GATA1, and results indicate that the GATA1‐binding sites widely overlap with the sites pre‐occupied by GATA2 before the GATA1 expression. Importantly, erythroid genes harboring GATA boxes bound by both GATA1 and GATA2 tend to be expressed in immature erythroid cells, whereas those harboring GATA boxes to which GATA1 binds highly but GATA2 binds only weakly are important for the mature erythroid cell function. Our results thus support the contention that preceding binding of GATA2 helps the following binding of GATA1 and thereby secures smooth expression of the transient‐phase genes.
Bone density in haemophilia: a single institutional cross‐sectional study
Authors: Kempton C. L. , Antun A. , Antoniucci D. M. , Carpenter W. , Ribeiro M. , Stein S. , Slovensky L. , Elon L.
Published: August 2013

Haemophilia has been associated with low bone mineral density (BMD). However, prior clinical studies of this population have neither clearly elucidated risk factors for development of low BMD nor identified who may warrant screening for osteoporosis. The aim of the study was to evaluate the relationship between BMD and haemophilic arthropathy and other demographic and clinical variables. We undertook a cross‐sectional study of BMD in adult men with haemophilia. Measures of predictor variables were collected by radiographic studies, physical examination, patient questionnaires and review of medical records. Among 88 enrolled subjects, the median age was 41 years (IQR: 20); median femoral neck BMD (n = 87) was 0.90 g cm−2 (IQR: 0.24); and median radiographic joint score was 7.5 (IQR: 18). Among subjects <50 years (n = 62), after controlling for BMI, alcohol, HIV and White race, BMD decreased as radiographic joint score increased (est. β = −0.006 mg cm−2; 95% CI −0.009, −0.003; partial R2 = 0.23). Among subjects ≥50 years (n = 26), 38% had osteoporosis (T score less than or equal to −2.5) and there was no association between BMD and arthropathy. Risk factors for low BMD in men with haemophilia <50 years include haemophilic arthropathy, low or normal BMI and HIV. Men with haemophilia over age 50 years should have routine screening for detection of osteoporosis.
Association of tyrosine with insulin resistance in hepatitis C virus‐related chronic liver disease
Authors: Oono Takashi , Yamasaki Takahiro , Zaitsu Junichi , Saeki Issei , Iwamoto Takuya , Harima Yumiko , Marumoto Yoshio , Hidaka Isao , Urata Yohei , Ishikawa Tsuyoshi , Takami Taro , Segawa Makoto , Uchida Koichi , Terai Shuji , Kunitugu Ichiro , Tanabe Tsuyoshi , Sakaida Isao
Published: August 2013

Aim

Insulin resistance (IR) increases during the early stages of hepatitis C virus (HCV)‐related chronic liver disease and is a sign of poor prognosis as well as a risk factor for hepatic fibrosis and hepatocellular carcinoma. We aimed to determine the factors affecting IR in HCV‐related chronic liver disease.

Methods

We retrospectively examined 71 patients with HCV‐related chronic liver disease and analyzed various parameters, including amino acids, as possible predictors of IR. IR was assessed using the Homeostasis Model of Assessment – Insulin Resistance (HOMA‐IR). Amino acids were assayed by examining branched‐chain amino acids (BCAA), tyrosine level, and the ratio of BCAA to tyrosine level (BTR).

Results

HOMA‐IR was significantly correlated with body mass index, platelet count, prothrombin time, hemoglobin, total bilirubin, total protein, albumin, total cholesterol, fasting glucose, BTR (r = −0.46, P = 0.0001) and tyrosine (r = 0.55, P < 0.0001). However, BCAA were not significantly correlated with HOMA‐IR (r = −0.21, P = 0.082). In multivariate analysis, only two factors were identified as independent parameters contributing to a HOMA‐IR of 2.5 or more: total cholesterol (odds ratio [OR], 6.511; 95% confidence interval [95% CI], 1.554–27.284; P = 0.010) and tyrosine (OR, 4.839; 95% CI, 1.087–21.549; P = 0.039).

Conclusion

Serum tyrosine levels may be associated with IR in patients with HCV‐related chronic liver disease.
Application of deep sequence technology in hepatology
Authors: Ninomiya Masashi , Ueno Yoshiyuki , Shimosegawa Tooru
Published: August 2013

Deep sequencing technologies are currently cutting edge, and are opening fascinating opportunities in biomedicine, producing over 100‐times more data compared to the conventional capillary sequencers based on the Sanger method. Next‐generation sequencing (NGS) is now generally defined as the sequencing technology that, by employing parallel sequencing processes, producing thousands or millions of sequence reads simultaneously. Since the GS20 was released as the first NGS sequencer on the market by 454 Life Sciences, the competition in the development of the new sequencers has become intense. In this review, we describe the current deep sequencing systems and discuss the application of advanced technologies in the field of hepatology.
Patients' perspective on self‐management in the recovery from depression
Authors: van Grieken Roos A. , Kirkenier Anneloes C.E. , Koeter Maarten W.J. , Nabitz Udo W. , Schene Aart H.
Published: August 2013

Background

Self‐management appears to be a promising approach in the case of depression, which helps to stimulate patients' autonomy. However, a good and systematic description of the concept self‐management from the patients' perspective, to our knowledge, has not yet been performed.

Objective

To determine: (i) what strategies patients think they can use themselves to recover from depression, (ii) which main themes of self‐management strategies can be detected, and (iii) which of these strategies patients perceive as being most helpful.

Methods

We used concept mapping to explore the experiences of patients who recently recovered from a depressive episode. Patients generated self‐management strategies in focus group discussions. The strategies were clustered on a two‐dimensional concept map by a hierarchical cluster analysis.

Results

Patients generated 50 strategies that formed eight clusters: (i) proactive attitude towards depression and treatment, (ii) daily life strategies and rules, (iii) explanation of disease to others, (iv) remaining socially engaged, (v) engaging in activities, (vi) structured attention to oneself, (vii) contact with fellow sufferers, and (viii) other. Behavioural and cognitive strategies and a proactive attitude towards treatment were considered as the most helpful.

Discussion and conclusion

From the patients' perspective, there is a wide range of self‐management strategies that they can use – and perceive as helpful‐ to contribute to their own recovery. Professionals could encourage patients to take an active role in achieving recovery. Further research could open new roads to improve patients' active contributions to current treatments for depression.
Presenting life with cystic fibrosis: a Q‐methodological approach to developing balanced, experience‐based prenatal screening information
Authors: Wright Katherine F. , Bryant Louise D. , Morley Stephen , Hewison Jenny , Duff Alistair J.A. , Peckham Daniel
Published: August 2013

Background

Cystic fibrosis (CF) is one of the most common life‐threatening genetically inherited conditions and prenatal screening for CF is available in many countries. Genetic counsellors and other health professionals are expected to provide information about the condition in a way that facilitates personal decision making. Knowing what information to deliver about complex genetic conditions to support informed screening decisions can be challenging for health professionals.

Objective

To solicit views from those with personal experience with CF on which aspects of the condition they consider most important to include in prenatal screening materials.

Methods

Q‐methodology; an approach to systematically explore variations in viewpoint that combines factor analytic techniques with qualitative approaches to pattern interpretation. Setting and Participants: Twelve adults with CF and 18 parents of affected children were recruited from a regional centre in the UK.

Results

Five distinct viewpoints on the items most and least important to include in screening information were identified: Factor 1 the normality of life with CF and increasing life expectancy; Factor 2 the hardships and reduced lifespan. Factor 3 medical interventions and the importance of societal support. Factor 4 longer‐term consequences of CF. Factor 5 the ability to adjust to the condition.

Discussion

The identification of five different views on what represented the most and least important information to include about CF highlights the challenge of portraying a complex genetic condition in a balanced and accurate manner. Novel ways in which Q‐methodology findings can be used to meet this challenge are presented.
Hepatic involvement in paediatric patients with paracoccidioidomycosis: a histological study
Authors: de Melo Braga Giselle , Hessel Gabriel , Pereira Ricardo Mendes , Escanhoela Cecília Amélia Fazzio
Published: August 2013

Aim

Paracoccidioidomycosis is a systemic mycosis that is endemic to certain countries in Latin America. This study aimed to describe the histological features of liver involvement in patients with paracoccidioidomycosis aged <16 years of age who were treated between 1980 and 2010, with a diagnosis that was confirmed by detection of the fungus by pathological examination.

Methods and results

Liver tissue was obtained from one necropsy and 12 biopsies. Throughout 2007, biopsies were taken from patients with persistent jaundice or portal hypertension, after which biopsies became indicated due to elevated aminotransferase and low albumin levels. Using haematoxylin and eosin (H&E), Masson's trichrome and immunohistochemical (CK7 and CK19) staining, we noted degenerative alterations in bile duct cells and inflammatory injury to the bile ducts in 10 biopsies. Using immunohistochemistry for CK7 and CK19, we observed ductal proliferation in all 12 samples.

Conclusions

Bile duct injuries by inflammatory cells might explain the predominant increase in canalicular enzymes; immunohistochemistry is more sensitive in demonstrating ductular reactions and might show changes that are not apparent on H&E staining.
Phylogenetic analyses of vector mosquito basic helix‐loop‐helix transcription factors
Authors: Zhang D. B. , Wang Y. , Liu A. K. , Wang X. H. , Dang C. W. , Yao Q. , Chen K. P.
Published: August 2013

Basic helix‐loop‐helix (bHLH) transcription factors play critical roles in the regulation of a wide range of developmental processes in higher organisms and have been identified in more than 20 organisms. Mosquitoes are important vectors of certain human diseases. In this study, Aedes aegypti, Anopheles gambiae str. PEST and Culex quinquefasciatus genomes were found to encode 55, 55 and 57 bHLH genes, respectively. Further phylogenetic analyses and OrthoDB and Kyoto encyclopedia of genes and genomes orthology database searches led us to define orthology for all the identified mosquito bHLHs successfully. This provides useful information with which to update annotations to 40 Ae. aegypti, 55 An. gambiae and 38 C. quinquefasciatus bHLH genes in VectorBase. The mosquito lineage has more bHLH genes in the Atonal, neurogenin (Ngn) and Hes‐related with YRPW motif (Hey) families than do other insect species, suggesting that mosquitoes have evolved to be more sensitive to vibration, light and chemicals. Mosquito bHLH genes generally have higher evolutionary rates than other insect species. However, no pervasive positive selection occurred in the evolution of insect bHLH genes. Only episodic positive selection was found to affect evolution of bHLH genes in 11 families. Besides, coding regions of several Ae. aegypti bHLH motifs have unusually long introns in which multiple copies of transposable elements have been identified. These data provide a solid basis for further studies on structures and functions of bHLH proteins in the regulation of mosquito development and for prevention and control of mosquito‐mediated human diseases.
A hypervariable pig DNA fragment
Authors: COPPIETERS W. , VAN DE WEGHE A. , DEPICKER A. , BOUQUET Y. , VAN ZEVEREN A.
Published: August 2013

Summary A new hypervariable tandem repeat was isolated from the pig genome and characterized by DNA sequence. The use of this DNA fragment as a probe in order to follow allelic segregation and DNA fingerprinting in pigs, horses and rabbits is documented.
The definition of five B lymphocyte alloantigens closely linked to BoLA class I antigens
Authors: MACKIE J. T. , STEAR M. J.
Published: August 2013

Summary B lymphocyte alloantigens in cattle were identified by serological analysis. Alloantisera were raised by skin implant immunization or leucocyte immunization and were absorbed with platelets to reduce class I‐specific antibody activity. Leucocyte absorptions were done to reduce the complexity of some antisera. A panning technique was used to prepare B‐enriched and B‐depleted lymphocytes. Antisera which displayed anti‐B cell activity over a number of dilutions were tested against 115 Charolais cattle, and 13 antisera were used to define five B lymphocyte alloantigens. These antigens were present on B lymphocytes but did not appear to be present, at least at the same density, on the majority of T lymphocytes or platelets. Family studies suggested that these antigens are coded by one or two loci which are closely linked to the bovine class I loci. These results suggest the five antigens are class II antigens of the major histocompatibility complex (MHC) of cattle.
Genetic variation and distances of five Italian native sheep breeds
Authors: CASATI M. ZANOTTI , GANDINI G. C. , LEONE P.
Published: August 2013

Summary Genetic distances among five of the most important Italian native sheep breeds were estimated by using gene frequencies of four blood group and seven blood protein loci and by three different computing methods. The values of the three distance matrices were highly correlated. Genetic distances were found within the range values reported in the literature for local breeds. Shorter distances fitted the historical evidence of migrations.
Equus przewalskii plasma protease inhibitor (Pi) system
Authors: PATTERSON S. D. , BELL K. , MANTON V. J. A.
Published: August 2013

Summary A detailed biochemical characterization of four of the five previously described alleles of the plasma protease inhibitor (Pi) system of Equus przewalskii was performed using both one‐ and two‐dimensional electrophoretic techniques. The proteins have been characterized in terms of isoelectric point, relative molecular mass, inhibitory activity to bovine trypsin and chymotrypsin, immunochemical cross‐reactivity, terminal sialic acid content and enzyme:inhibitor complex formation and the oxidation sensitivity of this interaction. Using these functional criteria, only three loci (Spi 1,2 and 3) were found to control the plasma Pi proteins of the E. przewalskii haplotypes. In contrast a fourth locus, Spi 4, was found in some E. caballus haplotypes. The significance of these results with respect to the complexity of the protein pattern exhibited by the equine Pi multigene family is discussed.
Identification of goat allotypic determinants and generation of goat‐mouse hybridomas secreting goat IgG2
Authors: CAPPARELLI R. , DEL SORBO G. , IANNELLI D.
Published: August 2013

Summary Five allotypic determinants controlled by independent genes have been identified in goat. Of these determinants, four have been detected with alloimmune antisera and one with monoclonal antibodies. The specificities A1, C1 and D1 are lipoproteins; B1 is possibly an α2 macroglobulin and E1 an IgG2. The specificity B1 is not expressed until the age of 3–4 months. The gene controlling the specificity E1 is present at about the same frequency (0·38‐0·41) in goat, sheep, cattle and water buffalo. Stable hybridomas secreting goat IgG2 have been obtained by the fusion of goat peripheral lymphocytes with mouse myeloma cells.
Extensive polymorphism at adenosine deaminase in the marine fishSciaenops ocellatus(L.)
Authors: BOHLMEYER D. A. , GOLD J. R.
Published: August 2013

SummaryEleven different allelic variants at the adenosine deaminase (ADA) locus have been detected using vertical starch‐gel electrophoresis among 474 individuals of the marine fishSciaenops ocellatus(L.). Thirty‐five of the 66 possible genotypes were observed, and the heterozygosity level at ADA was estimated to be 70·3%. The extensive polymorphism at ADA may prove useful in terms of providing genetic markers for stocking programs using hatchery‐raised fish.
Genetic systems of red cell blood groups in goats
Authors: NGUYEN T. C.
Published: August 2013

Summary Evidence is presented for six genetic systems of goat red cell blood groups. The A system presently consists of one specificity, two alleles, two phenotypes (A1 and no‐A1) and appears to be homologous to the A system of sheep. The B system, like its homologue in sheep, is very complex. Fourteen of 21 specificities detected in the present study, i.e. B2, B3, B4, B5, B7, B8, B9, B10, B11, B14, B15, B16, B17 and B20, belong to the B system which involves a large number of phenogroups (31 different B phenogroups identified in 26 sires).

Because of their homology with sheep C and R systems, two other genetic systems of goat blood groups are named C and R respectively. Each of the two goat systems is presently a one blood group specificity, two phenotype (C12 and no‐C12; R and no‐R detectable on the red cells) two allele system.

Two specificities, namely E6 and E18, belong to a genetic system called E in which four phenotypes are under the control of two alleles codominant and one recessive at a single locus.

The F system involves but a single pair of alleles and two phenotypes (F19 and no‐F19).

Because of its low frequency in the goats tested, the X13 specificity remains unassigned.
Transferrin and albumin polymorphisms in buffaloes from Brazil
Authors: SCHNEIDER H. , SCHNEIDER M. P. C. , DA SILVA B. T. F. , SALZANO F. M.
Published: August 2013

Summary Starch gel electrophoresis disclosed six transferrin phenotypes, explainable by three alleles (TF A, TF D, TF E), and three albumin phenotypes, determined by two alleles (ALB A, ALB B). Their prevalences suggest that the Brazilian populations have admixed river and swamp buffalo ancestry, the frequency of ALB A being much higher than those found in other regions.
Coping strategies and first year performance in postsecondary education
Authors: Alarcon Gene M. , Edwards Jean M. , Clark Patrick C.
Published: August 2013

Coping was hypothesized to explain additional variance in first year grade point averages (GPAs) controlling for cognitive ability and conscientiousness. First year GPAs were assessed as criterion for performance in the first year. Results indicate active coping, denial, behavioral disengagement, and alcohol disengagement are related to first year GPA. Denial and alcohol disengagement coping strategies were significant predictors and negatively related to first year GPA in the final regression equation controlling for cognitive ability and conscientiousness. Latent growth modeling analysis demonstrated cognitive ability predicted both the intercept and slope of first year GPA. Conscientiousness was a predictor of initial GPA but not change. Lastly, coping was a significant predictor of change in GPA. Implications for research and theory are discussed.
Outflow Tract Ventricular Tachycardia Mapped to the Coronary Arteries: Anatomical Correlates and Management Strategies
Authors: VAIDYA VAIBHAV , SYED FAISAL , DESIMONE CHRISTOPHER , BDEIR SAMI , MUNOZ FREDDY DEL CARPIO , PACKER DOUGLAS L. , ASIRVATHAM SAMUEL J.
Published: August 2013

Coronary Artery Ventricular Tachycardia. Background

The coronary cusps have been well described as a successful site for ablation in patients with symptomatic outflow tract ventricular tachycardia. The earliest site of activation is rarely found at the ostia or into the main coronary arteries. The exact anatomic substrate, diagnostic characteristics, and therapeutic approaches for such instances are poorly understood.

Methods

We retrospectively reviewed outflow tract ventricular arrhythmia (OTVA) ablations done at Mayo Clinic Rochester from 2003 to 2011 (total VT: 414; outflow tract VT: 106). Three cases were identified where the earliest site of activation was not within the cusp but rather at or within the coronary ostia (3/414 for all VT: 0.7%; 3/106 for all OTVT: 2.8%).

Results

In 1 patient, the left main coronary artery (LMCA) was found to have electrograms (EGMs) recorded with bipolar mapping that preceded activation in the cusps or the left ventricular outflow tract. In 2 cases, the right coronary ostium and proximal right coronary artery recorded the earliest signals. Intracardiac echocardiographic guidance was used to successfully ablate these arrhythmias targeting the aortic route (1 patient) or the right coronary cusp (2 patients), and essentially isolated the focus of origin from the ventricular outflow tracts. Detailed mapping of surrounding structures, including the atrial appendages, the contralateral outflow tract, and the coronary venous system excluded far‐field mapping in the artery as a cause for early activation at the ostial location. Local EGM characteristics suggested an unusually lengthy supravalvar myocardial extension as the likely arrhythmogenic substrate. Ablation was successful without coronary arterial or valvular injury and without valvular or root stenosis.

Conclusions

Endocardial ablation isolating foci of origin in the vicinity of the coronary ostia is a challenging procedure but can be performed safely with appropriate visualization and is effective in the treatment of OTVA.
Efficacy of Catheter Ablation in Nonparoxysmal Atrial Fibrillation Patients with Severe Enlarged Left Atrium and Its Impact on Left Atrial Structural Remodeling
Authors: PUMP AGNES , DI BIASE LUIGI , PRICE JUSTIN , MOHANTY PRASANT , BAI RONG , SANTANGELI PASQUALE , MOHANTY SANGHAMITRA , TRIVEDI CHINTAN , YAN RACHEL (XUE) , HORTON RODNEY , SANCHEZ JAVIER E. , ZAGRODZKY JASON , BAILEY SHANE , GALLINGHOUSE G. JOSEPH , BURKHARDT J. DAVID , NATALE ANDREA
Published: August 2013

AF Ablation in Patients with Large LA

Introduction

The effect of catheter ablation on severe left atrial enlargement especially in nonparoxysmal atrial fibrillation (NPAF) patients is not well understood. Whether reverse remodelling may occur after ablation has not been evaluated in this setting.

Methods and results

Fifty consecutive patients with left atrial diameter (LAD) ≥50 mm, and LA volume >200 cc undergoing catheter ablation for drug‐refractory NPAF were included in this study. Transthoracic echocardiographic measurements were performed at baseline and at 12‐months postprocedure. Left ventricular end‐diastolic and end‐systolic dimensions were indexed by body surface area (LVEDDI, LVESDI). Electroanatomic mapping system (Carto or NavX system) and computed tomography (CT) were used for 3‐dimensional reconstruction of the LA. All patients underwent posterior wall isolation and pulmonary vein (PV) antrum and extra PV trigger ablations. Long‐term follow‐up was monitored by event recordings, 7‐day Holter monitors and office visits.

The mean age was 65 ± 10 years, 78% male, persistent AF 22 (44%), longstanding AF 28 (56%), LAD diameter 56.9 ± 7.8 mm, left ventricular ejection fraction (LVEF) 53 ± 14 and median AF duration 72 (49–96) months. At 12‐month follow‐up, 27 patients (54%) remained arrhythmia‐free off antiarrhythmic drugs. Significant reduction in LAD at follow‐up (≥10% reduction) was observed in 52% (26/50) of the total population and among the 63% (17/27) of recurrence‐free patients. Magnitude of LA reduction was identically distributed among the persistent and longstanding persistent AF cohorts (16 ± 12% vs 14 ± 16%, respectively, P = 0.15). A significant 20% improvement in LVEF (from 53 ± 14 to 58 ± 9, P = 0.03) was found in the overall population. Improvement was noted in recurrence‐free patients. No significant change in LVEDDI and LVESDI was noted. After adjusting for baseline risk factors in a multivariable model, a reduction in LAD was identified as a strong predictor of long‐term success (beta = –11.1, P = 0.013). Preexisting LA scarring was associated with increased LAD (beta = 2.7, P = 0.023). No periprocedural or long‐term complications were reported.

Conclusion

Our results show that atrial fibrillation ablation is effective in NPAF patients with severe LA enlargement and is associated with LA reverse remodeling and improvement in LVEF.
Effects of Cystamine on antioxidant activities and regulatory T cells in lupus‐prone mice
Authors: Hsu Tsai‐Ching , Chiu Chun‐Ching , Wang Yi‐Wen , Tzang Bor‐Show
Published: August 2013

Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well‐established beneficial effects of cystamine on lupus‐prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti‐oxidant activities in NZB/W F1 mice by performing assays of Glutathione (GSH), 1,1‐diphenyl‐2‐ picryl‐hydrazyl (DPPH) and malondialdehyde thiobarbituric acid (MDA). In addition, investigations of the effects of cystamine on CD4+/CD25+ regulatory T cells and interleukin‐6 (IL6)/STAT‐3 signalling were performed with flow cytometry and immunoblots. Experimental results reveal more significantly reduced MDA and increased GSH and DPPH in NZB/W F1 mice receiving cystamine than in those mice receiving PBS. Meanwhile, CD4+/CD25+ regulatory T cells more significantly increase in NZB/W F1 mice receiving cystamine than in those mice receiving PBS, accompanied by significantly reduced IL‐6/phosphorylated STAT‐3 expression. The above findings suggest the beneficial effects of cystamine in terms of increasing antioxidant activities and CD4+/CD25+ regulatory T cells in lupus‐prone mice by suppressing IL‐6/STAT3 signalling.
Circulating plasma serine208‐phosphorylated troponin T levels are indicator of cardiac dysfunction
Authors: Dubois‐Deruy Emilie , Belliard Aude , Mulder Paul , Chwastyniak Maggy , Beseme Olivia , Henry Jean‐Paul , Thuillez Christian , Amouyel Philippe , Richard Vincent , Pinet Florence
Published: August 2013

Heart failure (HF) following myocardial infarction (MI) is characterized by progressive alterations of left ventricular (LV) structure and function, named LV remodelling. Although several risk factors such as infarct size have been identified, HF remains difficult to predict in clinical practice. Recently, using phosphoproteomic technology, we found that serine208‐phosphorylated troponin T (P‐Ser208‐TnT) decreases in LV of HF rats. Our aim was to determine the performance of P‐Ser208‐TnT as plasma biomarker of HF compared to conventional cardiac biomarkers such as B‐type natriuretic peptide (BNP), cardiac troponin I (cTnI), C‐reactive protein (CRP) or tissue inhibitor of metalloproteinase I (TIMP‐1) measured by x‐MAP technology, as well as its capacity to reflect a pharmacological improvement of HF. We observed a significant increase of BNP, TnT and cTnI levels and a significant decrease of P‐Ser208‐TnT and TIMP‐1 in the plasma of 2‐month‐MI rats compared with control rats with no modulation of CRP level. Circulating levels of P‐Ser208‐TnT were shown to be associated with most of the echocardiographic and haemodynamic parameters of cardiac function. We verified that the decrease of P‐Ser208‐TnT was not because of an excess of phosphatase activity in plasma of HF rats. Two‐month‐MI rats treated with the heart rate reducing agent ivabradine had improved LV function and increased plasma levels of P‐Ser208‐TnT. Thus, circulating phosphorylated troponin T is a highly sensitive biological indicator of cardiac dysfunction and has the potentiality of a new biomarker of HF post‐MI, and of a surrogate marker for the efficacy of a successful treatment of HF.
Gene × smoking interactions on human brain gene expression: finding common mechanisms in adolescents and adults
Authors: Wolock Samuel L. , Yates Andrew , Petrill Stephen A. , Bohland Jason W. , Blair Clancy , Li Ning , Machiraju Raghu , Huang Kun , Bartlett Christopher W.
Published: August 2013

Background

Numerous studies have examined gene × environment interactions (G × E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G × E interactions using two publically available datasets to assess if DNA variation is associated with post‐mortem brain gene expression changes based on smoking behavior, a biobehavioral construct that is part of a complex system of genetic and environmental influences.

Methods

We conducted an expression quantitative trait locus (eQTL) study on two independent human brain gene expression datasets assessing G × E for selected psychiatric genes and smoking status. We employed linear regression to model the significance of the Gene × Smoking interaction term, followed by meta‐analysis across datasets.

Results

Overall, we observed that the effect of DNA variation on gene expression is moderated by smoking status. Expression of 16 genes was significantly associated with single nucleotide polymorphisms that demonstrated G × E effects. The strongest finding (p = 1.9 × 10−11) was neurexin 3‐alpha (NRXN3), a synaptic cell–cell adhesion molecule involved in maintenance of neural connections (such as the maintenance of smoking behavior). Other significant G × E associations include four glutamate genes.

Conclusions

This is one of the first studies to demonstrate G × E effects within the human brain. In particular, this study implicated NRXN3 in the maintenance of smoking. The effect of smoking on NRXN3 expression and downstream behavior is different based upon SNP genotype, indicating that DNA profiles based on SNPs could be useful in understanding the effects of smoking behaviors. These results suggest that better measurement of psychiatric conditions, and the environment in post‐mortem brain studies may yield an important avenue for understanding the biological mechanisms of G × E interactions in psychiatry.
Parental social anxiety disorder prospectively predicts toddlers' fear/avoidance in a social referencing paradigm
Authors: Aktar Evin , Majdandžić Mirjana , de Vente Wieke , Bögels Susan M.
Published: August 2013

Background

Anxiety runs in families. Observational learning of anxious behavior from parents with anxiety disorders plays an important role in the intergenerational transmission of anxiety. We investigated the link between parental anxiety (parental lifetime anxiety disorders and expressed parental anxiety) and toddler fear/avoidance during social referencing (SR) situations.

Method

Toddlers (N = 117) participated with both parents (with lifetime social anxiety disorder, other nonsocial anxiety disorders, lifetime comorbid social and other anxiety disorders, or without anxiety disorders) in a longitudinal study. Behavioral inhibition (BI) was measured at 12 months via observational tasks. At 30 months, children were confronted with a stranger and a remote‐control robot in SR situations, separately with each parent. Children's fear and avoidance, and parents' expressions of anxiety, encouragement, and overcontrol were observed.

Results

Toddlers of parents with lifetime social anxiety disorder (alone and comorbid with other anxiety disorders) showed more fear/avoidance in SR situations than toddlers of parents without anxiety disorders, while the effect of other anxiety disorders alone was not significant. Although expressed parental anxiety at 30 months in SR situations did not significantly predict toddlers' fear/avoidance, higher levels of expressed anxiety at 12 months in SR situations by parents with comorbid social and other anxiety disorders predicted higher levels of fear/avoidance. BI at 12 months predicted toddlers' fear/avoidance only with mothers, but not with fathers.

Conclusions

Parental lifetime social anxiety disorders may be a stronger predictor of children's fear/avoidance than parents' expressions of anxiety in SR situations in toddlerhood. End of infancy may be a sensitive time for learning of anxiety from parents with comorbid lifetime social and nonsocial anxiety disorders in SR situations. Fathers are as important as mothers in the transmission of anxiety via SR. Furthermore, children may act relatively free of their early temperament in SR situations with fathers.
Therapeutic efficacy of long‐pulsed 755‐nm alexandrite laser for seborrheic keratoses
Authors: Kim Y.K. , Kim D.‐Y. , Lee S.J. , Chung W.S. , Cho S.B.
Published: August 2013

Background

Both ablative and non‐ablative laser devices have been used for the cosmetic treatment of seborrheic keratoses.

Objectives

We analysed treatment outcomes and adverse events in the treatment of seborrheic keratoses using a long‐pulsed 755‐nm alexandrite laser without colour enhancement.

Methods

A total of 216 seborrheic keratoses in 13 patients were treated with one or three sessions of long‐pulsed 755‐nm alexandrite laser at 1‐month intervals. The lesions were treated with settings of 35 J/cm2 using a 6‐mm spot size, a 3‐ms pulse width, and 1‐2 passes or until the appearance of fine bubbles on the irradiated lesions.

Results

A total of 216 seborrheic keratoses were treated with a mean 1.1 ± 0.4 sessions of long‐pulsed 755‐nm alexandrite laser and achieved a mean objective improvement score of 3.4 ± 0.7. Morphologic factors significantly impacted the number of treatment sessions required; in particular, papular lesions seemed to require more repetitive long‐pulsed 755‐nm alexandrite laser treatments than macular lesions. However, objective improvement score was not affected by the type of the seborrheic keratoses. The colour of seborrheic keratoses did not significantly affect the objective improvement score or required treatment sessions. Most of the lesions became crusted within a few days after the laser treatment and spontaneously peeled off within 7 days.

Conclusions

The delivery of long‐pulsed, high fluence laser energy to seborrheic keratoses with protection of the epidermis by an integrated dynamic cooling device is an effective treatment with low risk of side‐effects, even in light‐coloured lesions with few target pigments.
Rosacea and cardiovascular risk factors: a case control study
Authors: Duman N. , Ersoy Evans S. , Atakan N.
Published: August 2013

Background and objective

Rosacea is an inflammatory skin disease with a chronic course. This study aimed to investigate the risk of cardiovascular disease (CVD) in rosacea patients.

Materials and methods

The study included 60 rosacea patients and 50 age‐ and gender‐matched controls. Demographic data, medical history, presence of cardiovascular risk factors were recorded. Waist circumference, height, and weight were measured, and the body mass index was calculated for each participant. Laboratory investigations, including fasting blood glucose, C‐reactive protein (CRP), very low‐density lipoprotein, low‐density lipoprotein (LDL), high‐density lipoprotein, total cholesterol, triglyceride, lipoprotein(a) were performed.

Results

In all, 66% of the rosacea patients were female (mean age: 44.65 ± 12.9 years) and 66% of the controls were female (mean age: 42.3 ± 12.3 years). Median disease duration in the rosacea group was 36 months. High total cholesterol (>200 mg/dL), LDL (>130 mg/dL) and CRP (>0.8 mg/L) levels, a family history of premature CVD, and a history of smoking and alcohol consumption were significantly more common in the rosacea patients compared to controls.

Conclusion

Rosacea patients may have a high risk of CVD. As such, we recommend close follow‐up of rosacea patients because of the increased risk of CVD. The mechanism underlying this increased risk is unknown, and additional randomized and controlled studies are required for clarification.
Temperature‐induced sex reversal is not responsible for sex‐ratio distortions in grayling Thymallus thymallus or brown trout Salmo trutta
Authors: Pompini M. , Buser A. M. , Thali M. R. , Von Siebenthal B. A. , Nusslé S. , Guduff S. , Wedekind C.
Published: August 2013

On the basis of the experiments carried out over various years, it was concluded that (1) grayling Thymallus thymallus and brown trout Salmo trutta are resistant to temperature‐induced sex reversal at ecologically relevant temperatures, (2) environmental sex reversal is unlikely to cause the persistent sex ratio distortion observed in at least one of the study populations and (3) sex‐specific tolerance of temperature‐related stress may be the cause of distorted sex ratios in populations of T. thymallus or S. trutta.
Psychiatric diagnostic screening of social maladaptive behaviour in children with mild intellectual disability: differentiating disordered attachment and pervasive developmental disorder behaviour
Authors: Giltaij H. P. , Sterkenburg P. S. , Schuengel C.
Published: August 2013

Background

Children with intellectual disability (ID) are at risk for maladaptive development of social relatedness. Controversy exists whether Pervasive Developmental Disorder (PDD) takes precedence over disordered attachment for describing maladaptive social behaviour. The aim of this study was to assess the prevalence of disordered attachment symptoms in children with ID referred for mental health diagnosis, and to study the potential diagnostic overlap between symptoms of disordered attachment and PDD symptoms.

Method

Children (n = 102) in the age of 5–11 with IDs (borderline or mild; IQ 50–85) referred for psychiatric consultation were recruited. Parents were administered a screening interview for disturbances of attachment and teachers were administered a screening questionnaire for PDD.

Results

Behavioural symptoms of disordered attachment were reported for 42%* of the children, with 16%* showing symptoms of inhibited and 37%* showing symptoms of disinhibited attachment disorder. In 11% both types of symptoms were noted. Attachment disorder symptoms were not significantly associated with gender, ethnic background or age. Positive screening for PDD occurred for 27%. Positive screening for PDD was not significantly associated with symptoms of attachment disorder.

Conclusions

Among children with ID referred for psychiatric consultation, Reactive Attachment Disorder (RAD) and PDD symptoms were both highly prevalent. RAD and PDD symptoms appear as distinct, but sometimes comorbid, forms of aberrant social relatedness.