bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of far-field acoustic emissions from cavitation clouds during shock wave lithotripsy for development of a clinical device
Authors: Leighton T. G. , Turangan C. K. , Jamaluddin A. R. , Ball G. J. , White P. R.
Published: December 2012

This study presents the key simulation and decision stage of a multi-disciplinary project to develop a hospital device for monitoring the effectiveness of kidney stone fragmentation by shock wave lithotripsy (SWL). The device analyses, in real time, the pressure fields detected by sensors placed on the patient's torso, fields generated by the interaction of the incident shock wave, cavitation, kidney stone and soft tissue. Earlier free-Lagrange simulations of those interactions were restricted (by limited computational resources) to computational domains within a few centimetres of the stone. Later studies estimated the far-field pressures generated when those interactions involved only single bubbles. This study extends the free-Lagrange method to quantify the bubble–bubble interaction as a function of their separation. This, in turn, allowed identification of the validity of using a model of non-interacting bubbles to obtain estimations of the far-field pressures from 1000 bubbles distributed within the focus of the SWL field. Up to this point in the multi-disciplinary project, the design of the clinical device had been led by the simulations. This study records the decision point when the project's direction had to be led by far more costly clinical trials instead of the relatively inexpensive simulations.
Thermal solitons: travelling waves in combustion
Authors: Forbes Lawrence K.
Published: December 2012

A competitive reaction system is considered, under which some chemical reagent decays by means of two simultaneous chemical reactions to form two separate inert products. One reaction is exothermic, and the other is endothermic. The governing equations for the model are presented, and a weakly nonlinear theory is then generated using the method of strained coordinates. Travelling-wave solutions are possible in the model, and the temperature is found to have a classical sech-squared profile. The stability of these moderate-amplitude temperature solitons is confirmed both analytically and numerically.
Sperm competition in tropical versus temperate zone birds
Authors: Albrecht Tomáš , Kleven Oddmund , Kreisinger Jakub , Laskemoen Terje , Omotoriogun Taiwo C. , Ottosson Ulf , Reif Jiří , Sedláček Ondřej , Hořák David , Robertson Raleigh J. , Lifjeld Jan T.
Published: December 2012

Sperm competition represents an important component of post-copulatory sexual selection. It has been argued that the level of sperm competition declines in birds towards the equator. However, to date, sperm competition estimates have been available mainly for avian species inhabiting the northern temperate zone. Here we apply a novel approach, using the coefficient of between-male variation (CVbm) in sperm size as an index for sperm competition risk, in a comparative analysis of 31 Afrotropical and 99 northern temperate zone passerine species. We found no difference in sperm competition risk between the two groups, nor any relationship with migration distance. However, a multivariate model indicated that sperm competition risk was highest in species with a combination of low body mass and few eggs per clutch. The effect of clutch size was most pronounced in tropical species, which indicates that sperm competition risk in tropical and temperate species is differently associated with particular life-history traits. Although tropical species had lower sperm competition risk than temperate zone species for overlapping clutch sizes, the idea of a generally reduced risk of sperm competition in tropical birds was not supported by our analysis.
Shared and unique morphological responses of stream fishes to anthropogenic habitat alteration
Authors: Franssen Nathan R. , Harris Jared , Clark Scott R. , Schaefer Jacob F. , Stewart Laura K.
Published: December 2012

Understanding population-level responses to novel selective pressures can elucidate evolutionary consequences of human-altered habitats. Stream impoundments (reservoirs) alter riverine ecosystems worldwide, exposing stream fishes to uncommon selective pressures. Assessing phenotypic trait divergence in reservoir habitats will be a first step in identifying the potential evolutionary and ecological consequences of stream impoundments. We tested for body shape divergence in four stream-adapted fishes found in both habitats within three separate basins. Shape variation among fishes was partitioned into shared (exhibited by all species) and unique (species-specific) responses to reservoir habitats. All fishes demonstrated consistent significant shared and unique morphological responses to reservoir habitats. Shared responses were linked to fin positioning, decreased body depths and larger caudal areas; traits likely related to locomotion. Unique responses were linked to head shape, suggesting species-specific responses to abiotic conditions or changes to their trophic ecology in reservoirs. Our results highlight how human-altered habitats can simultaneously drive similar and unique trait divergence in native populations.
A Cyclic Nucleotide-Gated Channel (CNGC16) in Pollen Is Critical for Stress Tolerance in Pollen Reproductive Development
Authors: Tunc-Ozdemir Meral , Tang Chong , Ishka Maryam Rahmati , Brown Elizabeth , Groves Norman R. , Myers Candace T. , Rato Claudia , Poulsen Lisbeth R. , McDowell Stephen , Miller Gad , Mittler Ron , Harper Jeffrey F.
Published: December 2012

Cyclic nucleotide-gated channels (CNGCs) have been implicated in diverse aspects of plant growth and development, including responses to biotic and abiotic stress, as well as pollen tube growth and fertility. Here, genetic evidence identifies CNGC16 in Arabidopsis (Arabidopsis thaliana) as critical for pollen fertility under conditions of heat stress and drought. Two independent transfer DNA disruptions of cngc16 resulted in a greater than 10-fold stress-dependent reduction in pollen fitness and seed set. This phenotype was fully rescued through pollen expression of a CNGC16 transgene, indicating that cngc16-1 and 16-2 were both loss-of-function null alleles. The most stress-sensitive period for cngc16 pollen was during germination and the initiation of pollen tube tip growth. Pollen viability assays indicate that mutant pollen are also hypersensitive to external calcium chloride, a phenomenon analogous to calcium chloride hypersensitivities observed in other cngc mutants. A heat stress was found to increase concentrations of 3′,5′-cyclic guanyl monophosphate in both pollen and leaves, as detected using an antibody-binding assay. A quantitative PCR analysis indicates that cngc16 mutant pollen have attenuated expression of several heat-stress response genes, including two heat shock transcription factor genes, HsfA2 and HsfB1. Together, these results provide evidence for a heat stress response pathway in pollen that connects a cyclic nucleotide signal, a Ca2+-permeable ion channel, and a signaling network that activates a downstream transcriptional heat shock response.
UBIQUITIN-SPECIFIC PROTEASE16 Modulates Salt Tolerance in Arabidopsis by Regulating Na+/H+ Antiport Activity and Serine Hydroxymethyltransferase Stability
Authors: Zhou Huapeng , Zhao Jinfeng , Yang Yongqing , Chen Changxi , Liu Yanfen , Jin Xuehua , Chen Limei , Li Xueyong , Deng Xing Wang , Schumaker Karen S. , Guo Yan
Published: December 2012

Protein ubiquitination is a reversible process catalyzed by ubiquitin ligases and ubiquitin-specific proteases (UBPs). We report the identification and characterization of UBP16 in Arabidopsis thaliana. UBP16 is a functional ubiquitin-specific protease and its enzyme activity is required for salt tolerance. Plants lacking UBP16 were hypersensitive to salt stress and accumulated more sodium and less potassium. UBP16 positively regulated plasma membrane Na+/H+ antiport activity. Through yeast two-hybrid screening, we identified a putative target of UBP16, SERINE HYDROXYMETHYLTRANSFERASE1 (SHM1), which has previously been reported to be involved in photorespiration and salt tolerance in Arabidopsis. We found that SHM1 is degraded in a 26S proteasome–dependent process, and UBP16 stabilizes SHM1 by removing the conjugated ubiquitin. Ser hydroxymethyltransferase activity is lower in the ubp16 mutant than in the wild type but higher than in the shm1 mutant. During salt stress, UBP16 and SHM1 function in preventing cell death and reducing reactive oxygen species accumulation, activities that are correlated with increasing Na+/H+ antiport activity. Overexpression of SHM1 in the ubp16 mutant partially rescues its salt-sensitive phenotype. Taken together, our results suggest that UBP16 is involved in salt tolerance in Arabidopsis by modulating sodium transport activity and repressing cell death at least partially through modulating SMH1stability and activity.
Diaquaiodidotetrasarcosinepotassium: an overview of sarcosine metal halogenide structures
Authors: Fleck Michel , Ghazaryan Vahram V. , Petrosyan Aram M.
Published: December 2012

The monoclinic crystal structure of tetrasarcosine potassium iodide dihydrate {orcatena-poly[[potassium-tetra-μ-sarcosine-κ4O:O′;κ4O:O] iodide dihydrate]}, {[K(C3H7NO2)4]I·2H2O}nor Sar4·KI·2H2O (space groupC2/c), comprises two crystallographically different sarcosine molecules and one water molecule on general positions, and one K+cation and one I−anion located on twofold axes. The irregular eight-coordinated K+polyhedra are connected into infinite chains along [001]viasarcosine molecules. This compound is the first sarcosine metal halogenide salt with a 4:1 ratio. A short overview of other sarcosine metal halogenide salts is presented and relationships to similar glycine salts are discussed.
Erythrocyte membrane transporters during human ageing: Modulatory role of tea catechins
Authors: Pandey Kanti Bhooshan , Jha Rashmi , Rizvi Syed Ibrahim
Published: December 2012

Ageing is associated with many physiological and cellular changes, many of which are due to alterations in the plasma membrane. The functions of membrane transporter proteins are crucial for the maintenance of ionic homeostasis between the extra‐ and intracellular environments.

The aim of the present study was to determine the status of erythrocyte membrane transporters, specifically Ca2+‐ATPases, Na+/K+‐ATPases and the Na+/H+ exchanger (NHE), during ageing in humans. Furthermore, because tea catechins have been reported to possess strong anti‐oxidant potential, the study was extended to evaluate the effect of (–)‐epicatechin (EC), (–)‐epicatechin‐3‐gallate (ECG), (–)‐epigallocatechin (EGC) and (–)‐epigallocatechin‐3‐gallate (EGCG) on these transporters as a function of human age.

The study was performed on 97 normal healthy subjects (62 men, 35 women; 16–80 years old). To investigate the effects of tea catechins, subjects were divided into three groups: young (<40 years old; n = 34); middle‐aged (40–60 years old; n = 32); and old (>60 years old; n = 31). Erythrocyte ghosts/cell suspension from each group were incubated with ECG, EGCG, EGC and EC (10 μmol/L) for 30 min at 37°C prior to assay.

Ageing significantly increased NHE activity and decreased Ca2+‐ATPase activity. There were no significant changes in Na+/K+‐ATPase activity during the ageing process.

(–)‐Epigallocatechin‐3‐gallate, EGC, ECG and EC effectively mitigated the changes in membrane transporter activity in erythrocytes from all age groups; however, the effect was more pronounced in the old age group.

We hypothesize that impairment in ‐bound transporters may be one of the possible mechanisms underlying the pathological events during ageing. A higher intake of catechin‐rich food may provide some protection against age‐dependent diseases.
High‐throughput isolation of giant viruses of the Mimiviridae and Marseilleviridae families in the Tunisian environment
Authors: Boughalmi Mondher , Saadi Hanene , Pagnier Isabelle , Colson Philippe , Fournous Ghislain , Raoult Didier , La Scola Bernard
Published: December 2012

Giant viruses of the Megavirales order have been recently isolated from aquatic environments and have long been neglected because they are removed from samples during viral purification for viral metagenomic studies. Due to bacterial overgrowth and susceptibility to high concentrations of antibiotics, isolation by amoeba co‐culture has a low efficiency and is highly time‐consuming. Thus, few environments have been exhaustively investigated to date, although the ubiquitous distribution of the Acanthamoeba sp. suggests that these viruses could also be ubiquitous. In this work, we have implemented a high‐throughput method to detect amoebae lysis on agar plates that allows the testing of hundreds of samples in a few days. Using this procedure, a total of 11 new Marseilleviridae strains and four new Mimiviridae strains, including a virus infected with a virophage, were isolated from 1000 environmental samples from Tunisia. Of these, four corresponded to new genotypic variants. These isolates are the first African environmental isolates identified from these two families, and several samples were obtained from a hypersaline aquatic environment. These results demonstrate that this technique can be used for the evaluation and characterization of large collections of giant viruses to provide insight into understanding their ecology.
The Entner–Doudoroff pathway empowers Pseudomonas putida KT2440 with a high tolerance to oxidative stress
Authors: Chavarría Max , Nikel Pablo I. , Pérez‐Pantoja Danilo , de Lorenzo Víctor
Published: December 2012

Glucose catabolism of Pseudomonas putida is carried out exclusively through the Entner–Doudoroff (ED) pathway due to the absence of 6‐phosphofructokinase. In order to activate the Embden–Meyerhof–Parnas (EMP) route we transferred the pfkA gene from Escherichia coli to a P. putida wild‐type strain as well as to an eda mutant, i.e. lacking 2‐keto‐3‐deoxy‐6‐phosphogluconate aldolase. PfkAE. coli failed to redirect the carbon flow from the ED route towards the EMP pathway, suggesting that ED was essential for sugar catabolism. The presence of PfkAE. coli was detrimental for growth, which could be traced to the reduction of ATP and NAD(P)H pools along with alteration of the NAD(P)H/NADP+ ratio. Pseudomonas putida cells carrying PfkAE. coli became highly sensitive to diamide and hydrogen peroxide, the response to which is very demanding of NADPH. The inhibitory effect of PfkAE. coli could in part be relieved by methionine, the synthesis of which relies much on NADPH. These results expose the role of the ED pathway for generating the redox currency (NADPH) that is required for counteracting oxidative stress. It is thus likely that environmental bacteria that favour the ED pathway over the EMP pathway do so in order to gear their aerobic metabolism to endure oxidative‐related insults.
Global Functional Connectivity Abnormalities in Children with Fetal Alcohol Spectrum Disorders
Authors: Wozniak Jeffrey R. , Mueller Bryon A. , Bell Christopher J. , Muetzel Ryan L. , Hoecker Heather L. , Boys Christopher J. , Lim Kelvin O.
Published: December 2012

Background

Previous studies, including those employing diffusion tensor imaging (DTI), have revealed significant disturbances in the white matter of individuals with fetal alcohol spectrum disorders (FASD). Both macrostructural and microstructural abnormalities have been observed across levels of FASD severity. Emerging evidence suggests that these white matter abnormalities are associated with functional deficits. This study used resting‐state functional MRI (fMRI) to evaluate the status of network functional connectivity in children with FASD compared with control subjects.

Methods

Participants included 24 children with FASD, ages 10 to 17, and 31 matched controls. Neurocognitive tests were administered including Wechsler Intelligence Scales, California Verbal Learning Test (CVLT), and Behavior Rating Inventory of Executive Functioning. High‐resolution anatomical MRI data and 6‐minute resting‐state fMRI data were collected. The resting‐state fMRI data were subjected to a graph theory analysis, and 4 global measures of cortical network connectivity were computed: characteristic path length, mean clustering coefficient, local efficiency, and global efficiency.

Results

Results revealed significantly altered network connectivity in those with FASD. The characteristic path length was 3.1% higher (p = 0.04, Cohen's d = 0.47), and global efficiency was 1.9% lower (p = 0.04, d = 0.63) in children with FASD compared with controls, suggesting decreased network capacity that may have implications for integrative cognitive functioning. Global efficiency was significantly positively correlated with cortical thickness in frontal (r = 0.38, p = 0.005), temporal (r = 0.28, p = 0.043), and parietal (r = 0.36, p = 0.008) regions. No relationship between facial dysmorphology and functional connectivity was observed. Exploratory correlations suggested that global efficiency and characteristic path length are associated with capacity for immediate verbal memory on the CVLT (r = 0.41, p = 0.05 and r = 0.41, p = 0.01, respectively) among those with FASD.

Conclusions

Resting‐state functional connectivity measures provide new insight into the integrity of brain networks in clinical populations such as FASD. Results demonstrate that children with FASD have alterations in core components of network function and that these aspects of brain integrity are related to measures of structure and cognitive functioning.
Neural network activation during a stop‐signal task discriminates cocaine‐dependent from non‐drug‐abusing men
Authors: Elton Amanda , Young Jonathan , Smitherman Sonet , Gross Robin E. , Mletzko Tanja , Kilts Clinton D.
Published: December 2012

Cocaine dependence is defined by a loss of inhibitory control over drug‐use behaviors, mirrored by measurable impairments in laboratory tasks of inhibitory control. The current study tested the hypothesis that deficits in multiple subprocesses of behavioral control are associated with reliable neural‐processing alterations that define cocaine addiction. While undergoing functional magnetic resonance imaging (fMRI), 38 cocaine‐dependent men and 27 healthy control men performed a stop‐signal task of motor inhibition. An independent component analysis on fMRI time courses identified task‐related neural networks attributed to motor, visual, cognitive and affective processes. The statistical associations of these components with five different stop‐signal task conditions were selected for use in a linear discriminant analysis to define a classifier for cocaine addiction from a subsample of 26 cocaine‐dependent men and 18 controls. Leave‐one‐out cross‐validation accurately classified 89.5% (39/44; chance accuracy = 26/44 = 59.1%) of subjects with 84.6% (22/26) sensitivity and 94.4% (17/18) specificity. The remaining 12 cocaine‐dependent and 9 control men formed an independent test sample, for which accuracy of the classifier was 81.9% (17/21; chance accuracy = 12/21 = 57.1%) with 75% (9/12) sensitivity and 88.9% (8/9) specificity. The cocaine addiction classification score was significantly correlated with a measure of impulsiveness as well as the duration of cocaine use for cocaine‐dependent men. The results of this study support the ability of a pattern of multiple neural network alterations associated with inhibitory motor control to define a binary classifier for cocaine addiction.
Alcohol drinking and deprivation alter basal extracellular glutamate concentrations and clearance in the mesolimbic system of alcohol‐preferring (P) rats
Authors: Ding Zheng‐Ming , Rodd Zachary A. , Engleman Eric A. , Bailey Jason A. , Lahiri Debomoy K. , McBride William J.
Published: December 2012

The present study determined the effects of voluntary ethanol drinking and deprivation on basal extracellular glutamate concentrations and clearance in the mesolimbic system and tested the hypothesis that chronic ethanol drinking would persistently increase basal glutamate neurotransmission. Three groups of alcohol‐preferring (P) rats were used: ‘water group (WG),’ ‘ethanol maintenance group (MG; 24‐hour free choice water versus 15% ethanol)’ and ‘ethanol deprivation group (DG; 2 weeks of deprivation).’ Quantitative microdialysis and Western blots were conducted to measure basal extracellular glutamate concentrations, clearance and proteins associated with glutamate clearance. Chronic alcohol drinking produced a 70–100% increase of basal extracellular glutamate concentrations in the posterior ventral tegmental area (4.0 versus 7.0 μM) and nucleus accumbens shell (3.0 versus 6.0 μM). Glutamate clearances were reduced by 30–40% in both regions of MG rats compared with WG rats. In addition, Western blots revealed a 40–45% decrease of excitatory amino transporter 1 (EAAT1) protein, but no significant changes in the levels of EAAT2 or cystine‐glutamate antiporter in these regions of MG versus WG rats. The enhanced glutamate concentrations returned to control levels, accompanied by a recovery of glutamate clearance following deprivation. These results indicated that chronic alcohol drinking enhanced extracellular glutamate concentrations in the mesolimbic system, as a result, in part, of reduced clearance, suggesting that enhanced glutamate neurotransmission may contribute to the maintenance of alcohol drinking. However, because the increased glutamate levels returned to normal after deprivation, elevated glutamate neurotransmission may not contribute to the initiation of relapse drinking.
Accuracy of the Dentaport ZX apex locator for working length determination when retreating molar root canals
Authors: Cimilli Hale , Aydemir Seda , Arıcan Burcin , Mumcu Gonca , Chandler Nicholas , Kartal Nevin
Published: December 2012

The aim of this study was to evaluate the accuracy of the Dentaport ZX apex locator for working length determination during root canal retreatment of mandibular molars. Fifteen extracted mandibular first molars with separate mesial canals and apical foraminae and one distal canal were selected. The mesiobuccal and distal canals were investigated; the length with the file tip at the major diameter was defined as the tooth length (TL). The canals were prepared with ProTaper files to 1 mm short of this and filled with gutta‐percha and AH Plus sealer. One week later, the root fillings were removed using ProTaper retreatment files. Tooth length was remeasured and recorded as the retreatment tooth length (RTL). Then electronic measurements were taken at the major (electronic apex locator (EAL) major) and minor (EAL minor) foraminae as suggested by the instrument display. These lengths were compared with RTL and measurements 0.5 and 1 mm short of this distance. For both canals, no significant difference was found between RTL and EAL major, and 0.5 mm short of RTL and EAL minor (P > 0.05). There were significant differences found between all other readings. The Dentaport ZX could not detect the minor foramen accurately but was able to indicate the major foramen in molars undergoing a root canal retreatment procedure.
Compositional Analysis of 14th–15th Century Enamels from the Altar of San Giovanni in Florence: an Integrated Study by Portable X‐Ray Fluorescence and Electron Probe Microanalysis
Authors: Verità M. , Cagnini A. , Galeotti M. , Cavalca N. , Porcinai S.
Published: December 2012

The enamels of the Altar of San Giovanni, from the Baptistery of Florence, were investigated using both non‐invasive and micro‐invasive analysis in order to elucidate the glass melting and colouring techniques. A few fragments detached from the altar and recovered by the restorers were analysed in cross‐section by electron probe microanalysis. Moreover, non‐invasive investigations by portable XRF allowed a large number of enamelled plaques to be investigated. The results showed a good agreement between the two techniques and made it possible to identify similarities or differences in the enamels of the three manufacturing periods of the altar.
The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144)
Authors: Nolen Willem A , Weisler Richard H
Published: December 2012

Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144).  Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd.

Objectives:  There is no robust proof that the efficacy of lithium in the prevention of manic and depressive episodes in bipolar disorder depends on its plasma level. This analysis aimed to compare the effect of lithium within the presumed therapeutic range of 0.6–1.2 mEq/L and below 0.6 mEq/L with that of placebo.

Methods:  We carried out a post hoc analysis of a double‐blind trial in which patients aged ≥18 years with bipolar I disorder (DSM‐IV) who had achieved stabilization from a manic, depressive, or mixed episode during open‐label treatment with quetiapine were randomized to continue quetiapine or to switch to lithium or placebo for up to 104 weeks. Of patients randomized to lithium, 201 obtained median lithium levels between 0.6 and 1.2 mEq/L, and 137 obtained median lithium levels <0.6 mEq/L. Their outcomes were compared with those of patients receiving placebo (n = 404). The primary outcome was time to recurrence of any mood event; additional outcomes included time to recurrence of a manic or depressive event.

Results:  Times to recurrence of any mood event as well as a manic or depressive event were significantly longer for the lithium 0.6–1.2 mEq/L group versus placebo and versus lithium <0.6 mEq/L, with no differences between lithium <0.6 mEq/L and placebo.

Conclusions:  The results support and expand previous findings that lithium should be dosed high enough to achieve plasma levels ≥0.6 mEq/L in order to achieve an effect in the prevention of both manic and depressive recurrences of bipolar I disorder. A major limitation is that the composition of the two lithium groups was not based on randomization.
Students' engagement in technology rich classrooms and its relationship to professors' conceptions of effective teaching
Authors: Gebre Engida , Saroyan Alenoush , Bracewell Robert
Published: December 2012

This study examined dimensions of student engagement in technology rich classrooms and the relationship of this engagement to professors' conceptions of effective teaching. We collected questionnaire data from 332 students and analysed the data in relation to the finding of another study (Authors, forthcoming) involving 13 professors' course‐specific conceptions of effective teaching. Principal component analysis with varimax rotation revealed four dimensions of student engagement: cognitive and applied engagement, social engagement, reflective engagement and goal clarity. Subsequent multivariate and univariate analyses of variance showed that the extent of students' cognitive and applied engagement and social engagement is related significantly to professors' conceptions of effective teaching. The study has implication on design and assessment of technology‐rich learning environments and on faculty development programs involving technology use in their teaching.
Arterial and venous thrombosis in patients with monoclonal gammopathy of undetermined significance: incidence and risk factors in a cohort of 1491 patients
Authors: Za Tommaso , De Stefano Valerio , Rossi Elena , Petrucci Maria Teresa , Andriani Alessandro , Annino Luciana , Cimino Giuseppe , Caravita Tommaso , Pisani Francesco , Ciminello Angela , Torelli Fabio , Villivà Nicoletta , Bongarzoni Velia , Rago Angela , Betti Silvia , Levi Anna , Felici Stefano , Gentilini Fabiana , Calabrese Elisabetta , Leone Giuseppe ,   the Multiple Myeloma GIMEMA‐Latium Region Working Group
Published: December 2012

Monoclonal gammopathy of undetermined significance (MGUS) has been associated with an increased risk of thrombosis. We carried out a retrospective multicentre cohort study on 1491 patients with MGUS. In 49 patients (3·3%) MGUS was diagnosed after a thrombotic event. Follow‐up details for a period of at least 12 months after diagnosis of MGUS were obtained in 1238 patients who had no recent history of thrombosis (<2 years) prior to diagnosis, for a total of 7334 years. During the follow‐up, 33 of 1238 patients (2·7%) experienced thrombosis, with an incidence of 2·5 arterial events and 1·9 venous events per 1000 patient‐years. Multivariate analysis showed increased risks of arterial thrombosis in patients with cardiovascular risk factors [hazard ratio (HR) 4·92, 95%confidence interval (CI) 1·42–17·04], and of venous thrombosis in patients with a serum monoclonal (M)‐protein level >16 g/l at diagnosis (HR 3·08, 95%CI 1·01–9·36). No thrombosis was recorded in patients who developed multiple myeloma (n = 50) or other neoplastic diseases (n = 21). The incidence of arterial or venous thrombosis in patients with MGUS did not increase relative to that reported in the general population for similarly aged members. Finally, the risk of venous thrombosis did increase when the M‐protein concentration exceeded >16 g/l.
Incidence and Predictors of Atrial Septal Defect after Percutaneous Transvenous Mitral Commissurotomy – A Transesophageal Echocardiographic Study of 209 Cases
Authors: Manjunath Chollenahally Nanjappa , Panneerselvam Arunkumar , Srinivasa Kikkeri Hemanna Setty , Prabhavathi Bhat , Rangan Kapil , Dhanalakshmi Chandrasekaran , Ravindranath Khandenahally Shankarappa
Published: December 2012

Background: The incidence of atrial septal defect (ASD) after percutaneous transvenous mitral commissurotomy (PTMC) ranges from 15.2% to 92% in small studies. Aim: To estimate the incidence of atrial septal defect (ASD) following PTMC and to determine the factors contributing to its development. Methods: We studied 209 patients with mitral stenosis (MS) undergoing PTMC. Transesophageal echocardiography (TEE) with color Doppler examination was performed to detect ASD. Results: TEE demonstrated ASD in 139 (66.5%) of 209 patients. The mean diameter of the interatrial septal defect detected by TEE was 4.47 ± 1.7 mm. The most common site of septal puncture was the inferior vena caval side of the interatrial septum followed by fossa ovalis. Color flow imaging across the defect showed left to right shunting in all the patients (100%). We examined the relationship of age, Wilkins score, left atrial volumes, the mitral valve orifice area, mitral valve gradient, and the degree of mitral and tricuspid regurgitation between the group that developed ASD and the group without ASD and found that none of these factors predicted the development of ASD. A residual ASD was seen in 11 patients (8.7%) at 6‐month follow‐up. Conclusion: Incidence of residual atrial septal defect immediately following PTMC by TEE color flow Doppler imaging is 66.5%. Surrogate markers of elevated left atrial pressures do not determine the development of atrial septal defect after PTMC. The majority of the defects close spontaneously and a residual defect is observed in 8.7% patients at 6 months.
High Incidence of Echocardiographic Abnormalities of the Interatrial Septum in Patients Undergoing Ablation for Atrial Fibrillation
Authors: Schernthaner Christiana , Danmayr Franz , Daburger Apollonia , Eichinger Jörg , Hammerer Matthias , Strohmer Bernhard
Published: December 2012

Background: Atrial fibrosis or fatty deposition is known to increase the propensity for the development of atrial fibrillation (AF). Apart from the pulmonic veins, the interatrial septum (IAS) might play a role in the maintenance of AF. In contrast to left atrial anatomy and adjacent veins, the IAS cannot be visualized in detail with computed tomography. Thus, preprocedural transesophageal echocardiography (TEE) may provide important morphologic information beyond exclusion from atrial thrombi. Methods: The study comprised 108 consecutive patients (mean age 60 ± 11 years; 98 men). AF was paroxysmal in 91 (84%) and persistent in 17 (16%) patients. We investigated the morphological characteristics of the IAS by TEE in patients who underwent radiofrequency ablation of AF. Results: The IAS was structurally abnormal in 46 (43%) patients, showing the following echocardiograhic findings: atrial septal hypermobility or aneurysm (n = 27) associated with a patent foramen ovale (PFO) (n = 11) or with a small atrial septal defect (ASD) (n = 2), a septal flap associated with a PFO or an ASD (n = 8), and an abnormally thickened IAS (n = 12). A thrombus in the left atrial appendage was discovered in only 2 (2%) patients. Conclusions: A structurally abnormal IAS was diagnosed in nearly half of the patients undergoing ablation therapy for AF. The information obtained by TEE is mandatory to exclude left atrial thrombi prior the ablation procedure. Moreover, detailed knowledge of morphologic characteristics of the IAS facilitates an optimized and safe performance of the transseptal puncture using long sheaths with large diameters.
A Voluminous Right Atrial Myxoma Revealed by Right Side Heart Failure
Authors: Nazzi Mbarek , Belhachmi Hassan , Badidi Mehdi , Zbir Elmehdi , Mohty Dania
Published: December 2012

Mini‐Abstract

Right atrial myxoma is rare. Its clinical presentation is polymorphic. The most common presentation is heart failure, but could be pulmonary embolism or tricuspid valve obstruction. We report here, the case of a 60‐year‐old man admitted for severe heart failure. The echocardiogram showed a voluminous and floating right atrial mass, appending to the interatrial septum and protruding into the right ventricle causing severe tricuspid regurgitation. Chest computed tomography scan demonstrated multiple distal pulmonary emboli. Surgical excision and tricuspid annuloplasty were successfully performed. Histological findings were typical of a benign myxoma. At follow‐up, there was a complete regression of heart failure signs.
Species interactions constrain geographic range expansion over evolutionary time
Authors: Pigot Alex L. , Tobias Joseph A.
Published: December 2012

Whether biotic interactions limit geographic ranges has long been controversial, and traditional analyses of static distribution patterns have made little progress towards resolving this debate. Here, we use a novel phylogenetic approach to test whether biotic interactions constrain the transition to secondary sympatry following speciation. Applying this temporal framework to a diverse clade of passerine birds (Furnariidae), we reject models of geographic range overlap limited purely by dispersal or environmental constraints, and instead show that rates of secondary sympatry are positively associated with both the phylogenetic and morphological distance between species. Thus, transition rates to sympatry increase with time since divergence and accelerate as the ecological differences between species accumulate. Taken together, these results provide strong empirical evidence that biotic interactions – and primarily ecological competition – limit species distributions across large spatial and temporal scales. They also offer phylogenetic and trait‐based metrics by which these interactions can be incorporated into ecological forecasting models.
Understanding pathogenic single‐nucleotide polymorphisms in multidomain proteins – studies of isolated domains are not enough
Authors: Randles Lucy G. , Dawes Gwen J. S. , Wensley Beth G. , Steward Annette , Nickson Adrian A. , Clarke Jane
Published: December 2012

Studying the effects of pathogenic mutations is more complex in multidomain proteins when compared with single domains: mutations occurring at domain boundaries may have a large effect on a neighbouring domain that will not be detected in a single‐domain system. To demonstrate this, we present a study that utilizes well‐characterized model protein domains from human spectrin to investigate the effect of disease‐ and non‐disease‐causing single point mutations occurring at the boundaries of human spectrin repeats. Our results show that mutations in the single domains have no clear correlation with stability and disease; however, when studied in a tandem model system, the disease‐causing mutations are shown to disrupt stabilizing interactions that exist between domains. This results in a much larger decrease in stability than would otherwise have been predicted, and demonstrates the importance of studying such mutations in the correct protein context.
X‐ray crystallography and NMR studies of domain‐swapped canecystatin‐1
Authors: Valadares Napoleão F. , de Oliveira‐Silva Rodrigo , Cavini Italo A. , de Almeida Marques Ivo , D'Muniz Pereira Humberto , Soares‐Costa Andrea , Henrique‐Silva Flavio , Kalbitzer Hans R. , Munte Claudia E. , Garratt Richard C.
Published: December 2012

The three‐dimensional structure of canecystatin‐1, a potent inhibitor of cysteine proteases from sugarcane (Saccharum officinarum), has been solved in two different crystal forms. In both cases, it is seen to exist as a domain‐swapped dimer, the first such observation for a cystatin of plant origin. Size exclusion chromatography and multidimensional NMR spectroscopy show the dimer to be the dominant species in solution, despite the presence of a measurable quantity of monomer undergoing slow exchange. The latter is believed to be the active species, whereas the domain‐swapped dimer is presumably inactive, as its first inhibitory loop has been extended to form part of a long β‐strand that forms a double‐helical coiled coil with its partner from the other monomer. A similar structure is observed in human cystatin C, but the spatial disposition of the two lobes of the dimer is rather different. Dimerization is presumably a mechanism by which canecystatin‐1 can be kept inactive within the plant, avoiding the inhibition of endogenous proteases. The structure described here provides a platform for the rational design of specific cysteine protease inhibitors for biotechnological applications.

Database

The coordinates and structure factors have been deposited in the Protein Data Bank under the accession codes 3UL5 and 3UL6.

Structured digital abstract

Canecystatin-1 and Canecystatin-1 bind by molecular sieving (View Interaction: 1, 2)

Canecystatin-1 and Canecystatin-1 bind by nuclear magnetic resonance (View interaction)

Canecystatin-1 and Canecystatin-1 bind by dynamic light scattering (View interaction)

Canecystatin-1 and Canecystatin-1 bind by x-ray crystallography (View interaction)
Association study of 37 genes related to serotonin and dopamine neurotransmission and neurotrophic factors in cocaine dependence
Authors: Fernàndez‐Castillo N. , Roncero C. , Grau‐Lopez L. , Barral C. , Prat G. , Rodriguez‐Cintas L. , Sánchez‐Mora C. , Gratacòs M. , Ramos‐Quiroga J.A. , Casas M. , Ribasés M. , Cormand B.
Published: December 2012

Cocaine dependence is a neuropsychiatric disorder in which both environmental and genetic factors are involved. Several processes, that include reward and neuroadaptations, mediate the transition from use to dependence. In this regard, dopamine and serotonin neurotransmission systems are clearly involved in reward and other cocaine‐related effects, whereas neurotrophic factors may be responsible for neuroadaptations associated with cocaine dependence. We examined the contribution to cocaine dependence of 37 genes related to the dopaminergic and serotoninergic systems, neurotrophic factors and their receptors through a case–control association study with 319 single nucleotide polymorphisms selected according to genetic coverage criteria in 432 cocaine‐dependent patients and 482 sex‐matched unrelated controls. Single marker analyses provided evidence for association of the serotonin receptor HTR2A with cocaine dependence [rs6561333; nominal P‐value adjusted for age = 1.9e−04, odds ratio = 1.72 (1.29–2.30)]. When patients were subdivided according to the presence or absence of psychotic symptoms, we confirmed the association between cocaine dependence and HTR2A in both subgroups of patients. Our data show additional evidence for the involvement of the serotoninergic system in the genetic susceptibility to cocaine dependence.
CpG ODN‐induced matrix metalloproteinase‐13 expression is mediated via activation of the ERK and NF‐κB signalling pathways in odontoblast cells
Authors: Zhang J. , Zhu Q. L. , Huang P. , Yu Q. , Wang Z. H. , Cooper P. R. , Smith A. J. , He W.
Published: December 2012

Aim

To investigate the effects of CpG ODN (CpG oligodeoxynucleotides) to model the action of bacterial challenge on pulpal matrix metalloproteinase‐13 (MMP‐13) expression and elucidate the associated intracellular signalling pathways.

Methodology

Real‐time PCR was used to detect the effects of CpG ODN on MMP‐13 mRNA expression levels in a murine odontoblast‐lineage cell line (OLCs). The possible involvement of TLR9/MyD88, NF‐κB or MAPK pathways involved in the CpG ODN‐induced MMP‐13 expression was examined by real‐time PCR, transient transfection, luciferase activity assay and ELISA. Western blotting was performed to assay the phosphorylation of ERK at a range of time points.

Results

MMP‐13 was constitutively expressed in OLCs, and their exposure to CpG ODN significantly increased MMP‐13 expression. Pre‐treatment of OLCs with the inhibitory peptide MyD88, or chloroquine, attenuated the CpG ODN‐induced expression of MMP‐13. Treatment of the OLCs with CpG ODN increased NF‐κB‐luciferase activity. This activity was decreased by the over‐expression of a nondegrading mutant of IκBα (IκBαSR), although enhanced by the over‐expression of NF‐κB p65. MMP‐13 expression induced by CpG ODN was markedly suppressed by NF‐κB inhibitors (pyrrolidine dithiocarbamate, PDTC), IκBα phosphorylation inhibitors (Bay 117082) or IκB protease inhibitor (L‐1‐tosylamido‐2‐phenylethyl chloromethyl ketone, TPCK). The inhibitor of ERK1/2, U0126, but not inhibitors of p38 MAPK and JNK, SB203580 and SP600125, decreased CpG ODN‐mediated MMP‐13 expression.

Conclusion

The CpG ODN‐induced MMP‐13 expression in OLCs is mediated through TLR9, NF‐κB and the ERK pathway indicating that potentially the recognition of CpG ODN by TLR9 on odontoblasts may regulate the remodelling of injured dental pulp and hard tissues by inducing MMP‐13 expression.
Effect of the stable prostacyclin analogue iloprost on water and electrolyte transfer of the rat ileum and colon in vivo
Authors: GOERG K. J. , WANITSCHKE R. , BECKER U. , BÜSCHENFELDE K.‐H. MEYER ZUM
Published: December 2012

Abstract. The effect of iloprost on water and ion transfer was measured simultaneously in tied‐off loops of the rat ileum and colon in vivo. (1) In the ileal loops iloprost had no effect on water and ion transfer neither by intraluminal, nor intraaortal or intravenous application. (2) In the colonic loops only intraaortal bolus application of the high dose of 500 μg iloprost significantly decreased net water, sodium and chloride absorption, but did not induce net secretion. (3) Inhibition of endogenous prostaglandin synthesis by indomethacin did not change net water and electrolyte transfer in the ileum and colon. (4) Under this pretreatment i.v.‐application of 100 μg iloprost, ineffective without indomethacin, induced a net secretion of water and sodium and inhibited absorption of chloride in the colon. (5) At the same time iloprost had no effect in the ileal loops of the same animals. (6) Potassium secretion was activated already by 100 μg iloprost administered intraluminally. We conclude from this study, that prostacyclin and iloprost have a specific secretory action in the colon. However this effect is masked under in‐vivo conditions, either by interactions of ineffective prostaglandin metabolites with the concerned receptors or by counteracting prostaglandins, and becomes evident only after inhibition of the prostaglandin biosynthesis.
The effect of long‐term fibre and starch intake by man on faecal bile acid excretion
Authors: GHOOS Y. , RUTGEERTS P. , VANTRAPPEN G. , HIELE M. , SCHURMANS P.
Published: December 2012

Abstract. Parameters of bile acid metabolism were studied in two populations with different dietary fibre and starch intake over a period of at least 5 years. Subjects with a high fibre and starch intake have significant increases in faecal wet weight (288·5 g day−1 vs. 136·1), faecal dry weight (39·3 g day−1 vs. 20·2), faecal bile acid excretion (3930 mg day−1 vs. 115·4) and faecal bile acid:faecal dry weight ratio (13·6 vs. 5·8). There was no difference in bowel transit time measured with 3H‐PEG 4000 as marker of the liquid phase. The cumulative 14CO2 excretion during the bile acid breath test was higher in the high‐fibre group, compared with the low‐fibre group (4·6% dose cumulative at 8 h vs. 2·5%). Serum triglyceride and cholesterol levels were comparable in both groups. It is suggested that increased faecal weight and bile acid secretion is due to the synergic effect of high fibre and starch intake upon colonic bacterial proliferation.
Peptide hormones in patients with acute leukaemia
Authors: PFLÜGER K.‐H. , KÖPPLER H. , JAQUES G. , HAVEMANN K.
Published: December 2012

Abstract. Paraneoplastic production and secretion of peptide hormones by numerous malignant tumours is a well‐known phenomenon. The incidence of the production of six peptide hormones was evaluated in patients with acute leukaemia. Most often the calcitonin gene‐related peptides were found to be elevated in sera at the time of diagnosis. The values evaluated for the hormones were: h‐CT 46·7%, CGRP 51%, s‐CT 20·7%, PTH 15·7%, β‐HCG 15%, and ACTH 11·6%. A significant coincidence of two or more hormones was not observed. In 83·4% of the patients increased concentrations of at least one of the six hormones were found. Clinical and biochemical parameters showed no influence on the serum levels of these peptides. Analysis of elevated hormone serum levels in subtypes of leukaemia revealed that the calcitonin‐related hormones were significantly correlated to more immature forms of leukaemia such as AUL and M1. Synthesis of calcitonin gene‐related peptides was also seen in established leukaemic cell lines and in buffy coat cells of untreated patients with acute leukaemia. This investigation provides further evidence that peptide hormone production in leukaemic blasts is a common finding. These results further suggest hormone production to be a universal concommitant of neoplasia. A possible influence of these peptide hormones on the biological behaviour of the malignant cells is discussed.