bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of ultra low-k nanoporous and fluorinated silica based films prepared by plasma enhanced chemical vapor deposition
Authors: Abbasi-Firouzjah M. , Shokri B.
Published: December 2013

Low dielectric constant (low-k) silica based films were deposited on p-type silicon and polycarbonate substrates by radio frequency (RF) plasma enhanced chemical vapor deposition method at low temperature. A mixture of tetraethoxysilane vapor, oxygen, and tetrafluoromethane (CF4) was used for the deposition of the films in forms of two structures called as SiOxCy and SiOxCyFz. Properties of the films were controlled by amount of porosity and fluorine content in the film matrix. The influence of RF power and CF4 flow on the elemental composition, deposition rate, surface roughness, leakage current, refractive index, and dielectric constant of the films were characterized. Moreover, optical emission spectroscopy was applied to monitor the plasma process at the different parameters. Electrical characteristics of SiOxCy and SiOxCyFz films with metal-oxide-semiconductor structure were investigated using current-voltage analysis to measure the leakage current and breakdown field, as well as capacitance-voltage analysis to obtain the film's dielectric constant. The results revealed that SiOxCy films, which are deposited at lower RF power produce more leakage current, meanwhile the dielectric constant and refractive index of these films decreased mainly due to the more porosity in the film structure. By adding CF4 in the deposition process, fluorine, the most electronegative and the least polarized atom, doped into the silica film and led to decrease in the refractive index and the dielectric constant. In addition, no breakdown field was observed in the electrical characteristics of SiOxCyFz films and the leakage current of these films reduced by increment of the CF4 flow.
QsIA disrupts LasR dimerization in antiactivation of bacterial quorum sensing
Authors: Fan Hui , Dong Yihu , Wu Donghui , Bowler Matthew W. , Zhang Lianhui , Song Haiwei
Published: December 2013

Significance

Quorum sensing is a bacterial cell–cell communication system that is activated when the concentration of quorum sensing signal (autoinducer) reaches a threshold. In
Pseudomonas aeruginosa
, an opportunistic human pathogen, the quorum sensing threshold and response are defined by a novel antiactivator, QslA, which binds to the transcription factor LasR and prevents it from binding to its target DNA. However, how QslA binds to LasR and negatively regulates quorum sensing is poorly understood. Here we show that QsIA binds LasR to disrupt its dimerization, thereby inhibiting the DNA binding of LasR and shutting down transcription. Our findings reveal the molecular basis of a unique QsIA-mediated LasR inactivation and add an example to understand the antiactivation mechanism in bacterial quorum sensing.
How much can classifiers be analogous to their referents?
Authors: Sutton-Spence Rachel , Napoli Donna Jo
Published: December 2013

Sign Language poetry is especially valued for its presentation of strong visual images. Here, we explore the highly visual signs that British Sign Language and American Sign Language poets create as part of the ‘classifier system’ of their languages. Signed languages, as they create visually-motivated messages, utilise categoricity (more traditionally considered ‘language’) and analogy (more traditionally considered extra-linguistic and the domain of ‘gesture’). Classifiers in sign languages arguably show both these characteristics (Oviedo, 2004). In our discussion of sign language poetry, we see that poets take elements that are widely understood to be highly visual, closely representing their referents, and make them even more highly visual — so going beyond categorisation and into new areas of analogue.
Reconciling the effects of mutual visibility on gesturing
Authors: Bavelas Janet , Healing Sara
Published: December 2013

Fourteen visibility experiments, which compared the overall rate of gesturing when participants could or could not see each other, have produced perfectly contradictory results: Seven found a significantly higher overall gesture rate in the visible condition, and seven found no significant difference. Experiments that used quasi-dialogues in which the addressees’ responses were experimentally constrained (e.g., using a confederate) found a significant difference; the experiments that used free dialogues did not. This review examined three possible explanations and found that (1) the use of quasi-dialogues did not ensure better experimental control, (2) the constrained addressees may have introduced a confound that could account for the significant difference, and (3) although mutual visibility did not affect the overall gesture rate in free dialogues, it significantly increased more specific features of gestures that are useful to addressees. These findings raise several issues about the utility of conventional visibility designs for understanding conversational gestures.
Individual differences and usage-based grammar
Authors: Barlow Michael
Published: December 2013

Since usage-based theories such as cognitive grammar assume an intimate relationship between mental representations of grammar and the processing of instances of language (usage events), corpora have an important role in the development of grammatical analyses. One consequence of relying on corpus data is that individual differences in usage tend to be obscured. To overcome this problem and investigate individual differences in spoken usage, we examine a large corpus consisting of the spoken output of six White House press secretaries. The results provide strong evidence that within this one particular discourse context the patterns of speech of each individual are clearly recognisable. Furthermore, these idiolectal preferences are consistent and are maintained over a period of at least a year or two. In addition, we briefly explore some theoretical consequences and possible explanations for the disparity found between the speech of the individual and that of the discourse community.
Colloquial features in Word Englishes
Authors: Collins Peter , Yao Xinyue
Published: December 2013

A powerful discourse-pragmatic agent of grammatical change in English since the mid-twentieth century has been the increasing acceptance of colloquialism. Little is known, however, about its influence on grammatical developments in regional varieties of World English other than the two inner circle ‘supervarieties’, British and American English. This paper reports findings from a corpus-based study of three grammatical categories known to be undergoing a colloquialism-related rise in contemporary English, across a range of registers in ten World Englishes: quasi-modals (have to, have got to, be going to, want to), get-passives, and first person plural inclusive let’s. In each case comparisons are drawn with non-colloquial variants: modals (must, should, will, shall), be-passives, and let us. Subsequent functional interpretation of the data is used to explore the effect upon the quantitative patterns identified of the phenomenon of colloquialism and of further factors with which it interacts (including Americanism, prescriptivism, and evolutionary status).
A new computing method for extracting contiguous phraseological sequences from academic text corpora
Authors: Wei Naixing , Li Jingjie
Published: December 2013

This study aims to develop a new computing method for extracting contiguous phraseological sequences (PSs) of various lengths from academic text corpora by measuring internal associations of n-grams. We construct a new normalizing algorithm of probability-weighted average for refining the MI measure and enhancing precision in extracting PSs from corpora. This computing method is applied to the data in a medium-sized text corpus of academic English. Results indicate that the resultant new MI measure can provide statistics which better reveal internal associations within an n-gram, regardless of size. Lexico-grammatical sequences extracted with this method are more complete and less arbitrary in terms of grammar and semantics. The method can be applied to treating a variety of linguistic phenomenon, ranging from well-established phrases to likely phrasal entities, thus having potentially practical applications in corpus-based studies of phraseology and natural language processing.
‘Keywords Method’ versus ‘Calcul des Spécificités’
Authors: Bertels Ann , Speelman Dirk
Published: December 2013

This paper explores two tools and methods for keyword extraction. As several tools are available, it makes a comparison of two widely used tools, namely Lexico3 (Lamalle et al. 2003) and WordSmith Tools (Scott 2013). It shows the importance of keywords and discusses recent studies involving keyword extraction. Since no previous study has attempted to compare two different tools, used by different language communities and which use different methodologies to extract keywords, this paper aims at filling the gap by comparing not only the tools and their practical use, but also the underlying methodologies and statistics. By means of a comparative study on a small test corpus, this paper shows major similarities and differences between the tools. The similarities mainly concern the most typical keywords, whereas the differences concern the total number of significant keywords extracted, the granularity of both probability value and typicality coefficient and the type of the reference corpus.
La réciprocité dans les langues romanes anciennes
Authors: Nkollo Mikołaj
Published: December 2013

The paper traces evolutionary pathways of various methods of expressing reciprocity found in Old French (12th century) and Old Portuguese (13–15th century) texts. Most of grammaticalization patterns responsible for the emergence of reciprocal markers and documented in human languages are demonstrated to have been active in Old Romance, too. Medieval reciprocal exponents are first compared with their Latin ancestors to show what Romance innovations consisted in and what formal means were retained throughout. Then, an account is given of how the two languages were different from each other. Finally, two suggestions are made on how current grammaticalization theory can be modified so as to grasp more efficiently the origin of reciprocal markers found in European languages.
La copla andaluza y los poetas
Authors: García Miguel Ángel
Published: December 2013

From the so-called «fin de siglo» to the thirties some of the Spanish poets relied on the folk song –and more specifically on the «cante jondo» or flamenco– to define an alleged Andalusian soul. In opposition to the cheerful, colourful and folkloric Andalusia described by poets like Reina and Rueda, there are other Modernist authors like Villaespesa, Sánchez Rodríguez, Juan Ramón Jiménez or Darío who refined the literary image of Andalusia from the distinctive notes of sadness or grief, thus initiating a thematic chain which from the twenties extended Lorca’s image of «Andalucía del llanto» under Neopopularism and the Vanguard movement. This trend continued in the next decade, when Cansinos Assens and the Caba brothers placed similar emphasis on tragic Andalusia, based on an analysis of the «cante jondo» in which metaphysical, social and historical aspects were mixed. This paper aims to examine some of the key aspects of the relation between the sadness of the Andalusian song and Spanish poetry in the first third of the 20th century.
RNA-seq differential expression studies: more sequence or more replication?
Authors: Liu Yuwen , Zhou Jie , White Kevin P.
Published: December 2013

Motivation: RNA-seq is replacing microarrays as the primary tool for gene expression studies. Many RNA-seq studies have used insufficient biological replicates, resulting in low statistical power and inefficient use of sequencing resources.

Results: We show the explicit trade-off between more biological replicates and deeper sequencing in increasing power to detect differentially expressed (DE) genes. In the human cell line MCF7, adding more sequencing depth after 10 M reads gives diminishing returns on power to detect DE genes, whereas adding biological replicates improves power significantly regardless of sequencing depth. We also propose a cost-effectiveness metric for guiding the design of large-scale RNA-seq DE studies. Our analysis showed that sequencing less reads and performing more biological replication is an effective strategy to increase power and accuracy in large-scale differential expression RNA-seq studies, and provided new insights into efficient experiment design of RNA-seq studies.

Availability and implementation: The code used in this paper is provided on: http://home.uchicago.edu/∼jiezhou/replication/. The expression data is deposited in the Gene Expression Omnibus under the accession ID GSE51403.

Contact: kpwhite@uchicago.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
A phylogenetic Kalman filter for ancestral trait reconstruction using molecular data
Authors: Lartillot Nicolas
Published: December 2013

Motivation: Correlation between life history or ecological traits and genomic features such as nucleotide or amino acid composition can be used for reconstructing the evolutionary history of the traits of interest along phylogenies. Thus far, however, such ancestral reconstructions have been done using simple linear regression approaches that do not account for phylogenetic inertia. These reconstructions could instead be seen as a genuine comparative regression problem, such as formalized by classical generalized least-square comparative methods, in which the trait of interest and the molecular predictor are represented as correlated Brownian characters coevolving along the phylogeny.

Results: Here, a Bayesian sampler is introduced, representing an alternative and more efficient algorithmic solution to this comparative regression problem, compared with currently existing generalized least-square approaches. Technically, ancestral trait reconstruction based on a molecular predictor is shown to be formally equivalent to a phylogenetic Kalman filter problem, for which backward and forward recursions are developed and implemented in the context of a Markov chain Monte Carlo sampler. The comparative regression method results in more accurate reconstructions and a more faithful representation of uncertainty, compared with simple linear regression. Application to the reconstruction of the evolution of optimal growth temperature in Archaea, using GC composition in ribosomal RNA stems and amino acid composition of a sample of protein-coding genes, confirms previous findings, in particular, pointing to a hyperthermophilic ancestor for the kingdom.

Availability and implementation: The program is freely available at www.phylobayes.org.

Contact:  nicolas.lartillot@univ-lyon1.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Chemical structure informing statistical hypothesis testing in metabolomics
Authors: Zhu Hongjie , Luo Man
Published: December 2013

Motivation: Metabolomics has been shown as an effective tool to study various biological and biomedical phenotypes, whereas interrogating the inherently noisy metabolite concentration data with limited sample size remains a major challenge. Accumulating evidence suggests that metabolites’ structures are relevant to their bioactivities.

Results: We present a new strategy to boost the statistical power of hypothesis testing in metabolomics by incorporating quantitative molecular descriptors for each metabolite. The strategy selects potentially informative summary molecular descriptors and outputs chemical structure-informed false discovery rates. The effectiveness of the proposed strategy is demonstrated by both simulation studies and a real application. In a metabolomic study on Alzheimer’s disease, the posterior inclusion probability for summary molecular descriptors reaches 0.97. By incorporating the structure data, our approach uniquely identifies multiple Alzheimer’s disease signatures, which are consistent with existing evidence. These results evidently suggest the value of the proposed approach for metabolomic hypothesis-testing problems.

Availability and implementation: A code package implementing the strategy is freely available at https://github.com/HongjieZhu/CIMA.git.

Contact:  hongjie.zhu@sanofi.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection
Authors: Liu Bin , Zhang Deyuan , Xu Ruifeng , Xu Jinghao , Wang Xiaolong , Chen Qingcai , Dong Qiwen , Chou Kuo-Chen
Published: December 2013

Motivation: Owing to its importance in both basic research (such as molecular evolution and protein attribute prediction) and practical application (such as timely modeling the 3D structures of proteins targeted for drug development), protein remote homology detection has attracted a great deal of interest. It is intriguing to note that the profile-based approach is promising and holds high potential in this regard. To further improve protein remote homology detection, a key step is how to find an optimal means to extract the evolutionary information into the profiles.

Results: Here, we propose a novel approach, the so-called profile-based protein representation, to extract the evolutionary information via the frequency profiles. The latter can be calculated from the multiple sequence alignments generated by PSI-BLAST. Three top performing sequence-based kernels (SVM-Ngram, SVM-pairwise and SVM-LA) were combined with the profile-based protein representation. Various tests were conducted on a SCOP benchmark dataset that contains 54 families and 23 superfamilies. The results showed that the new approach is promising, and can obviously improve the performance of the three kernels. Furthermore, our approach can also provide useful insights for studying the features of proteins in various families. It has not escaped our notice that the current approach can be easily combined with the existing sequence-based methods so as to improve their performance as well.

Availability and implementation: For users’ convenience, the source code of generating the profile-based proteins and the multiple kernel learning was also provided at

http://bioinformatics.hitsz.edu.cn/main/∼binliu/remote/

Contact:  bliu@insun.hit.edu.cn or bliu@gordonlifescience.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
Hyperactive mariner transposons are created by mutations that disrupt allosterism and increase the rate of transposon end synapsis
Authors: Liu Danxu , Chalmers Ronald
Published: December 2013

New applications for transposons in vertebrate genetics have spurred efforts to develop hyperactive variants. Typically, a genetic screen is used to identify several hyperactive point mutations, which are then incorporated in a single transposase gene. However, the mechanisms responsible for the increased activity are unknown. Here we show that several point mutations in the mariner transposase increase their activities by disrupting the allostery that normally serves to downregulate transposition by slowing synapsis of the transposon ends. We focused on the conserved WVPHEL amino acid motif, which forms part of the mariner transposase dimer interface. We generated almost all possible single substitutions of the W, V, E and L residues and found that the majority are hyperactive. Biochemical analysis of the mutations revealed that they disrupt signals that pass between opposite sides of the developing transpososome in response to transposon end binding. In addition to their role in allostery, the signals control the initiation of catalysis, thereby preventing non-productive double-strand breaks. Finally, we note that such breaks may explain the puzzling ‘self-inflicted wounds’ at the ends of the Mos1 transposon in Drosophila.
A cypovirus VP5 displays the RNA chaperone-like activity that destabilizes RNA helices and accelerates strand annealing
Authors: Yang Jie , Cheng Zhenyun , Zhang Songliu , Xiong Wei , Xia Hongjie , Qiu Yang , Wang Zhaowei , Wu Feige , Qin Cheng-Feng , Yin Lei , Hu Yuanyang , Zhou Xi
Published: December 2013

For double-stranded RNA (dsRNA) viruses in the family Reoviridae, their inner capsids function as the machinery for viral RNA (vRNA) replication. Unlike other multishelled reoviruses, cypovirus has a single-layered capsid, thereby representing a simplified model for studying vRNA replication of reoviruses. VP5 is one of the three major cypovirus capsid proteins and functions as a clamp protein to stabilize cypovirus capsid. Here, we expressed VP5 from type 5 Helicoverpa armigera cypovirus (HaCPV-5) in a eukaryotic system and determined that this VP5 possesses RNA chaperone-like activity, which destabilizes RNA helices and accelerates strand annealing independent of ATP. Our further characterization of VP5 revealed that its helix-destabilizing activity is RNA specific, lacks directionality and could be inhibited by divalent ions, such as Mg2+, Mn2+, Ca2+ or Zn2+, to varying degrees. Furthermore, we found that HaCPV-5 VP5 facilitates the replication initiation of an alternative polymerase (i.e. reverse transcriptase) through a panhandle-structured RNA template, which mimics the 5′-3′ cyclization of cypoviral positive-stranded RNA. Given that the replication of negative-stranded vRNA on the positive-stranded vRNA template necessitates the dissociation of the 5′-3′ panhandle, the RNA chaperone activity of VP5 may play a direct role in the initiation of reoviral dsRNA synthesis.
Expanding the catalog of cas genes with metagenomes
Authors: Zhang Quan , Doak Thomas G. , Ye Yuzhen
Published: December 2013

The CRISPR (clusters of regularly interspaced short palindromic repeats)–Cas adaptive immune system is an important defense system in bacteria, providing targeted defense against invasions of foreign nucleic acids. CRISPR–Cas systems consist of CRISPR loci and cas (CRISPR-associated) genes: sequence segments of invaders are incorporated into host genomes at CRISPR loci to generate specificity, while adjacent cas genes encode proteins that mediate the defense process. We pursued an integrated approach to identifying putative cas genes from genomes and metagenomes, combining similarity searches with genomic neighborhood analysis. Application of our approach to bacterial genomes and human microbiome datasets allowed us to significantly expand the collection of cas genes: the sequence space of the Cas9 family, the key player in the recently engineered RNA-guided platforms for genome editing in eukaryotes, is expanded by at least two-fold with metagenomic datasets. We found genes in cas loci encoding other functions, for example, toxins and antitoxins, confirming the recently discovered potential of coupling between adaptive immunity and the dormancy/suicide systems. We further identified 24 novel Cas families; one novel family contains 20 proteins, all identified from the human microbiome datasets, illustrating the importance of metagenomics projects in expanding the diversity of cas genes.
Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing
Authors: Paliwal Shreya , Kanagaraj Radhakrishnan , Sturzenegger Andreas , Burdova Kamila , Janscak Pavel
Published: December 2013

Most mitotic homologous recombination (HR) events proceed via a synthesis-dependent strand annealing mechanism to avoid crossing over, which may give rise to chromosomal rearrangements and loss of heterozygosity. The molecular mechanisms controlling HR sub-pathway choice are poorly understood. Here, we show that human RECQ5, a DNA helicase that can disrupt RAD51 nucleoprotein filaments, promotes formation of non-crossover products during DNA double-strand break-induced HR and counteracts the inhibitory effect of RAD51 on RAD52-mediated DNA annealing in vitro and in vivo. Moreover, we demonstrate that RECQ5 deficiency is associated with an increased occupancy of RAD51 at a double-strand break site, and it also causes an elevation of sister chromatid exchanges on inactivation of the Holliday junction dissolution pathway or on induction of a high load of DNA damage in the cell. Collectively, our findings suggest that RECQ5 acts during the post-synaptic phase of synthesis-dependent strand annealing to prevent formation of aberrant RAD51 filaments on the extended invading strand, thus limiting its channeling into potentially hazardous crossover pathway of HR.
Anti-HIV-1 activity of Trim 37
Authors: Tabah Azah A. , Tardif Keith , Mansky Louis M.
Published: December 2013

Trim 5α was the first member of the tripartite motif (TRIM) family of proteins that was identified to potently restrict human immunodeficiency virus type 1 (HIV-1) replication. The breadth of antiretroviral activity of TRIM family members is an active area of investigation. In this study, we demonstrate that human Trim 37 possesses anti-HIV-1 activity. This antiretroviral activity and the manner in which it was displayed were implicated by (1) decreased viral replication upon Trim 37 transient overexpression in virus-producing cells, (2) correlation of the reduction of viral infectivity with Trim 37 virion incorporation, (3) increased HIV-1 replication during siRNA depletion of Trim 37 expression, and (4) reduction in viral DNA synthesis upon Trim 37 transient overexpression. Our findings provide the first demonstration, to our knowledge, of the potent antiviral activity of human Trim 37, and implicate an antiviral mechanism whereby Trim 37 interferes with viral DNA synthesis.
Evolution at two levels of gene expression in yeast
Authors: Artieri Carlo G. , Fraser Hunter B.
Published: December 2013

Despite the greater functional importance of protein levels, our knowledge of gene expression evolution is based almost entirely on studies of mRNA levels. In contrast, our understanding of how translational regulation evolves has lagged far behind. Here we have applied ribosome profiling—which measures both global mRNA levels and their translation rates—to two species ofSaccharomycesyeast and their interspecific hybrid in order to assess the relative contributions of changes in mRNA abundance and translation to regulatory evolution. We report that bothcis-andtrans-acting regulatory divergence in translation are abundant, affecting at least 35% of genes. The majority of translational divergence acts to buffer changes in mRNA abundance, suggesting a widespread role for stabilizing selection acting across regulatory levels. Nevertheless, we observe evidence of lineage-specific selection acting on several yeast functional modules, including instances of reinforcing selection acting at both levels of regulation. Finally, we also uncover multiple instances of stop-codon readthrough that are conserved between species. Our analysis reveals the underappreciated complexity of post-transcriptional regulatory divergence and indicates that partitioning the search for the locus of selection into the binary categories of “coding” versus “regulatory” may overlook a significant source of selection, acting at multiple regulatory levels along the path from genotype to phenotype.
Greater trochanteric pain syndrome: Does imaging‐identified pathology influence the outcome of interventions?
Authors: Wilson Shayne A. , Shanahan Ernst M. , Smith Malcolm D.
Published: December 2013

Aim

To assess the outcomes for patients seen in a rheumatology service presenting with features of the greater trochanteric pain syndrome (GTPS) and the impact of imaging results on the outcomes of treatment.

Methods

Retrospective audit, using a phone interview was performed to establish links between results of imaging undertaken in the diagnostic work‐up of patients with lateral hip pain and clinical outcomes for these patients. Patient perceptions of the effectiveness of interventions were also assessed.

Results

Forty‐five patients were included (82% female, mean age 69.6 years). Sixty‐nine percent underwent radiological work‐up, including plain X‐rays (55%), computed tomography scans (64%), magnetic resonance imaging (48%) and ultrasound (90%). Coexistent trochanteric bursitis (TB) and gluteal tendinopathy were the most commonly elucidated pathologies accounting for the symptomatic presentation of 40% of patients. Forty‐one patients underwent some form of intervention, most commonly injection of local anesthetic and corticosteroid (LACS) into the region of the TB (87%), two‐thirds of which were undertaken under radiological guidance. Pain reduction was maximal following the third injection, with a significantly better response to unguided interventions and levels of symptomatic relief following the first injection being a good indicator of the probability of complete remission. Radiological demonstration of isolated TB correlated with a greater reduction in lateral hip symptoms following LACS TB injections both in the immediate post‐injection phase and in the long‐term.

Conclusion

The results of this audit suggest that the management of GTPS has reasonable patient outcomes; however, a prospective study with greater patient numbers is needed to confirm these results.
Phenotype and Functionality of CD4+ and CD8+ T Cells in the Upper Reproductive Tract of Healthy Premenopausal Women
Authors: Shanmugasundaram Uma , Critchfield J. William , Pannell Jane , Perry Jean , Giudice Linda C. , Smith‐McCune Karen , Greenblatt Ruth M. , Shacklett Barbara L.
Published: December 2013

Problem

The goal of this study was to investigate the phenotype and functional responsiveness of CD4+ and CD8+ T‐cells in the upper reproductive tract of healthy premenopausal women. The lower reproductive tract is frequently studied as a site of sexually transmitted infections; however, the upper reproductive tract may also be a portal of entry and dissemination for pathogens, including HIV‐1.

Method of Study

Endometrial biopsy, endocervical curettage, cytobrush, and blood were collected during mid‐luteal phase from 23 healthy women. T‐cells were isolated and analyzed by flow cytometry.

Results

As compared with their counterparts in blood, endometrial and endocervical T‐cells had enhanced CCR5 expression, and were enriched for activated, effector memory cells. Endometrial T‐cells were more responsive to polyclonal stimuli, producing a broad range of cytokines and chemokines.

Conclusion

These findings underscore the responsiveness of endometrial T‐cells to stimulation, and reveal their activated phenotype. These findings also suggest susceptibility of the upper reproductive tract to HIV‐1 infection.
Addiction‐Related Effects of DOV 216,303 and Cocaine: A Comparative Study in the Mouse
Authors: Sørensen Gunnar , Husum Henriette , Brennum Lise T. , Bundgaard Christoffer , Montezinho Liliana C. P. , Mørk Arne , Wörtwein Gitta , Woldbye David P. D.
Published: December 2013

DOV 216,303, an inhibitor of serotonin, noradrenaline and dopamine reuptake, belongs to a new line of drugs called ‘triple reuptake inhibitors’ that have been proposed for treatment of depression. The addictive drug cocaine has similar mechanism of action and exerts rewarding effects by blocking reuptake of dopamine, leading to increased extracellular concentrations of dopamine in the nucleus accumbens. Thus, DOV 216,303 and other triple reuptake inhibitors might be speculated to exhibit abuse potential, limiting their future therapeutic use. To further elucidate potential addictive properties of DOV 216,303, we conducted a comparative study of addiction‐related effects of DOV 216,303 and cocaine in mice using acute self‐administration, conditioned place preference (CPP) and drug‐induced hyperlocomotion. Effects on accumbal extracellular dopamine levels were determined using microdialysis, and we measured monoamine receptor occupancy as well as brain and plasma exposure. DOV 216,303 was self‐administered acutely in the same dose range as cocaine. However, in the CPP model, DOV 216,303 did not induce place preference at doses where cocaine caused place preference. Higher doses of DOV 216,303 than cocaine were needed to induce hyperlocomotion and increase extracellular accumbal dopamine with effective doses being higher than effective doses used in depression models. Moreover, DOV 216,303 displayed a pharmacokinetic profile with lower potential for addiction than cocaine. Thus, high levels of DAT occupancy were reached slower and decayed more slowly after DOV 216,303 than cocaine administration. The present study shows that acute administration of DOV 216,303 displays some addictive‐like properties in mice, but these were less pronounced than cocaine, most likely due to different pharmacokinetic profiles.
IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients
Authors: Kato Fumiko , Hamajima Takashi , Hasegawa Tomonobu , Amano Naoko , Horikawa Reiko , Nishimura Gen , Nakashima Shinichi , Fuke Tomoko , Sano Shinichirou , Fukami Maki , Ogata Tsutomu
Published: December 2013

Objective

Arboleda et al. have recently shown that IMAGe (intra‐uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome is caused by gain‐of‐function mutations of maternally expressed gene CDKN1C on chromosome 11p15.5. However, there is no other report describing clinical findings in patients with molecularly studied IMAGe syndrome. Here, we report clinical and molecular findings in Japanese patients.

Patients

We studied a 46,XX patient aged 8·5 years (case 1) and two 46,XY patients aged 16·5 and 15·0 years (cases 2 and 3).

Results

Clinical studies revealed not only IMAGe syndrome‐compatible phenotypes in cases 1–3, but also hitherto undescribed findings including relative macrocephaly and apparently normal pituitary‐gonadal endocrine function in cases 1–3, familial glucocorticoid deficiency (FGD)‐like adrenal phenotype and the history of oligohydramnios in case 2, and arachnodactyly in case 3. Sequence analysis of CDKN1C, pyrosequencing‐based methylation analysis of KvDMR1 and high‐density oligonucleotide array comparative genome hybridization analysis for chromosome 11p15.5 were performed, showing an identical de novo and maternally inherited CDKN1C gain‐of‐function mutation (p.Asp274Asn) in cases 1 and 2, respectively, and no demonstrable abnormality in case 3.

Conclusions

The results of cases 1 and 2 with CDKN1C mutation would argue the following: [1] relative macrocephaly is consistent with maternal expression of CDKN1C in most tissues and biparental expression of CDKN1C in the foetal brain; [2] FGD‐like phenotype can result from CDKN1C mutation; and [3] genital abnormalities may primarily be ascribed to placental dysfunction. Furthermore, lack of CDKN1C mutation in case 3 implies genetic heterogeneity in IMAGe syndrome.
“Raised Eyebrows”: Working with Lesbian‐Parented Families — Experiences of Childcare Centre Directors in Australia
Authors: Cloughessy Kathy , Waniganayake Manjula
Published: December 2013

When reflecting on their experiences with children from lesbian‐parented families, 64 childcare centre directors in Victoria, Australia indicated that explicit programs, policies or resources of support were absent in their centres. Importantly, participants' pre‐ and post‐professional education either ignored or superficially addressed lesbian matters. This may explain the limited nature of inclusion of lesbian matters in early childhood education. Of note, is the pervasive nature of ‘truths’ upheld by educators. That is, in the Foucauldian sense these educators perceived lesbian families as being the ‘same’ as heterosexual families. Despite the considerable shifts in professional attitudes and ‘truths’ about sexuality, the Foucauldian silences were being reinforced in everyday practice as evidenced by the reference to ‘raised eyebrows’ by participants when this silence about sexuality was threatened.
Conservative management, surgery and radiosurgery for treatment of vestibular schwannomas: a model‐based approach to cost‐effectiveness
Authors: Gait C. , Frew E.J. , Martin T.P.C. , Jowett S. , Irving R.
Published: December 2013

Objective

To undertake a cost‐effectiveness analysis comparing conservative management, surgery and radiosurgery for treating small‐to‐medium (1–20 mm)‐sized vestibular schwannomas.

Design

Model‐based economic evaluation using individual‐level data from a Birmingham‐based longitudinal patient database and from published sources. Both a decision tree and state‐transition (Markov) model were developed, from an National Health Service (NHS) perspective. Sensitivity analyses were also carried out.

Setting

Secondary care treatment for patients with small‐to‐medium‐sized vestibular schwannomas.

Participants

Three hypothetical cohorts of adult patients receiving conservative management, radiosurgery or surgery treatment, aged 58 years as starting age within model.

Main outcome measures

Cost‐effectiveness based on cost per quality‐adjusted life year (QALY).

Results

Conservative management is the preferred strategy for the treatment of small‐to‐medium‐sized vestibular schwannomas. Conservative management is both cheaper (−£722 and −£2764) and more effective (0.136 and 0.554 quality‐adjusted life years) than both radiosurgery and surgery, respectively. A conservative strategy can therefore be considered as highly cost‐effective. This result is sensitive to the assumed quality‐of‐life parameters in the model. Sensitivity analysis suggests that the probability of a conservative strategy being the most cost‐effective approach compared with surgery and radiosurgery at a willingness to pay of £20 000/quality‐adjusted life year gained is 80% and 55%, respectively.

Conclusions

A conservative approach is the preferred strategy for treatment of small‐to‐medium vestibular schwannomas. This result is sensitive to quality‐of‐life values used in the analysis. More research is required to assess the impact of treatment upon patients’ health‐related quality of life over time.
Crawling and walking infants elicit different verbal responses from mothers
Authors: Karasik Lana B. , Tamis‐LeMonda Catherine S. , Adolph Karen E.
Published: December 2013

We examined mothers' verbal responses to their crawling or walking infants' object sharing (i.e. bids). Fifty mothers and their 13‐month‐olds were observed for 1 hour at home. Infants bid from a stationary position or they bid after carrying the object to their mothers. Mothers responded with affirmations (e.g. ‘thank you’), descriptions (‘red box’), or action directives (‘open it’). Infants' locomotor status and the form of their bids predicted how mothers responded. Mothers of walkers responded with action directives more often than mothers of crawlers. Notably, differences in the responses of mothers of walkers versus those of crawlers were explained by differences in bid form between the two groups of infants. Walkers were more likely to engage in moving bids than crawlers, who typically shared objects from stationary positions. When crawlers displayed moving bids, their mothers offered action directives just as often as did mothers of walkers. Findings illustrate developmental cascades, wherein Infants' locomotor status affects how infants share objects with mothers, which in turn shapes mothers' verbal responses.
Pancreas transplantation: a treatment option for people with diabetes
Authors: Mittal S. , Gough S. C. L.
Published: December 2013

Since the first pancreas transplants in the early 1960s, whole‐organ pancreas transplantation, either alone or combined with kidney transplantation, has become commonplace in many countries around the world. Whole‐organ pancreas transplantation is available in the UK, with ~200 transplants currently carried out per year. Patient survival and pancreas graft outcome rates are now similar to other solid organ transplant programmes, with high rates of long‐term insulin independence. In the present review, we will discuss whole‐pancreas transplantation as a treatment for diabetes, focusing on indications for transplantation, the nature of the procedure performed, graft survival rates and the consequences of pancreas transplantation on metabolic variables and the progression of diabetes‐related complications.
Using an audience response system to improve learning success in practical skills training courses in dental studies – a randomised, controlled cross‐over study
Authors: Wenz H.‐J. , Zupanic M. , Klosa K. , Schneider B. , Karsten G.
Published: December 2013

Introduction

The aim of this study was to examine whether the use of an audience response system (ARS) in a high‐quality study design, in a course in pre‐clinical dentistry leads to an improvement in cognitive and psycho‐motor performance.

Materials and Methods

As part of the Phantom Course I, a randomised, controlled study in cross‐over design with 63 students was conducted over 4 weeks. The intervention was carried out by means of an ARS (TurningPoint®), while a verbal question‐and‐answer session was conducted within the control group. Differences in learning success were determined via a formative multiple‐choice (MC) test (cognitive) and a summative practical test (psycho‐motor).

Results

Both groups achieved significantly better results in the MC tests with the use of the intervention, when compared with the control group (group A 11.6 vs. 9.5 and group B 13.7 vs. 12.1, maximum 16 points). A further analysis of the results showed that the overall effect was induced primarily by a marked improvement in below‐average students. The practical tests showed no clear effect. Despite the careful selection and set‐up of the conditions for the study in the regular course of the semester, a cohort effect emerged. This was due to varying degrees of performance between the two groups, because no adequate performance parameters were available, which could have been taken into account for the stratified randomisation.

Conclusions

The results indicate that the use of the ARS leads to better results in cognitive performance, especially where independent learning is required and should be encouraged. Weaker students in particular seem to benefit.
Hemodynamic effect of external counterpulsation is a different measure of impaired cerebral autoregulation from vasoreactivity to breath‐holding
Authors: Lin W. , Xiong L. , Han J. , Leung T. , Leung H. , Chen X. , Wong K. S. L.
Published: December 2013

Background and purpose

External counterpulsation (ECP) is a novel method to increase cerebral blood flow, which may benefit acute ischaemic stroke patients. Our aim was to identify whether the hemodynamic effect of ECP is associated with cerebral vasoreactivity to breath‐holding.

Methods

Thirty‐seven recent ischaemic stroke patients with large artery steno‐occlusive disease were recruited together with 20 healthy controls. All underwent ECP treatment and a breath‐holding test combined with transcranial Doppler monitoring on bilateral middle cerebral arteries was performed. The data of the stroke patients were designated as ipsilateral or contralateral based on the side of the infarct, whilst the average of both sides was used in controls. The cerebral augmentation index (CAI) was used to evaluate the augmentation effects of ECP. Cerebral vasoreactivity was assessed by using the breath‐holding index (BHI).

Results

Middle cerebral artery mean flow velocities significantly increased in the stroke group after ECP but not in controls. BHIs were much smaller in the stroke group than in the controls. The CAI did not correlate with the BHI in either the ipsilateral or contralateral side of the stroke group or in controls. For stroke patients, BHI was significantly lower on the ipsilateral side than the contralateral side, but the CAI showed no difference between the two cerebral hemisphere sides. The CAI of stroke patients was significantly related to mean blood pressure change on the ipsilateral side.

Conclusion

The dynamic augmentation effects of ECP as measured by the CAI were different from the well established vasoreactivity to breath‐holding. The CAI is suggested as a measure of how well the brain accommodates blood flow augmentation during ECP.
Genetic assessment of familial and early‐onset Parkinson's disease in a Greek population
Authors: Bozi M. , Papadimitriou D. , Antonellou R. , Moraitou M. , Maniati M. , Vassilatis D. K. , Papageorgiou S. G. , Leonardos A. , Tagaris G. , Malamis G. , Theofilopoulos D. , Kamakari S. , Stamboulis E. , Hadjigeorgiou G. M. , Athanassiadou A. , Michelakakis H. , Papadimitriou A. , Gasser T. , Stefanis L.
Published: December 2013

Background and purpose

Although the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha‐synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population.

Methods

A genetic analysis in 111 familial or sporadic with early‐onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ‐1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene.

Results

In total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations.

Conclusions

The A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.
Hepatitis C viral infection and the risk of dementia
Authors: Chiu W.‐C. , Tsan Y.‐T. , Tsai S.‐L. , Chang C.‐J. , Wang J.‐D. , Chen P.‐C. ,   Health Data Analysis in Taiwan (hDATa) Research Group
Published: December 2013

Background and purpose

Hepatitis C virus (HCV) infection may cause cognitive impairment, but no studies have focused specifically on cognitive impairment stemming from HCV. The purpose of this study was to investigate the potential increased risk for dementia in HCV‐infected patients.

Methods

A population‐based cohort study based on the Taiwan National Health Insurance Research Database was conducted. From all potential participants aged 50 years or more, a total of 58 570 matched (1:1) pairs of HCV‐infected patients and non‐HCV‐infected patients were included. Each subject was individually tracked from 1997 to 2009 to identify incident cases of dementia (onset in 1999 or later). Cox proportional hazards regressions were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HCV infection and dementia.

Results

There were 2989 dementia cases from the HCV‐infected cohort during the follow‐up period of 533 861.1 person‐years; the overall incidence rates of dementia differed from the non‐HCV cohort (56.0 vs. 47.7 cases per 10 000 person‐years, P < 0.05). The adjusted HR for dementia was 1.36 (95% CI 1.27–1.42) for HCV‐infected patients after adjusting for alcohol‐related disease, liver cirrhosis, hepatic encephalopathy and hepatocellular carcinoma.

Conclusions

HCV infection may increase the risk for dementia. Further mechanistic research is needed.