bluuebunny/crossref_metadata_2025 huggingface dataset:
Limits of nationalist mobilization: Bromberg/Bydgoszcz in theKaiserreich,1900–1918
Authors: Spickermann Roland
Published: November 2011

Discussions about ethnic mobilization in eastern Europe have emphasized efforts of nationalist leaders to demarcate their community from their neighbors in mixed areas where ethnic boundaries and identities were blurred. Demarcation became a common means of defining the community both geographically and culturally, a process which later facilitated the community's mobilization. In the German Empire, however, the Polish-German demarcation was already stark, since it mostly coincided with Catholic-Protestant demarcations. But while the Polish community mobilized quickly and showed great solidarity, the German community did not. Using the Bromberg/Bydgoszcz administrative district as a model, the article argues that the local German community's internal divisions limited its ability to mobilize. Germans agreed on the need for greater German community solidarity, but differed on conceptualizations of its ideal structure and form. Liberal nationalists, envisioning a more egalitarian community defined by a common ethnicity, fought with local conservatives, who were as intent on preserving their prominence within the community as they were on struggling with the Poles. Such divisions crippled local German mobilization on any scale comparable to their Polish neighbors, suggesting that an ethnic community's self-demarcation is necessary but not sufficient to ensure its mobilization.
Participant development in sport and physical activity: The impact of biological maturation
Authors: Ford Paul , Collins Dave , Bailey Richard , MacNamara Áine , Pearce Gemma , Toms Martin
Published: November 2011

Recent literature sees participation in sport and physical activity as a lifelong continuum. As a consequence, youth sport must be seen as more than just about young athletes achieving elite performance. Accordingly, there is a need to improve our understanding of development in order to help grow and maintain involvement in sport and physical activity since the spectrum of participation is linked on a bio‐psycho‐social perspective throughout life. Reflecting this need, the paper reviews the evidence underpinning various ‘accepted constructs’ of development such as non‐linear biological growth, specialised physical development periods, and the associated acute and chronic training prescription implications. Based on such, the paper identifies a need for academics and practitioners to work more closely to establish an evidence‐base related to accelerated and decelerated periods of athletic development during maturation using controlled longitudinal investigations in order to help nurture athletic development and participation pathways from a lifelong perspective to a greater extent.
Hyperinsulinemia and overweight in obese Zucker rats effectively suppressed by exercise training with hypoxia recovery
Authors: Wu Ming‐Chieh , Tsai Ying‐Lan , Huang Chih‐Yang , Kao Chung‐Lan , Hou Chien‐Wen , Chen Chung‐Yu , Korivi Mallikarjuna , Jean Wei‐Horng , Lee Shin‐Da , Kuo Chia‐Hua
Published: November 2011

It is currently unknown whether hypoxia training can effectively suppress overweight and hyperinsulinemia in genetically obese animals. In this study, both lean and obese Zucker rats were randomly assigned into the following groups: control (CON, n=7), exercise training (EX, n=7), hypoxia (HYP, n=7) and exercise training with hypoxia recovery (EX+HYP, n=7). During a 6‐week training period, rats performed swimming exercise progressively from 30 to 180 min·day−1, and recovered under hypoxia (14% oxygen for 8 h·day−1). Obese Zucker rats exhibited substantially greater fasting insulin levels, and exaggerated glucose and insulin responses following an oral glucose challenge compared with lean rats. At the beginning of week 6, body weight, fasting glucose, fasting insulin, area under curve of glucose (GAUC) and insulin (IAUC) in the EX+HYP group were significantly lower than CON group among the obese rats. Meanwhile, only GAUC was significantly lower in the EX group compared to the CON group. At the end of week 6, capillaries to fibre ratio (C/F), capillary density (CD) and type IIa fibre proportion of the plantaris muscle in the EX group were significantly greater than the CON group (P<0.05), but no additive effect of hypoxia on exercise training was observed. Our data demonstrate that exercise training with prolonged hypoxia recovery offers better metabolic benefits than exercise training alone for the obese Zucker rats. This advantage was closely associated with effective weight reduction.
High Resolution Crossed Molecular Beams Study on the F+HD→HF+D Reaction at Collision Energy of 5.43–18.73 kJ/mol
Authors: Dong Wen-rui , Xiao Chun-lei , Wang Tao , Dai Dong-xu , Wang Xiu-yan , Yang Xue-ming
Published: November 2011

The dynamics of F+HD→HF+D reaction has been studied at ten collision energies ranging from 5.43 kJ/mol to 18.73 kJ/mol using high-resolution H/D atom Rydberg tagging time-of-flight method. Product vibrational and rotational state-resolved differential cross sections have been determined. The intensity of the HF(v′ = 2) forward products decreases as the collision energy increases, suggesting that the resonance contribution is reduced as the collision energy increases. The forward peak of HF(v′=3) product has also been observed above the threshold of this product channel. Product energy disposals in different degrees of freedom have been analyzed. The collision energy dependence of the HF vibrational product branching was also determined. This work presents a comprehensive dynamic picture of this resonance mediated reaction in a wide collision energy regime, providing a good test ground for theoretical understandings of this interesting reaction at higher collision energies.
Temperature-Dependence of the Amide-I Frequency Map for Peptides and Proteins
Authors: Han Chen , Wang Jian-ping
Published: November 2011

In our recent work [Phys. Chem. Chem. Phys. 11, 9149 (2009)], a molecular-mechanics force field-based amide-I vibration frequency map (MM-map) for peptides and proteins was constructed. In this work, the temperature dependence of the MM-map is examined based on high-temperature molecular dynamics simulations and infrared (IR) experiments. It is shown that the 298-K map works for up to 500-K molecular dynamics trajectories, which reasonably reproduces the 88°C experimental IR results. Linear IR spectra are also simulated for two tripeptides containing natural and unnatural amino acid residues, and the results are in reasonable agreement with experiment. The results suggest the MM-map can be used to obtain the temperature-dependent amide-I local mode frequencies and their distributions for peptide oligomers, which is useful in particular for understanding the IR signatures of the thermally unfolded species.
Photodissociation and Density Functional Calculations of Small VmOn+ Clusters
Authors: Li Ren-zhong , Xu Hong-guang , Cao Guo-jin , Zhao Yu-chao , Zheng Wei-jun
Published: November 2011

Oxygen-poor vanadium oxide clusters, V2On+ (n = 1, 2), V3On+ (n = 1, 2, 3), and V4O3+, were produced by laser vaporization and were mass-selected and photodissociated with 532 and 266 nm photons. The geometric structures and possible dissociation channels of these clusters were determined based on the comparison of density functional calculations and photodissociation experiments. The experiments show that the dissociation of V2O+, V2O2+, and V3O3+ mainly occurs by loss of VO, while the dissociation of V3O+ and V4O3+ mainly occurs by loss of V atom. For the dissociation of V3O2+, the VO loss channel is slightly dominant compared to the V loss channel. The combination of experimental results and theoretical calculations suggests that the V loss channels of V3O+ and V4O3+ are single photon processes at both 532 and 266 nm. The VO loss channels of V2O2+ and V3O3+ are multiple-photon processes at both 532 and 266 nm.
Photochemical Hydrogen Abstraction and Electron Transfer Reactions of Tetrachlorobenzoquinone with Pyrimidine Nucleobases
Authors: Liu Kun-hui , Wu Li-dan , Zou Xiao-ran , Yang Wen , Du Qian , Su Hong-mei
Published: November 2011

Pentachlorophenol, a widespread environmental pollutant that is possibly carcinogenic to humans, is metabolically oxidized to tetrachloroquinone (TCBQ) which can result in DNA damage. We have investigated the photochemical reaction dynamics of TCBQ with two pyrimidine type nucleobases (thymine and uracil) upon UVA (355 nm) excitation using the technique of nanosecond time-resolved laser flash photolysis. It has been found that 355 nm excitation populates TCBQ molecules to their triplet state 3TCBQ*, which are highly reactive towards thymine or uracil and undergo two parallel reactions, the hydrogen abstraction and electron transfer, leading to the observed photoproducts of TCBQH· and TCBQ·− in transient absorption spectra. The concomitantly produced nucleobase radicals and radical cations are expected to induce a series of oxidative or strand cleavage damage to DNA afterwards. By characterizing the photochemical hydrogen abstraction and electron transfer reactions, our results provide potentially important molecular reaction mechanisms for understanding the carcinogenic effects of pentachlorophenol and its metabolites TCBQ.
Protein Conformational Change Based on a Two-dimensional Generalized Langevin Equation
Authors: Wang Ying-xi , Linguang Shuang-mu , Zhao Nan-rong , Yan Yi-jing
Published: November 2011

A two-dimensional generalized Langevin equation is proposed to describe the protein conformational change, compatible to the electron transfer process governed by atomic packing density model. We assume a fractional Gaussian noise and a white noise through bond and through space coordinates respectively, and introduce the coupling effect coming from both fluctuations and equilibrium variances. The general expressions for autocorrelation functions of distance fluctuation and fluorescence lifetime variation are derived, based on which the exact conformational change dynamics can be evaluated with the aid of numerical Laplace inversion technique. We explicitly elaborate the short time and long time approximations. The relationship between the two-dimensional description and the one-dimensional theory is also discussed.
Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression inCandida albicans
Authors: Senn Heather , Shapiro Rebecca S. , Cowen Leah E.
Published: November 2011

The trimorphic fungus Candida albicans is the leading cause of systemic candidiasis, a disease with poor prognosis affecting immunocompromised individuals. The capacity of C. albicans to transition between morphological states is a key determinant of its ability to cause life-threatening infection. Recently the molecular chaperone heat shock protein 90 (Hsp90) was implicated as a major regulator of temperature-dependent C. albicans morphogenesis; compromising Hsp90 function induces filamentation and relieves repression of Ras1–protein kinase A (PKA) signaling, although the mechanism involved remains unknown. Here we demonstrate that filaments generated by compromise of Hsp90 function are neither pseudohyphae nor hyphae but closely resemble filaments formed in response to cell cycle arrest. Closer examination revealed that these filaments exhibit a delay in mitotic exit mediated by the checkpoint protein Bub2. Furthermore, Hsp90 inhibition also led to a distinct morphology with defects in cytokinesis. We found that the cyclin-dependent kinase Cdc28 was destabilized in response to depletion of Hsp90 and that Cdc28 physically interacts with Hsp90, implicating this major cell cycle regulator as a novel Hsp90 client protein in C. albicans. Taken together, our results suggest that Hsp90 is instrumental in the regulation of cell division during yeast-form growth in C. albicans and exerts its major effects during late cell cycle events.
QuRe: software for viral quasispecies reconstruction from next-generation sequencing data
Authors: Prosperi Mattia C. F. , Salemi Marco
Published: November 2011

Summary: Next-generation sequencing (NGS) is an ideal framework for the characterization of highly variable pathogens, with a deep resolution able to capture minority variants. However, the reconstruction of all variants of a viral population infecting a host is a challenging task for genome regions larger than the average NGS read length. QuRe is a program for viral quasispecies reconstruction, specifically developed to analyze long read (>100 bp) NGS data. The software performs alignments of sequence fragments against a reference genome, finds an optimal division of the genome into sliding windows based on coverage and diversity and attempts to reconstruct all the individual sequences of the viral quasispecies—along with their prevalence—using a heuristic algorithm, which matches multinomial distributions of distinct viral variants overlapping across the genome division. QuRe comes with a built-in Poisson error correction method and a post-reconstruction probabilistic clustering, both parameterized on given error rates in homopolymeric and non-homopolymeric regions.

Availability: QuRe is platform-independent, multi-threaded software implemented in Java. It is distributed under the GNU General Public License, available at https://sourceforge.net/projects/qure/.

Contact:  ahnven@yahoo.it; ahnven@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
NoRSE: noise reduction and state evaluator for high-frequency single event traces
Authors: Reuel Nigel F. , Bojo Peter , Zhang Jingqing , Boghossian Ardemis A. , Ahn Jin-Ho , Kim Jong−Ho , Strano Michael S.
Published: November 2011

Summary: NoRSE was developed to analyze high-frequency datasets collected from multistate, dynamic experiments, such as molecular adsorption and desorption onto carbon nanotubes. As technology improves sampling frequency, these stochastic datasets become increasingly large with faster dynamic events. More efficient algorithms are needed to accurately locate the unique states in each time trace. NoRSE adapts and optimizes a previously published noise reduction algorithm and uses a custom peak flagging routine to rapidly identify unique event states. The algorithm is explained using experimental data from our lab and its fitting accuracy and efficiency are then shown with a generalized model of stochastic datasets. The algorithm is compared to another recently published state finding algorithm and is found to be 27 times faster and more accurate over 55% of the generalized experimental space. NoRSE is written as an M-file for Matlab.

Availability:  http://web.mit.edu/stranogroup/NoRSE.txt

Contact:  strano@mit.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Rapid and Specific Detection of Burkholderia glumae in Rice Seed by Real-Time Bio-PCR Using Species-Specific Primers Based on an rhs Family Gene
Authors: Kim Byoung Kyu , Cho Min Seok , Kim Myeong Ho , Choi Hyeon Jin , Kang Man Jung , Shim Hong Sik , Ahn Tae-Young , Kim Jaisoo , Park Dong Suk
Published: November 2011

In this study, we developed a reliable, quick, and accurate quantitative polymerase chain reaction (qPCR) assay to detect grain rot caused by Burkholderia glumae in rice seed. The control of bacterial grain rot is difficult, and the only practical methods for disease management rely on the use of pathogen-free seed, appropriate culture practices, and resistant cultivars. Therefore, the specific detection of this pathogen in seed is essential for effective control of the disease. However, other Burkholderia spp. are also detected by currently available molecular and serological methods. In this study, we exploited the available genome sequence information in public databases to develop specific PCR primers for accurate diagnosis of B. glumae. An SYBR Green real-time PCR primer set was designed based on the rhs family gene (YD repeat protein) of B. glumae BGR1 because these genes are structurally diverse. The specificity of the primers was evaluated using purified DNA from 5 isolates of B. glumae, 6 different species of Burkholderia, and 18 other reference pathogenic bacteria. The assay was able to detect at least one genome equivalent of cloned amplified target DNA using purified DNA or 1 CFU per reaction when using calibrated cell suspension. This method is rapid and reliable and has great potential for analyzing large numbers of samples.
Silicon Reduces Black Sigatoka Development in Banana
Authors: Kablan L. , Lagauche A. , Delvaux B. , Legr`ve A.
Published: November 2011

The effect of silicon (Si) uptake on the susceptibility of Musa acuminata to Mycosphaerella fijiensis was investigated in three experiments conducted under controlled conditions. Plants were grown in the presence of Si or not, in pots adapted for a hydroponic culture system or in pots filled with compost. The banana leaves were inoculated after 4 or 6 months of plant growth by spraying conidial suspensions or by brushing mycelia fragments. The disease progress over time was assessed using quantitative and qualitative scales. At the end of each experiment, disease severity was also analyzed using the image analysis software ASSESS. The Si concentration in the leaves of plants supplied with Si reached 10 to 28 g/kg of dry matter. The first symptoms appeared 18 days after inoculation. The disease developed more rapidly and more severely on banana plants grown without Si than on plants supplied with Si. The areas under the disease progress curve (AUDPCs) calculated for plants grown with Si were significantly lower than the AUDPCs for plants not supplied with Si, regardless of inoculation method. Thus, Si supply could be a valuable tool in integrated pest management against M. fijiensis by reducing the disease pressure on banana.
First Report of Cymbidium mosaic virus and Odontoglossum ringspot virus in Orchids in Mexico
Authors: Soto-Valladares A. G. , De La Torre-Almaraz R. , Xoconostle-Cazares B. , Ruíz-Medrano R.
Published: November 2011

In 2010, a survey for viral diseases in commercial, orchid-producing greenhouses was carried out in Morelos, Mexico. Many symptomatic plants were observed. The most common leaf symptoms were yellow mottle, yellow streaks, and chlorotic and necrotic ringspots. Leaf samples were collected from eight symptomatic plants from the following genera: Encyclia, Oncidium, Shomburghia, Brassia, Guarianthe, Cattleya, Epidendrum, Vanilla, Xilobium, Laelia, and Brassocattleya. Samples were tested using double-antibody sandwich (DAS)-ELISA (Agdia, Elkhart, IN) with antiserum for Cymbidium mosaic virus (CymMV), Odontoglossum ringspot virus (ORSV), Cymbidium ringspot mosaic virus, and Tobacco mosaic virus (TMV) and a general antiserum for potyviruses. At least one plant from each genus was positive to CymMV and ORSV as individual or mixed infections. Encyclia and Laelia plants were the most frequently found with mixed infections by both viruses. All genera were negative for TMV and potyviruses. Total RNA extracts were obtained from all ELISA-positive samples by a modified silica capture protocol (2). Reverse transcription (RT)-PCR was carried out with general polymerase (RdRp) gene primers corresponding to the Potexvirus group (3) and specific primers for the coat protein gene (CP) of CymMV and ORSV (1). The PCR amplification from a positive sample of each genus was resolved in agarose gels. Amplification products of the expected size were obtained for CymMV and ORSV. Five CymMV RdRp gene clones from five different plants of Laelia (GenBank Accession Nos. HQ393958, HQ393959, HQ393960, HQ393961, and HQ393962), two CP gene clones of CP gene of CymMV from two different plants of Oncidium (GenBank Accession Nos. HQ393956 and HQ393957), and three CP clones of CP of ORSV from three different plants of Encyclia (GenBank Accession Nos. HQ393953, HQ393954, and HQ393955) were sequenced. The nucleotide sequences of the Mexican orchid CymMV isolates were 96 to 97% identical to CymMV sequences in the GenBank, while those of ORSV were 99 to 100% identical to deposited ORSV sequences. To our knowledge, this is the first report of CymMV and ORSV in orchids in Mexico, which are two of the most important quarantine virus in orchids in Mexico.

References: (1) P. Ajjikuttira et al. J. Gen. Virol. 86:1543, 2005. (2) J. R. Thompson et al. J. Virol. Methods 111:85, 2003. (3) R. A. A. van der Vlugt and M. Berendsen. Eur. J. Plant Pathol. 108:367, 2002.
Remote Sensing for Assessing Rhizoctonia Crown and Root Rot Severity in Sugar Beet
Authors: Reynolds Gregory J. , Windels Carol E. , MacRae Ian V. , Laguette Soizik
Published: November 2011

Rhizoctonia crown and root rot (RCRR), caused by Rhizoctonia solani AG-2-2, is an increasingly important disease of sugar beet in Minnesota and North Dakota. Disease ratings are based on subjective, visual estimates of root rot severity (0-to-7 scale, where 0 = healthy and 7 = 100% rotted, foliage dead). Remote sensing was evaluated as an alternative method to assess RCRR. Field plots of sugar beet were inoculated with R. solani AG 2-2 IIIB at different inoculum densities at the 10-leaf stage in 2008 and 2009. Data were collected for (i) hyperspectral reflectance from the sugar beet canopy and (ii) visual ratings of RCRR in 2008 at 2, 4, 6, and 8 weeks after inoculation (WAI) and in 2009 at 2, 3, 5, and 9 WAI. Green, red, and near-infrared reflectance and several calculated narrowband and wideband vegetation indices (VIs) were correlated with visual RCRR ratings, and all resulted in strong nonlinear regressions. Values of VIs were constant until at least 26 to 50% of the root surface was rotted (RCRR = 4, wilting of foliage starting to develop) and then decreased significantly as RCRR ratings increased and plants began dying. RCRR also was detected using airborne, color-infrared imagery at 0.25- and 1-m resolution. Remote sensing can detect RCRR but not before initial appearance of foliar symptoms.
Metapopulation models for seasonally migratory animals
Authors: Taylor Caz M. , Hall Richard J.
Published: November 2011

Metapopulation models are widely used to study species that occupy patchily distributed habitat, but are rarely applied to migratory species, because of the difficulty of identifying demographically independent subpopulations. Here, we extend metapopulation theory to describe the directed seasonal movement of migratory populations between two sets of habitat patches, breeding and non-breeding, with potentially different colonization and extinction rates between patch types. By extending the classic metapopulation model, we show that migratory metapopulations will persist if the product of the two colonization rates exceeds the product of extinction rates. Further, we develop a spatially realistic migratory metapopulation model and derive a landscape metric—the migratory metapopulation capacity—that determines persistence. This new extension to metapopulation theory introduces an important tool for the management and conservation of migratory species and may also be applicable to model the dynamics of two host–parasite systems.
Adaptive behaviour, tri-trophic food-web stability and damping of chaos
Authors: Visser André W. , Mariani Patrizio , Pigolotti Simone
Published: November 2011

We examine the effect of adaptive foraging behaviour within a tri-trophic food web with intra-guild predation. The intra-guild prey is allowed to adjust its foraging effort so as to achieve an optimal
per capita
growth rate in the face of realized feeding, predation risk and foraging cost. Adaptive fitness-seeking behaviour of the intra-guild prey has a stabilizing effect on the tri-trophic food-web dynamics provided that (i) a finite optimal foraging effort exists and (ii) the trophic transfer efficiency from resource to predator via the intra-guild prey is greater than that from the resource directly. The latter condition is a general criterion for the feasibility of intra-guild predation as a trophic mode. Under these conditions, we demonstrate rigorously that adaptive behaviour will always promote stability of community dynamics in the sense that the region of parameter space in which stability is achieved is larger than for the non-adaptive counterpart of the system.
Microbial to reef scale interactions between the reef-building coral
Montastraea annularis
and benthic algae
Authors: Barott Katie L. , Rodriguez-Mueller Beltran , Youle Merry , Marhaver Kristen L. , Vermeij Mark J. A. , Smith Jennifer E. , Rohwer Forest L.
Published: November 2011

Competition between reef-building corals and benthic algae is of key importance for reef dynamics. These interactions occur on many spatial scales, ranging from chemical to regional. Using microprobes, 16S rDNA pyrosequencing and underwater surveys, we examined the interactions between the reef-building coral
Montastraea annularis
and four types of benthic algae. The macroalgae
Dictyota bartayresiana
and
Halimeda opuntia
, as well as a mixed consortium of turf algae, caused hypoxia on the adjacent coral tissue. Turf algae were also associated with major shifts in the bacterial communities at the interaction zones, including more pathogens and virulence genes. In contrast to turf algae, interactions with crustose coralline algae (CCA) and
M. annularis
did not appear to be antagonistic at any scale. These zones were not hypoxic, the microbes were not pathogen-like and the abundance of coral–CCA interactions was positively correlated with per cent coral cover. We propose a model in which fleshy algae (i.e. some species of turf and fleshy macroalgae) alter benthic competition dynamics by stimulating bacterial respiration and promoting invasion of virulent bacteria on corals. This gives fleshy algae a competitive advantage over corals when human activities, such as overfishing and eutrophication, remove controls on algal abundance. Together, these results demonstrate the intricate connections and mechanisms that structure coral reefs.
Developmental control of gene copy number by repression of replication initiation and fork progression
Authors: Sher Noa , Bell George W. , Li Sharon , Nordman Jared , Eng Thomas , Eaton Matthew L. , MacAlpine David M. , Orr-Weaver Terry L.
Published: November 2011

Precise DNA replication is crucial for genome maintenance, yet this process has been inherently difficult to study on a genome-wide level in untransformed differentiated metazoan cells. To determine how metazoan DNA replication can be repressed, we examined regions selectively under-replicated in Drosophila polytene salivary glands, and found they are transcriptionally silent and enriched for the repressive H3K27me3 mark. In the first genome-wide analysis of binding of the origin recognition complex (ORC) in a differentiated metazoan tissue, we find that ORC binding is dramatically reduced within these large domains, suggesting reduced initiation as one mechanism leading to under-replication. Inhibition of replication fork progression by the chromatin protein SUUR is an additional repression mechanism to reduce copy number. Although repressive histone marks are removed when SUUR is mutated and copy number restored, neither transcription nor ORC binding is reinstated. Tethering of the SUUR protein to a specific site is insufficient to block replication, however. These results establish that developmental control of DNA replication, at both the initiation and elongation stages, is a mechanism to change gene copy number during differentiation.
Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells
Authors: Lee Bum-Kyu , Bhinge Akshay A. , Battenhouse Anna , McDaniell Ryan M. , Liu Zheng , Song Lingyun , Ni Yunyun , Birney Ewan , Lieb Jason D. , Furey Terrence S. , Crawford Gregory E. , Iyer Vishwanath R.
Published: November 2011

Cell-type diversity is governed in part by differential gene expression programs mediated by transcription factor (TF) binding. However, there are few systematic studies of the genomic binding of different types of TFs across a wide range of human cell types, especially in relation to gene expression. In the ENCODE Project, we have identified the genomic binding locations across 11 different human cell types of CTCF, RNA Pol II (RNAPII), and MYC, three TFs with diverse roles. Our data and analysis revealed how these factors bind in relation to genomic features and shape gene expression and cell-type specificity. CTCF bound predominantly in intergenic regions while RNAPII and MYC preferentially bound to core promoter regions. CTCF sites were relatively invariant across diverse cell types, while MYC showed the greatest cell-type specificity. MYC and RNAPII co-localized at many of their binding sites and putative target genes. Cell-type specific binding sites, in particular for MYC and RNAPII, were associated with cell-type specific functions. Patterns of binding in relation to gene features were generally conserved across different cell types. RNAPII occupancy was higher over exons than adjacent introns, likely reflecting a link between transcriptional elongation and splicing. TF binding was positively correlated with the expression levels of their putative target genes, but combinatorial binding, in particular of MYC and RNAPII, was even more strongly associated with higher gene expression. These data illuminate how combinatorial binding of transcription factors in diverse cell types is associated with gene expression and cell-type specific biology.
Interlocus gene conversion events introduce deleterious mutations into at least 1% of human genes associated with inherited disease
Authors: Casola Claudio , Zekonyte Ugne , Phillips Andrew D. , Cooper David N. , Hahn Matthew W.
Published: November 2011

Establishing the molecular basis of DNA mutations that cause inherited disease is of fundamental importance to understanding the origin, nature, and clinical sequelae of genetic disorders in humans. The majority of disease-associated mutations constitute single-base substitutions and short deletions and/or insertions resulting from DNA replication errors and the repair of damaged bases. However, pathological mutations can also be introduced by nonreciprocal recombination events between paralogous sequences, a phenomenon known as interlocus gene conversion (IGC). IGC events have thus far been linked to pathology in more than 20 human genes. However, the large number of duplicated gene sequences in the human genome implies that many more disease-associated mutations could originate via IGC. Here, we have used a genome-wide computational approach to identify disease-associated mutations derived from IGC events. Our approach revealed hundreds of known pathological mutations that could have been caused by IGC. Further, we identified several dozen high-confidence cases of inherited disease mutations resulting from IGC in ∼1% of all genes analyzed. About half of the donor sequences associated with such mutations are functional paralogous genes, suggesting that epistatic interactions or differential expression patterns will determine the impact upon fitness of specific substitutions between duplicated genes. In addition, we identified thousands of hitherto undescribed and potentially deleterious mutations that could arise via IGC. Our findings reveal the extent of the impact of interlocus gene conversion upon the spectrum of human inherited disease.
Development and assessment of the constipation‐related disability scale
Authors: Hart S. L. , Albiani J. J. , Crangle C. J. , Torbit L. A. , Varma M. G.
Published: November 2011

Aliment Pharmacol Ther 2012; 35: 183–192

Background  Chronic constipation is associated with impaired quality of life and physical discomfort. Although inability to engage in day‐to‐day activities has been significantly associated with psychological distress, limited research has examined this relationship in constipated samples.

Aim  To develop and validate the Constipation‐Related Disability Scale (CRDS), which assesses the extent of disability caused by constipation.

Methods  A total of 240 constipated participants and 103 healthy controls completed the CRDS. Reliability was measured with Cronbach’s coefficient alpha and test–retest reliability was assessed with intraclass correlation coefficients. Convergent, divergent and predictive validity were assessed.

Results  Component and factor analyses were used to derive two factors: Work/Leisure Activities and Activities of Daily Living, as well as a total CRDS score. Good reliability was found, with alphas ≥0.87 and intraclass correlation coefficients ≥0.85. All scales were negatively correlated with the physical health subscales of the SF‐36 (P < 0.001) and were not significantly correlated with the Epworth Sleepiness Scale and Social Desirability Scale, providing support for convergent and divergent validity, respectively. Evidence of predictive validity was supported by associations between the total CRDS with number of physician visits per year (P < 0.01), missed work in the last year (odds ratio [OR] = 1.11, 95% confidence interval [CI] = 1.06–1.19, P < 0.001) and ER visits in the last year (OR = 1.08, 95% CI = 1.00–1.16, P < 0.05).

Conclusions  The Constipation‐Related Disability Scale is the first instrument that assesses the impact of constipation on daily activities. There is evidence of strong reliability and validity of the instrument.
Large needle aspiration biopsy histology for preoperative selection of Hürthle cell thyroid nodules
Authors: Carpi Angelo , Rossi Giuseppe , Mechanick Jeffrey I , Nicolini Andrea , Camici Marcello , Russo Matteo A , Di Coscio Giancarlo
Published: November 2011

Carpi A, Rossi G, Mechanick J I, Nicolini A, Camici M, Russo M A & Di Coscio G  (2011) Histopathology  59, 892–896

Large needle aspiration biopsy histology for preoperative selection of Hürthle cell thyroid nodules

Aims:  To assess whether the large needle aspiration biopsy (LNAB) histological distinction between pure microfollicular nodules and mixed micro–macrofollicular nodules can assist preoperative selection of a Hürthle cell nodule (HCN) discovered by fine needle aspiration cytology (FNAC).

Methods and results:  In 24 HCN identified by preoperative FNAC, preoperative LNAB histology was compared with postoperative pathology. FNAC demonstrated seven benign HCN (negative), eight HCN with atypia (positive); seven suspected cancers with HC (positive); and two cancers with Hürthle cells (positive). LNAB showed mixed micro–macrofollicular hyperplastic features in 12 nodules (negative) and a microfollicular structure in 12 nodules (positive), two of which included findings of papillary cancer. Postoperative findings were benign (negative) in 16 patients and malignant (positive) in eight patients. The sensitivity and specificity for FNAC were 87.5% [seven of eight, 95% confidence interval (CI): 47.3–99.7%) and 37.5% (six of 16, 95% CI: 15.2–64.6%], respectively, and for LNAB were 87.5% (seven of eight, 95% CI: 47.3–99.7%) and 68.8% (11 of 16, 95% CI: 41.3–89.0%), respectively. FNAC results were significantly different from postoperative results (McNemar’s test, exact two‐sided P = 0.012), while LNAB results were not (McNemar’s test, exact two‐sided P = 0.219).

Conclusions:  These data suggest that LNAB histology is more accurate than FNAC cytology for the preoperative selection of HCN.
Improved detection of mycobacteria species in formalin‐fixed tissue sections
Authors: Pedersen John S , Clarke Iain , Mills John
Published: November 2011

Pedersen J S, Clarke I & Mills J  (2011) Histopathology 59,993–1005  Improved detection of mycobacteria species in formalin‐fixed tissue sections

Aims:  To develop an antibody broadly reactive against mycobacterial species, which will improve detection of mycobacteria in tissue sections by immunohistochemistry (IHC).

Methods:  A sheep antisera was developed by immunization with multiple mycobacteria, and was tested by IHC against a range of mycobacteria in tissues from many species, as well as negative tissue controls and other bacteria.

Results:  The sheep antiserum, MAS‐01, reacted with all 18 mycobacterial species tested, but did not react with uninfected inflammatory tissues. Although MAS‐01 cross‐reacted with two microbial genera which are related to mycobacteria (Corynebacteria and Proprionibacteria), it did not with Nocardia or Actinomyces. The antibody was more sensitive than the Ziehl–Neelsen stain for detection of tissue mycobacteria, and shortened the time required to identify these infections.

Conclusion:  The MAS‐01 antiserum will facilitate rapid identification of tissue mycobacterial infection by histopathologists.
The effect of using a relaxation tape on pulse, respiration, blood pressure and anxiety levels of surgical patients
Authors: Ko Yi‐Li , Lin Pi‐Chu
Published: November 2011

Aim.  This study aims to investigate the effect of a relaxation tape on levels of anxiety in surgical patients.

Background.  Surgery is a stressful event for patients. Because of uncertainty regarding surgery and anaesthesia, patients often experience heightened anxiety and fear.

Design.  A one‐group pretest–post‐test quasi‐experimental design.

Methods.  Samples were taken from surgical patients in a medical centre in northern Taiwan. The patients were given relaxation tapes the day before their scheduled surgery. Tests were conducted before and after patients listened to the tapes. STAI and respiration, pulse and blood pressure were used to collect data measurements on the anxiety level of these patients.

Results.  The average age of 80 patients was 43·14 (SD 17·27) years. After the patients listened to the relaxation tape, their respiration rate dropped from 18·4 (SD 6·9) –17·8 (SD 7·4), pulse rate dropped from 81·9 (SD 33·5) – (SD 33·7), systolic blood pressure decreased from 125·4 (SD 16) mmHg – 121·5 (SD 13·4) mmHg and STAI score dropped from 50·9 (SD 11·1) – 41·1 (SD 9·8). They all showed a significant level of difference (p < 0·05). A one‐time listen to the tape during the entire hospital stay was the experience of the majority (66·3%) and indicated that the STAI score can be further reduced by increasing the number of tape listening sessions (F = 14·1, p < 0·001).

Conclusion.  The results show that a relaxation tape can significantly reduce the level of anxiety and vital signs related to anxiety in surgical patients.

Relevance to clinical practice.  The results of this study can provide an empirical basis for nursing treatments. We recommend that relaxation tapes be included in standard of care to alleviate anxiety in surgical patients.
Use of the Internet as a source of health information amongst participants of antenatal classes
Authors: Lima‐Pereira Patricia , Bermúdez‐Tamayo Clara , Jasienska Grazyna
Published: November 2011

Aim.  To describe the pattern of use of the Internet as a source of health information by participants of antenatal classes.

Background.  There is a lack of information about the frequency of Internet use amongst expectant mothers and fathers who attend antenatal classes.

Design.  A cross‐sectional descriptive study.

Methods.  Women (n = 114) and men (n = 21) were recruited. Data were collected anonymously using a self‐administered questionnaire, containing questions about Internet use, the frequency of that use, sources of information about pregnancy, preference over other non‐Internet sources, positive and negative feelings generated due to the use of the Internet and willingness to receive instructions on Internet use.

Results.  The average age of participants was 31·4 (SD 6·1) and their stage of pregnancy ranged from 24–38 weeks. 83·5% were expecting their first child. 93·5% reported that they used the Internet on a regular basis and no significant difference was found between men and women. Amongst Internet users, 97·7% sought, at some point, information on pregnancy on the Internet and 26·9% had done so in the last 24 hours. The Internet was the most popular source of information on pregnancy topics (18·5% of women and 25·8% of men used it as their primary source of information) after a physician. Commercial websites were more frequently used by people looking for information on pregnancy than sites maintained by not‐for‐profit organisations or professional unions.

Conclusions.  The Internet is widely used as a source of information amongst participants of antenatal classes, both male and female. Approximately 95% have used it at some point to find information during pregnancy, but the majority (approximately 90%) had no knowledge of websites run by not‐for‐profit organisations and preferred commercial websites.

Relevance to clinical practice.  Instead of disregarding the use of the Internet as a source of information during pregnancy, midwives should keep up to date and give their patients links to high‐quality sites.
Durability of sustained response shown in paediatric patients with chronic hepatitis C who were treated with interferon alfa‐2b plus ribavirin
Authors: Kelly D. A. , Haber B. , González‐Peralta R. P. , Murray K. F. , Jonas M. M. , Molleston J. P. , Narkewicz M. R. , Sinatra F. R. , Lang T. , Lachaux A. , Wirth S. , Shelton M. , Te H. S. , Pollack H. , Deng W. , Noviello S. , Albrecht J. K.
Published: November 2011

Summary.  Long‐term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long‐term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long‐term follow‐up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa‐2b plus ribavirin (IFN/R). Ninety‐seven of 147 children with CHC, who were treated with IFN/R and completed the 6‐month follow‐up in two previous clinical trials, participated in this long‐term follow‐up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24‐week post‐treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5‐year follow‐up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow‐up with the same genotype. Kaplan–Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low‐positive HCV RNA levels (n = 4) or missing HCV RNA at the 24‐week follow‐up visit (n = 2) in the initial treatment studies had virologic response during this long‐term follow‐up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post‐treatment. Mean height percentile at the end of the 5‐year follow‐up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long‐term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long‐term follow‐up. Similar long‐term results could be expected after peginterferon alfa‐2b plus ribavirin treatment.
Loss of sensory and noradrenergic innervation in benign colorectal adenomatous polyps – a putative role of semaphorins 3F and 3A
Authors: Graf N. , McLean M. , Capellino S. , Schölmerich J. , Murray G. I. , El‐Omar E. M. , Straub R. H.
Published: November 2011

Background  Nerve fibers can exert trophic/anti‐trophic effects on epithelial cells. Substance P (SP) is a pro‐proliferative neuropeptide, whereas sympathetic noradrenaline is anti‐proliferative at high concentrations.

Methods  Density of noradrenergic and sensory nerve fibers and presence of nerve repellent factors specific for noradrenergic (semaphorin 3F) and sensory nerve fibers (semaphorin 3A) were investigated in colorectal adenomas.

Key Results  The pedunculus was innervated by noradrenergic fibers, whereas the mucosa was sparsely innervated. The control submucosa compared with control mucosa demonstrated increased density of noradrenergic fibers. Control tissue was much better innervated than the polyp. This was accompanied by strong expression of semaphorin 3F in epithelial cells. Density of sensory SP+ nerve fibers was higher in control colon mucosa compared with polyp mucosa, and SP+ cell clusters and semaphorin 3A‐positive cells appeared in the intercrypt space in polyps, but not in control tissue.

Conclusions & Inferences  This study demonstrated a marked loss of noradrenergic and sensory nerve fibers in polyp mucosa, which was associated with a strong increase of semaphorin 3F and 3A. Up‐regulation of the sympathetic repellent semaphorin 3F in the polyps possibly triggers sympathetic repulsion and polyp growth due to the loss of anti‐proliferative noradrenaline and presence of SP from local SP+ cells.
Expanding the phenotype associated with FOXG1 mutations and in vivo FoxG1 chromatin‐binding dynamics
Authors: De Filippis R , Pancrazi L , Bjørgo K , Rosseto A , Kleefstra T , Grillo E , Panighini A , Cardarelli F , Meloni I , Ariani F , Mencarelli MA , Hayek J , Renieri A , Costa M , Mari F
Published: November 2011

Mutations in the Forkhead box G1 (FOXG1) gene, a brain specific transcriptional factor, are responsible for the congenital variant of Rett syndrome. Until now FOXG1 point mutations have been reported in 12 Rett patients. Recently seven additional patients have been reported with a quite homogeneous severe phenotype designated as the FOXG1 syndrome. Here we describe two unrelated patients with a de novo FOXG1 point mutation, p.Gln46X and p.Tyr400X, respectively, having a milder phenotype and sharing a distinctive facial appearance. Although FoxG1 action depends critically on its binding to chromatin, very little is known about the dynamics of this process. Using fluorescence recovery after photobleaching, we showed that most of the GFP‐FoxG1 fusion protein associates reversibly to chromatin whereas the remaining fraction is bound irreversibly. Furthermore, we showed that the two pathologic derivatives of FoxG1 described in this paper present a dramatic alteration in chromatin affinity and irreversibly bound fraction in comparison with Ser323fsX325 mutant (associated with a severe phenotype) and wild type Foxg1 protein. Our observations suggest that alterations in the kinetics of FoxG1 binding to chromatin might contribute to the pathological effects of FOXG1 mutations.
E‐genetics: exploring the acceptability and feasibility of using technology in cancer genetics services
Authors: Hilgart J , Hayward JA , Iredale R
Published: November 2011

Hilgart J, Hayward JA, Iredale R. E‐genetics: exploring the acceptability and feasibility of using technology in cancer genetics services.

The use of information and communication technologies (ICTs) in the delivery of cancer genetics services could improve equality of access in rural areas and help meet the increasing demand for specialist genetics services. An online patient survey and focus groups with patients and staff from the Cancer Genetics Service for Wales (CGSW) were used to explore the acceptability and feasibility of utilizing ICTs within genetics services, which we have termed e‐genetics. A total of 225 patients completed the online survey. Many aspects of e‐genetics proposed in the survey were highly acceptable to patients, including an electronic version of the family history questionnaire, an email facility for cancer genetic queries, and a computerized decision‐aid. Participants in the focus groups emphasized the importance of patient choice when developing new models of service delivery. For example, the use of genetic counselling via telemedicine was not considered to be preferable to face‐to‐face clinic appointments but could benefit those unable to travel. This article highlights the fact that e‐genetics initiatives may not be appropriate for all cancer genetics service users. However, user‐friendly developments that can be easily implemented and attend to individual needs could improve efficiency and cost‐effectiveness, whilst providing high‐quality services to remote areas.