bluuebunny/crossref_metadata_2025 huggingface dataset:
The microtubule-binding protein Cep170 promotes the targeting of the kinesin-13 depolymerase Kif2b to the mitotic spindle
Authors: Welburn Julie P. I. , Cheeseman Iain M.
Published: October 2012

Microtubule dynamics are essential throughout mitosis to ensure correct chromosome segregation. Microtubule depolymerization is controlled in part by microtubule depolymerases, including the kinesin-13 family of proteins. In humans, there are three closely related kinesin-13 isoforms (Kif2a, Kif2b, and Kif2c/MCAK), which are highly conserved in their primary sequences but display distinct localization and nonoverlapping functions. Here we demonstrate that the N-terminus is a primary determinant of kinesin-13 localization. However, we also find that differences in the C-terminus alter the properties of kinesin-13, in part by facilitating unique protein–protein interactions. We identify the spindle-localized proteins Cep170 and Cep170R (KIAA0284) as specifically associating with Kif2b. Cep170 binds to microtubules in vitro and provides Kif2b with a second microtubule-binding site to target it to the spindle. Thus the intrinsic properties of kinesin-13s and extrinsic factors such as their associated proteins result in the diversity and specificity within the kinesin-13 depolymerase family.
Taxol-stabilized microtubules promote the formation of filaments from unmodified full-length Tau in vitro
Authors: Duan Aranda R. , Goodson Holly V.
Published: October 2012

Tau is a neuronal protein that stabilizes the microtubule (MT) network, but it also forms filaments associated with Alzheimer's disease. Understanding Tau–MT and Tau–Tau interactions would help to establish Tau function in health and disease. For many years, literature reports on Tau–MT binding behavior and affinity have remained surprisingly contradictory (e.g., 10-fold variation in Tau–MT affinity). Tau–Tau interactions have also been investigated, but whether MTs might affect Tau filament formation is unknown. We have addressed these issues through binding assays and microscopy. We assessed Tau–MT interactions via cosedimentation and found that the measured affinity of Tau varies greatly, depending on the experimental design and the protein concentrations used. To investigate this dependence, we used fluorescence microscopy to examine Tau–MT binding. Strikingly, we found that Taxol-stabilized MTs promote Tau filament formation without characterized Tau-filament inducers. We propose that these novel Tau filaments account for the incongruence in Tau–MT affinity measurements. Moreover, electron microscopy reveals that these filaments appear similar to the heparin-induced Alzheimer's model. These observations suggest that the MT-induced Tau filaments provide a new model for Alzheimer's studies and that MTs might play a role in the formation of Alzheimer's-associated neurofibrillary tangles.
The two human centrin homologues have similar but distinct functions atTetrahymenabasal bodies
Authors: Vonderfecht Tyson , Cookson Michael W. , Giddings Thomas H. , Clarissa Christina , Winey Mark
Published: October 2012

Centrins are a ubiquitous family of small Ca2+-binding proteins found at basal bodies that are placed into two groups based on sequence similarity to the human centrins 2 and 3. Analyses of basal body composition in different species suggest that they contain a centrin isoform from each group. We used the ciliate protist Tetrahymena thermophila to gain a better understanding of the functions of the two centrin groups and to determine their potential redundancy. We have previously shown that the Tetrahymena centrin 1 (Cen1), a human centrin 2 homologue, is required for proper basal body function. In this paper, we show that the Tetrahymena centrin 2 (Cen2), a human centrin 3 homologue, has functions similar to Cen1 in basal body orientation, maintenance, and separation. The two are, however, not redundant. A further examination of human centrin 3 homologues shows that they function in a manner distinct from human centrin 2 homologues. Our data suggest that basal bodies require a centrin from both groups in order to function correctly.
The kinesin-14 Klp2 is negatively regulated by the SIN for proper spindle elongation and telophase nuclear positioning
Authors: Mana-Capelli Sebastian , McLean Janel R. , Chen Chun-Ti , Gould Kathleen L. , McCollum Dannel
Published: October 2012

In Schizosaccharomyces pombe, a late mitotic kinase pathway called the septation initiation network (SIN) triggers cytokinesis. Here we show that the SIN is also involved in regulating anaphase spindle elongation and telophase nuclear positioning via inhibition of Klp2, a minus end–directed kinesin-14. Klp2 is known to localize to microtubules (MTs) and have roles in interphase nuclear positioning, mitotic chromosome alignment, and nuclear migration during karyogamy (nuclear fusion during mating). We observe SIN-dependent disappearance of Klp2 from MTs in anaphase, and we find that this is mediated by direct phosphorylation of Klp2 by the SIN kinase Sid2, which abrogates loading of Klp2 onto MTs by inhibiting its interaction with Mal3 (EB1 homologue). Disruption of Klp2 MT localization is required for efficient anaphase spindle elongation. Furthermore, when cytokinesis is delayed, SIN inhibition of Klp2 acts in concert with microtubules emanating from the equatorial microtubule-organizing center to position the nuclei away from the cell division site. These results reveal novel functions of the SIN in regulating the MT cytoskeleton and suggest that the SIN may have broader functions in regulating cellular organization in late mitosis than previously realized.
Sequestration of G3BP coupled with efficient translation inhibits stress granules in Semliki Forest virus infection
Authors: Panas Marc D. , Varjak Margus , Lulla Aleksei , Er Eng Kai , Merits Andres , Karlsson Hedestam Gunilla B. , McInerney Gerald M.
Published: October 2012

Dynamic, mRNA-containing stress granules (SGs) form in the cytoplasm of cells under environmental stresses, including viral infection. Many viruses appear to employ mechanisms to disrupt the formation of SGs on their mRNAs, suggesting that they represent a cellular defense against infection. Here, we report that early in Semliki Forest virus infection, the C-terminal domain of the viral nonstructural protein 3 (nsP3) forms a complex with Ras-GAP SH3-domain–binding protein (G3BP) and sequesters it into viral RNA replication complexes in a manner that inhibits the formation of SGs on viral mRNAs. A viral mutant carrying a C-terminal truncation of nsP3 induces more persistent SGs and is attenuated for propagation in cell culture. Of importance, we also show that the efficient translation of viral mRNAs containing a translation enhancer sequence also contributes to the disassembly of SGs in infected cells. Furthermore, we show that the nsP3/G3BP interaction also blocks SGs induced by other stresses than virus infection. This is one of few described viral mechanisms for SG disruption and underlines the role of SGs in antiviral defense.
Differential regulation of HMG-CoA reductase and Insig-1 by enzymes of the ubiquitin-proteasome system
Authors: Tsai Yien Che , Leichner Gil S. , Pearce Margaret M. P. , Wilson Gaye Lynn , Wojcikiewicz Richard J. H. , Roitelman Joseph , Weissman Allan M.
Published: October 2012

The endoplasmic reticulum (ER)–resident enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase catalyzes the rate-limiting step in sterol production and is the therapeutic target of statins. Understanding HMG-CoA reductase regulation has tremendous implications for atherosclerosis. HMG-CoA reductase levels are regulated in response to sterols both transcriptionally, through a complex regulatory loop involving the ER Insig proteins, and posttranslationally, by Insig-dependent protein degradation by the ubiquitin-proteasome system. The ubiquitin ligase (E3) gp78 has been implicated in the sterol-regulated degradation of HMG-CoA reductase and Insig-1 through ER-associated degradation (ERAD). More recently, a second ERAD E3, TRC8, has also been reported to play a role in the sterol-accelerated degradation of HMG-CoA reductase. We interrogated this network in gp78−/−mouse embryonic fibroblasts and also assessed two fibroblast cell lines using RNA interference. Although we consistently observe involvement of gp78 in Insig-1 degradation, we find no substantive evidence to support roles for either gp78 or TRC8 in the robust sterol-accelerated degradation of HMG-CoA reductase. We discuss factors that might lead to such discrepant findings. Our results suggest a need for additional studies before definitive mechanistic conclusions are drawn that might set the stage for development of drugs to manipulate gp78 function in metabolic disorders.
Fast protein structure alignment using Gaussian overlap scoring of backbone peptide fragment similarity
Authors: Ritchie David W. , Ghoorah Anisah W. , Mavridis Lazaros , Venkatraman Vishwesh
Published: October 2012

Motivation: Aligning and comparing protein structures is important for understanding their evolutionary and functional relationships. With the rapid growth of protein structure databases in recent years, the need to align, superpose and compare protein structures rapidly and accurately has never been greater. Many structural alignment algorithms have been described in the past 20 years. However, achieving an algorithm that is both accurate and fast remains a considerable challenge.

Results: We have developed a novel protein structure alignment algorithm called ‘Kpax’, which exploits the highly predictable covalent geometry of Cα atoms to define multiple local coordinate frames in which backbone peptide fragments may be oriented and compared using sensitive Gaussian overlap scoring functions. A global alignment and hence a structural superposition may then be found rapidly using dynamic programming with secondary structure-specific gap penalties. When superposing pairs of structures, Kpax tends to give tighter secondary structure overlays than several popular structure alignment algorithms. When searching the CATH database, Kpax is faster and more accurate than the very efficient Yakusa algorithm, and it gives almost the same high level of fold recognition as TM-Align while being more than 100 times faster.

Availability and implementation: http://kpax.loria.fr/.

Contact: Dave.Ritchie@inria.fr.

Supplementary information:  Supplementary data are available at Bioinformatics online.
A distorted wave Born approximation target strength model for Bering Sea euphausiids
Authors: Smith Joy N. , Ressler Patrick H. , Warren Joseph D.
Published: October 2012

Smith, J. N., Ressler, P. H., and Warren, J. D. 2013. A distorted wave Born approximation target strength model for Bering Sea euphausiids. – ICES Journal of Marine Science, 70:204–214. Acoustic surveys monitor euphausiid populations in the Bering Sea because of their importance as prey for walleye pollock and other organisms. Various scattering models exist to convert acoustic backscatter data to estimates of euphausiid numerical density or biomass, but a target strength (TS) model specific to Bering Sea euphausiids has not been available. This study parameterized a distorted wave Born approximation (DWBA) scattering model using physical (length and body shape) and material (density contrast, g, and sound speed contrast, h) properties measured from live euphausiids. All model parameters (length, shape, material properties, orientation) were evaluated for their effect on predicted TS. A polynomial function was used to describe animal shape and produced smaller TS estimates compared to a taper function, as is traditionally used in DWBA scattering models of euphausiids. Animal length was positively correlated with TS, but variations in other parameters (including material properties and orientation) also produced large changes in TS. Large differences in TS between estimates calculated using measured versus literature material property values caused large variations in acoustic estimates of euphausiid numerical densities (animals m−3) which emphasizes the importance of collecting site-specific g and h measurements when possible.
Fish avoidance of research vessels and the efficacy of noise-reduced vessels: a review
Authors: De Robertis Alex , Handegard Nils Olav
Published: October 2012

De Robertis, A. and Handegard, N. O. 2013. Fish avoidance of research vessels and the efficacy of noise-reduced vessels: a review. – ICES Journal of Marine Science, 70:34–45. It has long been recognized that fish can avoid approaching vessels and that these behaviours can bias fishery surveys. Underwater noise is considered the primary stimulus, and standards for research vessel noise have been established to minimize fish reactions. We review the literature on fish reactions to vessels appearing since these recommendations were made, focusing on acoustic surveys, and compare how fish react to noise-reduced and conventional vessels. Reactions to approaching vessels are variable and difficult to predict. However, the behaviour can bias acoustic abundance measurements, and should be considered when performing acoustic surveys. The few comparisons of acoustic abundance measurements from noise-reduced and conventional vessels are contradictory, but demonstrate that the sound pressure level, on which the noise-reduction criterion is based, is insufficient to explain how fish react to survey vessels. Further research is needed to identify the stimuli fish perceive from approaching vessels and the factors affecting whether fish perceiving these stimuli will react before further recommendations to reduce vessel-avoidance reactions can be made. In the interim, measurement of the biases introduced by fish avoidance reactions during surveys, and timing of surveys when fish are in a less reactive state, may reduce errors introduced by vessel avoidance.
Bone marrow-induced Mef2c deficiency delays B-cell development and alters the expression of key B-cell regulatory proteins
Authors: Debnath Irina , Roundy Kirstin M. , Pioli Peter D. , Weis Janis J. , Weis John H.
Published: October 2012

The Mef2 family transcriptional regulator Mef2c (myocyte enhancer factor 2c) is highly expressed in maturing bone marrow and peripheral mature B-cells. To evaluate the role of this transcription factor in B-cell development, we generated a B-cell-specific conditional deletion of Mef2c using the Mb-1-Cre transgene that is expressed during the early stages of immunoglobulin rearrangement. Young mice possessing this defect demonstrated a significant impairment in B-cell numbers in bone marrow and spleen. This phenotype was evident in all B-cell subsets; however, as the animals mature, the deficit in the peripheral mature B-cell compartments was overcome. The absence of Mef2c in mature B-cells led to unique CD23+ and CD23− subsets that were evident in Mef2c knockout primary samples as well as Mef2c-deficient cultured, differentiated B-cells. Genome-wide expression analysis of immature and mature B-cells lacking Mef2c indicated altered expression for a number of key regulatory proteins for B-cell function including Ciita, CD23, Cr1/Cr2 and Tnfsf4. Chromatin immunoprecipitation analysis confirmed Mef2c binding to the promoters of these genes indicating a direct link between the presence (or absence) of Mef2c and altered transcriptional control in mature B-cells.
Recognition of viruses in the cytoplasm by RLRs and other helicases—how conformational changes, mitochondrial dynamics and ubiquitination control innate immune responses
Authors: Ng Chen Seng , Kato Hiroki , Fujita Takashi
Published: October 2012

Mammalian cells possess multiple sensors for recognition of invasion by a broad range of microbes. This recognition occurs through specific molecular signatures found across various pathogens. Toll-like receptors (TLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and C-type lectin receptors (CLRs) are the major cellular pathogen-recognition receptors (PRRs) responsible for this recognition. TLRs are transmembrane sensors, whereas other PRRs mainly localize in the cytoplasm for the activation of type I interferons and pro-inflammatory cytokines. Among these PRRs, RLRs are well known for their indispensable role in sensing the invasion of RNA viruses. This review summarizes recent advances in knowledge about viral recognition by RLRs and their signalling pathways, and introduces newly emerging RNA helicases involved in innate immune responses.
The escape fraction of ionizing photons from high-redshift galaxies from data-constrained reionization models
Authors: Mitra Sourav , Ferrara Andrea , Choudhury T. Roy
Published: October 2012

The escape fraction, fesc, of ionizing photons from high-redshift galaxies is a key parameter to understand cosmic reionization and star formation history. Yet, in spite of many efforts, it remains largely uncertain. We propose a novel, semi-empirical approach based on a simultaneous match of the most recently determined luminosity functions of galaxies in the redshift range 6 ≤ z ≤ 10 with reionization models constrained by a large variety of experimental data. From this procedure, we obtain the evolution of the best-fitting values of fesc along with their 2σ limits. We find that, averaged over the galaxy population, (i) the escape fraction increases from fesc = 0.068+ 0.054− 0.047 at z = 6 to fesc = 0.179+ 0.331− 0.132 at z = 8 and (ii) at z = 10 we can only put a lower limit of fesc > 0.146. Thus, although errors are large, there is an indication of a 2.6 times increase of the average escape fraction from z = 6 to 8, which might partially release the ‘starving reionization’ problem.
Transcriptional regulation of brain gene expression in response to a territorial intrusion
Authors: Sanogo Yibayiri O. , Band Mark , Blatti Charles , Sinha Saurabh , Bell Alison M.
Published: October 2012

Aggressive behaviour associated with territorial defence is widespread and has fitness consequences. However, excess aggression can interfere with other important biological functions such as immunity and energy homeostasis. How the expression of complex behaviours such as aggression is regulated in the brain has long intrigued ethologists, but has only recently become amenable for molecular dissection in non-model organisms. We investigated the transcriptomic response to territorial intrusion in four brain regions in breeding male threespined sticklebacks using expression microarrays and quantitative polymerase chain reaction (qPCR). Each region of the brain had a distinct genomic response to a territorial challenge. We identified a set of genes that were upregulated in the diencephalon and downregulated in the cerebellum and the brain stem.Cis-regulatory network analysis suggested transcription factors that regulated or co-regulated genes that were consistently regulated in all brain regions and others that regulated gene expression in opposing directions across brain regions. Our results support the hypothesis that territorial animals respond to social challenges via transcriptional regulation of genes in different brain regions. Finally, we found a remarkably close association between gene expression and aggressive behaviour at the individual level. This study sheds light on the molecular mechanisms in the brain that underlie the response to social challenges.
Exclusive Breastfeeding and Other Foods in the First Six Months of Life: Effects on Nutritional Status and Body Composition of Brazilian Children
Authors: Magalhães Taís C. A. , Vieira Sarah A. , Priore Silvia E. , Ribeiro Andréia Q. , Lamounier Joel A. , Franceschini Sylvia C. C. , Sant'Ana Luciana F. R.
Published: October 2012

Objective. To evaluate the effect of exclusive breastfeeding and consumption of other foods in the first six months of life in the nutritional status and body composition of children.Methods. A retrospective cohort study with 185 children aged from 4 to 7 years was monitored during the first months of life in a program of support to breastfeeding. We evaluated weight, height, waist circumference, and body composition by using DEXA. The nutritional status was assessed by the BMI/age index. The parameters of adiposity were classified by using as the cutoff point, the 85th percentile of the sample itself, according to gender and age. Confounding factors considered were variables related to maternal, pregnancy, birth, sociodemographic, health, lifestyle, and diet. Bivariate and multivariate analyses were performed, the latter by means of multiple logistic regression.Results. The median exclusive breastfeeding was 3 months. Of the children, 42.7% received cow’s milk and 35.7% received infant formula. Regarding nutritional status, 21.1% of the children showed changes. The variables of infant feeding were not independently associated with nutritional status and body composition of the children and there were no differences between the groups studied.Conclusion. Breastfeeding was not a protective factor to overweight and body fat in children.
Analysis of EMG Signals in Aggressive and Normal Activities by Using Higher-Order Spectra
Authors: Sezgin Necmettin
Published: October 2012

The analysis and classification of electromyography (EMG) signals are very important in order to detect some symptoms of diseases, prosthetic arm/leg control, and so on. In this study, an EMG signal was analyzed using bispectrum, which belongs to a family of higher-order spectra. An EMG signal is the electrical potential difference of muscle cells. The EMG signals used in the present study are aggressive or normal actions. The EMG dataset was obtained from the machine learning repository. First, the aggressive and normal EMG activities were analyzed using bispectrum and the quadratic phase coupling of each EMG episode was determined. Next, the features of the analyzed EMG signals were fed into learning machines to separate the aggressive and normal actions. The best classification result was 99.75%, which is sufficient to significantly classify the aggressive and normal actions.
A Hybrid Metaheuristic DE/CS Algorithm for UCAV Three-Dimension Path Planning
Authors: Wang Gaige , Guo Lihong , Duan Hong , Wang Heqi , Liu Luo , Shao Mingzhen
Published: October 2012

Three-dimension path planning for uninhabited combat air vehicle (UCAV) is a complicated high-dimension optimization problem, which primarily centralizes on optimizing the flight route considering the different kinds of constrains under complicated battle field environments. A new hybrid metaheuristic differential evolution (DE) and cuckoo search (CS) algorithm is proposed to solve the UCAV three-dimension path planning problem. DE is applied to optimize the process of selecting cuckoos of the improved CS model during the process of cuckoo updating in nest. The cuckoos can act as an agent in searching the optimal UCAV path. And then, the UCAV can find the safe path by connecting the chosen nodes of the coordinates while avoiding the threat areas and costing minimum fuel. This new approach can accelerate the global convergence speed while preserving the strong robustness of the basic CS. The realization procedure for this hybrid metaheuristic approach DE/CS is also presented. In order to make the optimized UCAV path more feasible, the B-Spline curve is adopted for smoothing the path. To prove the performance of this proposed hybrid metaheuristic method, it is compared with basic CS algorithm. The experiment shows that the proposed approach is more effective and feasible in UCAV three-dimension path planning than the basic CS model.
The Dry Eye Disease Activity Log Study
Authors: Iyer Jayant V. , Lee Sze-Yee , Tong Louis
Published: October 2012

Prolonged visually stressful activities aggravate dry eye disease (DED). The duration spent on such activities and their relationship with DED clinical features were investigated. Patients completed an activity log as they performed their usual activities over 1 typical rest day and 1 typical work day. The log included time spent in an air-conditioned environment, windy environment, driving, watching television, computer use, reading, watching a movie in the theatre, and wearing contact lens. Average daily activity hours were calculated and correlated with clinical features of DED. Thirty-five logs were returned. Positive correlation was found between watching television and episodic blurred vision (P<0.01). Computer use was negatively correlated with episodic blur vision, burning sensation, and gritty sensation (P<0.05). Negative correlation was found between time spent in windy environments, driving, reading, and certain DED symptoms (P<0.05). Reading correlated positively with severity of corneal fluorescein staining and reduced Schirmer’s values (P<0.03). The use of air conditioning correlated negatively with episodic blur vision but positively with visual blurring that improves with lubricants (P=0.02). This study is the first to evaluate the relationship between time spent on DED-aggravating activities and DED clinical features. Negative correlations between certain activities and DED symptoms suggest an unconscious modification of lifestyle to alleviate symptoms.
Effect of Predictive Cuing on Response Inhibition in Children with Heavy Prenatal Alcohol Exposure
Authors: O'Brien Jessica W. , Norman Andria L. , Fryer Susanna L. , Tapert Susan F. , Paulus Martin P. , Jones Kenneth Lyons , Riley Edward P. , Mattson Sarah N.
Published: October 2012

Background

Heavy prenatal exposure to alcohol leads to widespread cognitive deficits, including problems with attention and response inhibition. This study examined blood oxygen level‐dependent response in children with and without histories of heavy prenatal alcohol exposure during a task of response inhibition consisting of cued and noncued trials.

Methods

Children and adolescents (ages 8 to 18 years) with (alcohol‐exposed [AE] = 20) and without (control [CON] = 15) histories of heavy prenatal exposure to alcohol underwent functional magnetic resonance imaging while performing a go/no‐go task. Unbeknownst to subjects, a predictive cue preceded the no‐go stimulus in 87% of trials.

Results

Groups were matched on demographic variables and did not differ on most measures of task performance. However, following cued stimuli, the AE group demonstrated a lower hit rate to go stimuli and more conservative response bias than the CON group. AE participants demonstrated more activation during no‐go trials (inhibition) relative to go trials in the left precuneus, cingulate gyrus, anterior cingulate, and right medial frontal gyrus. During cue‐dependent response inhibition, the AE group demonstrated less activation in the left precentral and postcentral gyrus compared to the CON group.

Conclusions

Consistent with previous studies of response inhibition, the AE group demonstrated greater frontal and parietal activation when attempting to inhibit prepotent responses than the CON group, despite similar rates of commission errors. This study further demonstrated that the AE group had impaired behavioral performance on cued trials and demonstrated less activation in precentral and postcentral gyri relative to the CON group on these trials. This investigation provides evidence of impaired behavioral and neural processing of sequential information in fetal alcohol spectrum disorders, which can help improve inhibition in typical populations.
Forests, parks, palaces, and the power of place in early medieval kingship
Authors: Rollason David
Published: October 2012

Forests, parks and palaces were closely associated, so that palaces could not only have their own parks, but often occupied liminal positions between the forest and the more intensively cultivated land, or were surrounded by the forest. The power which forests and parks gave to palaces is here analysed in terms of categories of power derived from Max Weber's work: bureaucratic, personal and ideological. The first involved the forest administration and the revenues deriving from it; the second the relationship between the king and forest communities, and the role of hunting in enhancing the king's power; and the third the ideological statements about power which parks and forests could make, whether in terms of the similarity of the palace's situation to the heavenly kingdom, the symbolic representation of the king's power over the land, or the powerful traditions, ideas and literary constructs which the landscape could embody.
Analysis of F8 mRNA in haemophilia A patients with silent mutations or presumptive splice site mutations
Authors: Zimmermann M. A. , Gehrig A. , Oldenburg J. , Müller C. R. , Rost S.
Published: October 2012

Mutation screenings in haemophilia A (HA) patients identified a great variety of mutations in the factor VIII gene (F8): intron 22 or intron 1 inversions, missense mutations, nonsense mutations, small or large deletions, insertions, duplications and splice site mutations. Mutations which do not result in amino acid substitutions (silent mutations) and intronic variants located outside the splice site consensus sequences cannot be easily classified as causative for HA. In these cases, special prediction software algorithms are applied to estimate their impact on splicing. Here, we present mRNA analysis of novel F8 mutations with possible impact on splicing in four HA patients with silent mutations and seven patients with intronic variants close to or within splice site consensus sequences. Seven of eleven mutations examined in vitro could be shown to have an effect on F8 mRNA splicing and the results were compared to in silico predictions. In addition, to validate the splice site prediction software Alamut v2.0 (Interactive Biosoftware), we compared published F8 mRNA analyses with the results of the in silico prediction. In general, the results of the splice site prediction tools of Alamut were in good accordance with the experimental F8 mRNA analyses, but a fundamental discrepancy between in silico and in vitro analyses was obtained in some cases. In conclusion, this study shows that the functional classification of potential splicing mutations should not only rely on prediction software, but be rather based on mRNA analysis experiments.
A model to test how ticks and louping ill virus can be controlled by treating red grouse with acaricide
Authors: PORTER R. , NORMAN R. A. , GILBERT L.
Published: October 2012

Ticks are the most important vectors of disease‐causing pathogens in Europe. In the U.K., Ixodes ricinus L. (Ixodida: Ixodidae) transmits louping ill virus (LIV; Flaviviridae), which kills livestock and red grouse, Lagopus lagopus scoticus Lath. (Galliformes: Phasianidae), a valuable game bird. Tick burdens on grouse have been increasing. One novel method to reduce ticks and LIV in grouse may be acaricide treatment. Here, we use a mathematical model parameterized with empirical data to investigate how the acaricide treatment of grouse might theoretically control ticks and LIV in grouse. Assuming a situation in which ticks and LIV impact on the grouse population, the model predicts that grouse density will depend on deer density because deer maintain the tick population. In low deer densities, no acaricide treatment is predicted to be necessary because abundances of grouse will be high. However, at higher deer densities, the model predicts that grouse densities will increase only if high numbers of grouse are treated, and the efficacy of acaricide is high and lasts 20 weeks. The qualitative model predictions may help to guide decisions on whether to treat grouse or cull deer depending on deer densities and how many grouse can be treated. The model is discussed in terms of practical management implications.
Hair follicle stem cells can be driven into a urothelial‐like phenotype: An experimental study
Authors: Drewa Tomasz , Joachimiak Romana , Bajek Anna , Gagat Maciej , Grzanka Alina , Bodnar Magdalena , Marszalek Andrzej , Dębski Robert , Chłosta Piotr
Published: October 2012

The aim of this study was to show that conditioned medium might induce transdifferentiation of hair follicle stem cells into urothelial‐like cells. Several conditioned media and culture conditions (skeletal muscle cell conditioned medium, smooth muscle cell conditioned medium, fibroblast conditioned medium, transforming growth factor‐conditioned medium, urothelial cell conditioned medium, and co‐culture of hair follicle stem cells and urothelial cells) were used. The hair follicle stem cells phenotype from rat whisker hair follicles was checked by using flow cytometry and immunofluorescence. Cytokeratins 7, 8, 15 and 18 were used as markers. Urothelial cell conditioned medium increased the expression of urothelial markers (cytokeratin 7, cytokeratin 8, cytokeratin 18), whereas it decreased a hair follicle stem cells marker (cytokeratin 15) after 2 weeks of culture. This process depended on the time of cultivation. This medium was able to sustain the epithelial phenotype of the culture. Other media including a co‐culture system failed to induce similar changes. Smooth muscle conditioned medium resulted in a loss of cells in culture. Hair follicle stem cells are capable of differentiating into urothelial‐like cells in vitro when exposed to a bladder‐specific microenvironment.
Effects of a comprehensive intervention program, including hot bathing, on overweight adults: A randomized controlled trial
Authors: Sakurai Ryota , Fujiwara Yoshinori , Saito Kyoko , Fukaya Taro , Kim Mi‐Ji , Yasunaga Masashi , Kim Hunkyung , Ogawa Kishiko , Tanaka Chiaki , Tsunoda Nobuyo , Muraki Etsuko , Suzuki Katsuhiko , Shinkai Shoji , Watanabe Shuichiro
Published: October 2012

Aim

The objective of this study was to evaluate the effects of a comprehensive overweight intervention program, which utilizes hot bathing, on overweight, community‐dwelling middle‐aged and older adults in a randomized controlled trial.

Methods

The program was carried out in a hot bath facility and included 66 community‐dwelling middle‐aged and older Japanese adults (mean age 61.6 years, SD 7.5, 77.3% were women). The participants were randomly assigned to an exercise, diet and hot bathing intervention group (group A), exercise and diet intervention group (group B), a hot‐bathing intervention group (group C) and a control group (group D). The participants in groups A and B participated in a comprehensive intervention program (including exercise and diet classes) twice a week for 3 months, and groups A and C had hot bathing.

Results

After 3 months, the participants in group A showed a reduction in weight, abdominal circumference, body mass index and body fat percentage compared with the other intervention groups. And the lower extremity function (i.e. walking speed) had greater improvement in the participants in groups A and B compared with groups C and D. In group C, in which only hot bathing was the intervention, there were no significant improvements in measurement items.

Conclusions

Our study provides preliminary evidence that a comprehensive intervention program, including hot bathing, is useful for community residents with a tendency toward overweight. Geriatr Gerontol Int 2013; 13: 638–645.
Chronic disease risk among adults with cerebral palsy: the role of premature sarcopoenia, obesity and sedentary behaviour
Authors: Peterson M. D. , Gordon P. M. , Hurvitz E. A.
Published: October 2012

Premature declines in function among adults with cerebral palsy (CP) are generally attributed to weakness, spasticity and orthopaedic abnormalities, as well as chronic pain and fatigue. Very little research or clinical attention has been devoted to the confluence and consequences of early muscle wasting and obesity as mediators of secondary comorbidity in this population, and perhaps more importantly, to the role of lifestyle to potentiate these outcomes. At present, there are no national surveillance programmes that monitor chronic health in adults with CP; however, mortality records have demonstrated a greater prevalence of coronary heart disease as compared with the general population. Although by definition, CP is a ‘non‐progressive’ condition, secondary factors such as habitual sedentary behaviour, obesity, and premature sarcoepenia may increase the severity of functional impairment throughout adulthood, and lead to cardiometabolic disease, fragility and/or early mortality. Herein we describe the heightened health risk represented in adults with CP, and discuss the hallmark phenotypic features that coincide with ageing, obesity and cardiometabolic disorders. Moreover, we provide discussion regarding the protective role of habitual physical activity to stimulate anti‐inflammatory pathways and to ameliorate global risk. Although physical therapeutic modalities are already widely acknowledged as a vital component to improve movement quality in CP, the purpose of this review was to present a compelling case for the value of lifelong physical activity participation for both function and cardiometabolic health preservation.
Make a lasting impression: The neural consequences of re‐encountering people who emote inappropriately
Authors: Bayliss Andrew P. , Naughtin Claire K. , Lipp Ottmar V. , Kritikos Ada , Dux Paul E.
Published: October 2012

We can learn about the affective content of the environment by observing the behavior of others; their responses to stimuli tend to be appropriate to the context. To investigate the impact of observing such appropriate, compared with inappropriate, behaviors, we developed a novel behavioral task where participants observed different faces reacting to emotional scenes. We found that affective categorization of a scene was facilitated when it was presented alongside an appropriate facial expression (Experiment 1). Further, we observed that several brain areas in the right hemisphere—the putamen, insula, orbitofrontal cortex, and dorsal anterior cingulate cortex—were more activate when viewing faces that were previously observed emoting inappropriately (Experiment 2). We contend that these areas form a network that codes for the retrieval of affective conflict information generated by observing individuals producing inappropriate emotions.
HIV hyperimmune globulin or intravenous immune globulin inhibits response to an HIV vaccine
Authors: Jelonek Marie T. , Maskrey Jennifer L. , Cummins Larry M. , Arora Yogesh , Steimer Kathelyn S. , White‐Scharf Mary , Keller Margaret A.
Published: October 2012

The murine model was developed to assess the effects of maternally transferred HIV hyperimmune globulin or human intravenous immune globulin on the immunization of the offspring at 18–21 days of age with rgp120SF2‐complete Freunds adjuvant. Either HIV hyperimmune globulin or intravenous immune globulin was administered intraperitoneally to post‐partum BALB/c mice and was transferred via milk to the offspring. Both HIV hyperimmune globulin and intravenous immune globulin inhibited the offspring anti‐rgp120SF2 IgG response to the vaccine. The HIV hyperimmune globulin inhibition persisted for 28 days after immunization while the intravenous immune globulin inhibition was still present at 63 days after immunization. In addition, the intravenous immune globulin had a more generalized immunosuppressive effect, inhibiting the IgG response to both rpg120SF2 and an additional protein antigen, hen egg‐white lysozyme. Effects of maternal or exogenously administered pre‐existing antibody, including control antibodies (intravenous immune globulin), on the newborn response to HIV and other vaccines must be carefully evaluated when vaccine studies proceed in newborns.
Public health nursing and interprofessional collaboration in Norwegian municipalities: a questionnaire study
Authors: Clancy Anne , Gressnes Thomas , Svensson Tommy
Published: October 2012

The purpose of this study was to examine collaboration relating to public health nursing in different sized Norwegian municipalities. It sought to gain insight into factors that are important for successful collaboration, frequency of meeting points for collaborating activities and missing professionals in different sized municipalities. A cross‐sectional e‐post questionnaire study was carried out on a national sample of public health nurses and their collaborators. A total of 849 public health nurses (43.64%), 113 doctors at clinics and school health services (54.8%), 519 child protection workers (16.34%) and 115 midwives (41.3%) returned the questionnaire. The data were analysed using descriptive and inferential statistics. Analysis of variance (anova), Kruskal–Wallis H and chi‐square tests were used to tests differences between groups. Trust, respect and collaborative competence were ranked highest by all the respondents and formalised structures, economy and leadership ranked least important in collaborative activity. The majority of the respondents stated that they do not have fewer meeting points compared with 5 years ago. Collaboration with mental health services was missed most by all respondents. There were associations between frequency of meeting points and statements on collaboration related to municipality size. Norway is in the throes of a major coordination reform. The fact that relational factors were deemed most important for successful collaboration is an important finding at a time when focus is on structural change. The findings indicate the need for further in depth qualitative studies on reasons for ‘missing collaborators,’ on professional cultures in different sized municipalities and on interpersonal relationships. Qualitative enquiry is necessary to gain a greater understanding of how relational concepts of respect, trust and conflict are understood by municipal public health professionals.
Optical dating of sand wedges and ice‐wedge casts fromQinghaiLake area on the northeasternQinghai‐TibetanPlateau and its palaeoenvironmental implications
Authors: Liu Xiang‐Jun , Lai Zhong‐Ping
Published: October 2012

Sand wedges and ice‐wedge casts in theQinghaiLake area on the northeasternQinghai‐TibetanPlateau (QTP) occur within alluvial gravel or river terrace deposits. In this study, we report the results of quartz Optically Stimulated Luminescence (OSL) dating of the infill of five relict sand wedges and one ice‐wedge cast. Combining our dating results with previously published luminescence ages of permafrost wedges in theQinghaiLake area, we show that sand/ice wedges formed atc. 62 ka,c.45 ka and between 30 and 15 ka, and that the mean annual air temperature (MAAT) was depressed by at least ∼3°Crelative to present during the sand/ice‐wedge formation periods. This new work is partially corroborated by post‐LGMproxy records from lakes and aeolian deposits reported from the northeasternQTP. It also significantly extends the palaeoenvironmental record in the region in the period before theLGM,when other proxy records are rare, allowing a better understanding of the palaeoenvironmental conditions on the northeasternQTP.
Treatment of Chronic Headache of Cervical Origin With Lipostructure: An Observational Study
Authors: Gaetani Paolo , Klinger Marco , Levi Daniel , Bussone Gennaro , Giannasi Silvia , Caviggioli Fabio , Marazzi Mario , Broggi Giovanni
Published: October 2012

Objective.— To test feasibility, safety, and efficacy of local transplant of stromal fraction of adipose tissue in the treatment of chronic headaches of cervical origin.

Background.— Chronic headaches of cervical origin (chronic cervicogenic headache and occipital neuralgia) are characterized by persistent pain due to the involvement of the great occipital nerve, with concurrent myofascial spasm and the consequent nerve entrapment within the trapezoid tunnel.

Methods.— Tolerability and effectiveness of treatment of chronic cervicogenic headaches refractory to conventional therapies were evaluated in 24 patients. The visual analog scale of pain and the medication use diary were used in the 3 months preceding treatment; moreover, in order to verify the quality of life, patients are required to fill before surgery the Neck Pain Disability Index, the Headache Disability Index, migraine disability assessment scale questionnaire, and the short‐form 12 standard v1 questionnaire. Follow‐up examination was performed at 3 and 6 months.

Results.— In 19 cases (79.2%), a good clinical response was recorded. At 6‐month follow‐up analysis, recurrence of occipital pain was recorded in 7 cases (29.2%); there is a significant reduction in disability and pain scores, and also a significant reduction of need for pharmacologic treatment and a fast return to previous work capacities.

Conclusions.— The key point of our therapeutic strategy might be the regenerative role of stromal fraction of adipose tissue transplanted in the area of the occipital nerve entrapment; the results of the present study are encouraging both in terms of reduction of pain scores and in terms of quality of life improvement. The technique is minimally invasive, and no complications were recorded; indeed, the procedure seems to be safe and effective, and thus, a randomized study with larger follow‐up and in a large series will be started.
Effects of cocaine and withdrawal on the mouse nucleus accumbens transcriptome
Authors: Eipper‐Mains J. E. , Kiraly D. D. , Duff M. O. , Horowitz M. J. , McManus C. J. , Eipper B. A. , Graveley B. R. , Mains R. E.
Published: October 2012

Genetic association studies, pharmacological investigations and analysis of mice‐lacking individual genes have made it clear that Cocaine administration and Withdrawal have a profound impact on multiple neurotransmitter systems. The GABAergic medium spiny neurons of the nucleus accumbens (NAc) exhibit changes in the expression of genes encoding receptors for glutamate and in the signaling pathways triggered by dopamine binding to G‐protein‐coupled dopamine receptors. Deep sequence analysis provides a sensitive, quantitative and global analysis of the effects of Cocaine on the NAc transcriptome. RNA prepared from the NAc of adult male mice receiving daily injections of Saline or Cocaine, or Cocaine followed by a period of Withdrawal, was used for high‐throughput sequence analysis. Changes were validated by quantitative polymerase chain reaction or Western blot. On the basis of pathway analysis, a preponderance of the genes affected by Cocaine and Withdrawal was involved in the cadherin, heterotrimeric G‐protein and Wnt signaling pathways. Distinct subsets of cadherins and protocadherins exhibited a sustained increase or decrease in expression. Sustained down‐regulation of several heterotrimeric G‐protein β‐ and γ‐subunits was observed. In addition to altered expression of receptors for small molecule neurotransmitters, neuropeptides and endocannabinoids, changes in the expression of plasma membrane transporters and vesicular neurotransmitter transporters were also observed. The effects of chronic Cocaine and Withdrawal on the expression of genes essential to cholinergic, glutamatergic, GABAergic, peptidergic and endocannabinoid signaling are as profound as their effects on dopaminergic transmission. Simultaneous targeting of multiple Withdrawal‐specific changes in gene expression may facilitate development of new therapeutic approaches that are better able to prevent relapse.