bluuebunny/crossref_metadata_2025 huggingface dataset:
Ig gene-like molecule CD31 plays a nonredundant role in the regulation of T-cell immunity and tolerance
Authors: Ma Liang , Mauro Claudio , Cornish Georgina H. , Chai Jian-Guo , Coe David , Fu Hongmei , Patton Daniel , Okkenhaug Klaus , Franzoso Guido , Dyson Julian , Nourshargh Sussan , Marelli-Berg Federica M.
Published: October 2010

CD31 is an Ig-like molecule expressed by leukocytes and endothelial cells with an established role in the regulation of leukocyte trafficking. Despite genetic deletion of CD31 being associated with exacerbation of T cell-mediated autoimmunity, the contribution of this molecule to T-cell responses is largely unknown. Here we report that tumor and allograft rejection are significantly enhanced in CD31-deficient mice, which are also resistant to tolerance induction. We propose that these effects are dependent on an as yet unrecognized role for CD31-mediated homophilic interactions between T cells and antigen-presenting cells (APCs) during priming. We show that loss of CD31 interactions leads to enhanced primary clonal expansion, increased killing capacity, and diminished regulatory functions by T cells. Immunomodulation by CD31 signals correlates with a partial inhibition of proximal T-cell receptor (TCR) signaling, specifically Zap-70 phosphorylation. However, CD31-deficient mice do not develop autoimmunity due to increased T-cell death following activation, and we show that CD31 triggering induces Erk-mediated prosurvival activity in T cells either in conjunction with TCR signaling or autonomously. We conclude that CD31 functions as a nonredundant comodulator of T-cell responses, which specializes in sizing the ensuing immune response by setting the threshold for T-cell activation and tolerance, while preventing memory T-cell death.
RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in
Drosophila
Authors: Mueller Stefanie , Gausson Valérie , Vodovar Nicolas , Deddouche Safia , Troxler Laurent , Perot Jonathan , Pfeffer Sébastien , Hoffmann Jules A. , Saleh Maria-Carla , Imler Jean-Luc
Published: October 2010

Activation of innate antiviral responses in multicellular organisms relies on the recognition of structural differences between viral and cellular RNAs. Double-stranded (ds)RNA, produced during viral replication, is a well-known activator of antiviral defenses and triggers interferon production in vertebrates and RNAi in invertebrates and plants. Previous work in mammalian cells indicates that negative-strand RNA viruses do not appear to generate dsRNA, and that activation of innate immunity is triggered by the recognition of the uncapped 5′ ends of viral RNA. This finding raises the question whether antiviral RNAi, which is triggered by the presence of dsRNA in insects, represents an effective host-defense mechanism against negative-strand RNA viruses. Here, we show that the negative-strand RNA virus vesicular stomatitis virus (VSV) does not produce easily detectable amounts of dsRNA in
Drosophila
cells. Nevertheless, RNAi represents a potent response to VSV infection, as illustrated by the high susceptibility of RNAi-defective mutant flies to this virus. VSV-derived small RNAs produced in infected cells or flies uniformly cover the viral genome, and equally map the genome and antigenome RNAs, indicating that they derive from dsRNA. Our findings reveal that RNAi is not restricted to the defense against positive-strand or dsRNA viruses but can also be highly efficient against a negative-strand RNA virus. This result is of particular interest in view of the frequent transmission of medically relevant negative-strand RNA viruses to humans by insect vectors.
Compartment-Restricted Biotinylation Reveals Novel Features of Prion Protein Metabolism in Vivo
Authors: Emerman Amy B. , Zhang Zai-Rong , Chakrabarti Oishee , Hegde Ramanujan S.
Published: October 2010

Proteins are often made in more than one form, with alternate versions sometimes residing in different cellular compartments than the primary species. The mammalian prion protein (PrP), a cell surface GPI-anchored protein, is a particularly noteworthy example for which minor cytosolic and transmembrane forms have been implicated in disease pathogenesis. To study these minor species, we used a selective labeling strategy in which spatially restricted expression of a biotinylating enzyme was combined with asymmetric engineering of the cognate acceptor sequence into PrP. Using this method, we could show that even wild-type PrP generates small amounts of the CtmPrP transmembrane form. Selective detection of CtmPrP allowed us to reveal its N-terminal processing, long half-life, residence in both intracellular and cell surface locations, and eventual degradation in the lysosome. Surprisingly, some human disease-causing mutants in PrP selectively stabilized CtmPrP, revealing a previously unanticipated mechanism of CtmPrP up-regulation that may contribute to disease. Thus, spatiotemporal tagging has uncovered novel aspects of normal and mutant PrP metabolism and should be readily applicable to the analysis of minor topologic isoforms of other proteins.
Detecting temporal trends in species assemblages with bootstrapping procedures and hierarchical models
Authors: Gotelli Nicholas J. , Dorazio Robert M. , Ellison Aaron M. , Grossman Gary D.
Published: October 2010

Quantifying patterns of temporal trends in species assemblages is an important analytical challenge in community ecology. We describe methods of analysis that can be applied to a matrix of counts of individuals that is organized by species (rows) and time-ordered sampling periods (columns). We first developed a bootstrapping procedure to test the null hypothesis of random sampling from a stationary species abundance distribution with temporally varying sampling probabilities. This procedure can be modified to account for undetected species. We next developed a hierarchical model to estimate species-specific trends in abundance while accounting for species-specific probabilities of detection. We analysed two long-term datasets on stream fishes and grassland insects to demonstrate these methods. For both assemblages, the bootstrap test indicated that temporal trends in abundance were more heterogeneous than expected under the null model. We used the hierarchical model to estimate trends in abundance and identified sets of species in each assemblage that were steadily increasing, decreasing or remaining constant in abundance over more than a decade of standardized annual surveys. Our methods of analysis are broadly applicable to other ecological datasets, and they represent an advance over most existing procedures, which do not incorporate effects of incomplete sampling and imperfect detection.
Evolutionary dynamics at high latitudes: speciation and extinction in polar marine faunas
Authors: Clarke Andrew , Crame J. Alistair
Published: October 2010

Ecologists have long been fascinated by the flora and fauna of extreme environments. Physiological studies have revealed the extent to which lifestyle is constrained by low temperature but there is as yet no consensus on why the diversity of polar assemblages is so much lower than many tropical assemblages. The evolution of marine faunas at high latitudes has been influenced strongly by oceanic cooling during the Cenozoic and the associated onset of continental glaciations. Glaciation eradicated many shallow-water habitats, especially in the Southern Hemisphere, and the cooling has led to widespread extinction in some groups. While environmental conditions at glacial maxima would have been very different from those existing today, fossil evidence indicates that some lineages extend back well into the Cenozoic. Oscillations of the ice-sheet on Milankovitch frequencies will have periodically eradicated and exposed continental shelf habitat, and a full understanding of evolutionary dynamics at high latitude requires better knowledge of the links between the faunas of the shelf, slope and deep-sea. Molecular techniques to produce phylogenies, coupled with further palaeontological work to root these phylogenies in time, will be essential to further progress.
Temporal turnover and the maintenance of diversity in ecological assemblages
Authors: Magurran Anne E. , Henderson Peter A.
Published: October 2010

Temporal variation in species abundances occurs in all ecological communities. Here, we explore the role that this temporal turnover plays in maintaining assemblage diversity. We investigate a three-decade time series of estuarine fishes and show that the abundances of the individual species fluctuate asynchronously around their mean levels. We then use a time-series modelling approach to examine the consequences of different patterns of turnover, by asking how the correlation between the abundance of a species in a given year and its abundance in the previous year influences the structure of the overall assemblage. Classical diversity measures that ignore species identities reveal that the observed assemblage structure will persist under all but the most extreme conditions. However, metrics that track species identities indicate a narrower set of turnover scenarios under which the predicted assemblage resembles the natural one. Our study suggests that species diversity metrics are insensitive to change and that measures that track species ranks may provide better early warning that an assemblage is being perturbed. It also highlights the need to incorporate temporal turnover in investigations of assemblage structure and function.
Transitional states in marine fisheries: adapting to predicted global change
Authors: MacNeil M. Aaron , Graham Nicholas A. J. , Cinner Joshua E. , Dulvy Nicholas K. , Loring Philip A. , Jennings Simon , Polunin Nicholas V. C. , Fisk Aaron T. , McClanahan Tim R.
Published: October 2010

Global climate change has the potential to substantially alter the production and community structure of marine fisheries and modify the ongoing impacts of fishing. Fish community composition is already changing in some tropical, temperate and polar ecosystems, where local combinations of warming trends and higher environmental variation anticipate the changes likely to occur more widely over coming decades. Using case studies from the Western Indian Ocean, the North Sea and the Bering Sea, we contextualize the direct and indirect effects of climate change on production and biodiversity and, in turn, on the social and economic aspects of marine fisheries. Climate warming is expected to lead to (i) yield and species losses in tropical reef fisheries, driven primarily by habitat loss; (ii) community turnover in temperate fisheries, owing to the arrival and increasing dominance of warm-water species as well as the reduced dominance and departure of cold-water species; and (iii) increased diversity and yield in Arctic fisheries, arising from invasions of southern species and increased primary production resulting from ice-free summer conditions. How societies deal with such changes will depend largely on their capacity to adapt—to plan and implement effective responses to change—a process heavily influenced by social, economic, political and cultural conditions.
Extensive recombination rate variation in the house mouse species complex inferred from genetic linkage maps
Authors: Dumont Beth L. , White Michael A. , Steffy Brian , Wiltshire Tim , Payseur Bret A.
Published: October 2010

The rate of recombination is a key genomic parameter that displays considerable variation among taxa. Species comparisons have demonstrated that the rate of evolution in recombination rate is strongly dependent on the physical scale of measurement. Individual recombination hotspots are poorly conserved among closely related taxa, whereas genomic-scale recombination rate variation bears a strong signature of phylogenetic history. In contrast, the mode and tempo of evolution in recombination rates measured on intermediate physical scales is poorly understood. Here, we conduct a detailed statistical comparison between two whole-genome F2genetic linkage maps constructed from experimental intercrosses between closely related house mouse subspecies (Mus musculus). Our two maps profile a common wild-derived inbred strain ofM. m. domesticuscrossed to distinct wild-derived inbred strains representative of two other house mouse subspecies,M. m. castaneusandM. m. musculus. We identify numerous orthologous genomic regions with significant map length differences between these two crosses. Because the genomes of these recently diverged house mice are highly collinear, observed differences in map length (centimorgans) are suggestive of variation in broadscale recombination rate (centimorgans per megabase) withinM. musculus. Collectively, these divergent intervals span 19% of the house mouse genome, disproportionately aggregating on the X chromosome. In addition, we uncover strong statistical evidence for a large effect, sex-linked, site-specific modifier of recombination rate segregating withinM. musculus. Our findings reveal considerable variation in the megabase-scale recombination landscape among recently diverged taxa and underscore the continued importance of genetic linkage maps in the post-genome era.
Localized hypermutation and associated gene losses in legume chloroplast genomes
Authors: Magee Alan M. , Aspinall Sue , Rice Danny W. , Cusack Brian P. , Sémon Marie , Perry Antoinette S. , Stefanović Saša , Milbourne Dan , Barth Susanne , Palmer Jeffrey D. , Gray John C. , Kavanagh Tony A. , Wolfe Kenneth H.
Published: October 2010

Point mutations result from errors made during DNA replication or repair, so they are usually expected to be homogeneous across all regions of a genome. However, we have found a region of chloroplast DNA in plants related to sweetpea (Lathyrus) whose local point mutation rate is at least 20 times higher than elsewhere in the same molecule. There are very few precedents for such heterogeneity in any genome, and we suspect that the hypermutable region may be subject to an unusual process such as repeated DNA breakage and repair. The region is 1.5 kb long and coincides with a gene, ycf4, whose rate of evolution has increased dramatically. The product of ycf4, a photosystem I assembly protein, is more divergent within the single genus Lathyrus than between cyanobacteria and other angiosperms. Moreover, ycf4 has been lost from the chloroplast genome in Lathyrus odoratus and separately in three other groups of legumes. Each of the four consecutive genes ycf4-psaI-accD-rps16 has been lost in at least one member of the legume “inverted repeat loss” clade, despite the rarity of chloroplast gene losses in angiosperms. We established that accD has relocated to the nucleus in Trifolium species, but were unable to find nuclear copies of ycf4 or psaI in Lathyrus. Our results suggest that, as well as accelerating sequence evolution, localized hypermutation has contributed to the phenomenon of gene loss or relocation to the nucleus.
Emotional and cognitive information processing: Relations to behavioral performance and hippocampal long-term potentiation in vivo during a spatial water maze training in rats
Authors: Schulz Kristina , Korz Volker
Published: October 2010

Emotionality as well as cognitive abilities contribute to the acquisition and retrieval of memories as well as to the consolidation of long-term potentiation (LTP), a cellular model of memory formation. However, little is known about the timescale and relative contribution of these processes. Therefore, we tested the effects of weak water maze training, containing both emotional and cognitive demands, on LTP in the hippocampal dentate gyrus. The population spike amplitude (PSA)-LTP was prolonged in all rats irrespective of whether they memorized the platform position or not, whereas the field excitatory postsynaptic potential (fEPSP)-LTP was impaired in good learners and enhanced in poor learners. We then dissociated the behavioral performance of rats during the water maze task by principal component analysis and by means of stress hormone concentrations into underlying “emotional” and “cognitive” factors. PSA-LTP was associated with “emotional” and fEPSP-LTP with “cognitive” behavior. PSA-LTP was depotentiated after the blockade of corticosterone binding mineralocorticoid receptors (MRs) in trained animals, while fEPSP-LTP was unaffected. These results suggest that synaptic processing and encoding of emotional information in the hippocampal dentate gyrus is realized fast and further information transfer is detectable by the reinforcement of PSA-LTP, whereas that of cognitive memories is long lasting.
The Cytoskeleton and the Peroxisomal-Targeted SNOWY COTYLEDON3 Protein Are Required for Chloroplast Development in Arabidopsis
Authors: Albrecht Verónica , Šimková Klára , Carrie Chris , Delannoy Etienne , Giraud Estelle , Whelan Jim , Small Ian David , Apel Klaus , Badger Murray R. , Pogson Barry James
Published: October 2010

Here, we describe the snowy cotyledon3 (sco3-1) mutation, which impairs chloroplast and etioplast development in Arabidopsis thaliana seedlings. SCO3 is a member of a largely uncharacterized protein family unique to the plant kingdom. The sco3-1 mutation alters chloroplast morphology and development, reduces chlorophyll accumulation, impairs thylakoid formation and photosynthesis in seedlings, and results in photoinhibition under extreme CO2 concentrations in mature leaves. There are no readily apparent changes to chloroplast biology, such as transcription or assembly that explain the disruption to chloroplast biogenesis. Indeed, SCO3 is actually targeted to another organelle, specifically to the periphery of peroxisomes. However, impaired chloroplast development cannot be attributed to perturbed peroxisomal metabolic processes involving germination, fatty acid β-oxidation or photorespiration, though there are so far undescribed changes in low and high CO2 sensitivity in seedlings and young true leaves. Many of the chloroplasts are bilobed, and some have persistent membranous extensions that encircle other cellular components. Significantly, there are changes to the cytoskeleton in sco3-1, and microtubule inhibitors have similar effects on chloroplast biogenesis as sco3-1 does. The localization of SCO3 to the periphery of the peroxisomes was shown to be dependent on a functional microtubule cytoskeleton. Therefore, the microtubule and peroxisome-associated SCO3 protein is required for chloroplast development, and sco3-1, along with microtubule inhibitors, demonstrates an unexpected role for the cytoskeleton and peroxisomes in chloroplast biogenesis.
‘Keeping families and children in mind’: an evaluation of a web‐based workforce resource
Authors: Reupert Andrea , Foster Kim , Maybery Darryl , Eddy Kylie , Fudge Elizabeth
Published: October 2010

This study outlines pilot evaluation data of the web‐based training resource ‘Keeping Families and Children in Mind’, designed for clinicians who work with families where a parent has a mental illness. The resource was developed from scoping existing workforce packages and in consultation with consumers, carers, researchers and mental‐health clinicians. Preliminary evaluation data were collected from an urban and a rural site in Australia via focus group interviews and pre‐ and post‐training questionnaires to ascertain the experiences of those who participated in the training. Additionally, training facilitators were invited to maintain journals in order to identify planning and implementation issues when using the resource. Post‐training, participants emphasized the need to work collaboratively with others, as well as the importance of acknowledging and working with the family members of consumers, especially children. Also, participants reported positive changes in knowledge, skill and confidence when working with families affected by parental mental illness. Facilitators highlighted technology issues and the need to work interactively with participants when using the resource. Recommendations regarding policy and future research conclude this paper.
Intraoperative evaluation of sentinel lymph nodes in breast cancer: comparison of frozen sections, imprint cytology and immunocytochemistry
Authors: Francz M. , Egervari K. , Szollosi Z.
Published: October 2010

M. Francz, K. Egervari and Z. Szollosi Intraoperative evaluation of sentinel lymph nodes in breast cancer: comparison of frozen sections, imprint cytology and immunocytochemistry

Objective:  We analysed the utility of imprint cytology with rapid immunocytochemistry and frozen section analysis for the evaluation of sentinel lymph nodes in breast cancer patients.

Methods:  The sensitivity, specificity, and positive and negative predictive values have been calculated for each method individually, each pair and all three together. We compared these results with those of routinely processed paraffin sections.

Results:  The sensitivity and specificity of each of the three methods for detection of metastatic carcinoma were as follows: 69.4% and 97.8% for touch imprint cytology; 58.3% and 100% for frozen sections; 68.5% and 98.9% for rapid immunocytochemistry. When the methods were combined, the highest accuracy was achieved by touch imprint cytology, frozen sections, touch imprint cytology plus rapid immunocytochemistry, or touch imprint cytology frozen section analysis and rapid immunocytochemistry, each of these having identical sensitivity and specificity of 72.2% and 97.8%, respectively.

Conclusions:  In our study the combined accuracy of the three methods was the same as combining touch imprint cytology and frozen sections or touch imprint cytology plus rapid immunocytochemistry. Rapid immunocytochemistry provides an additional parameter and preserves tissue for permanent sections.
Depressive symptoms in older female carers of adults with intellectual disabilities
Authors: Chou Y. C. , Pu C‐Y. , Fu L‐Y. , Kröger T.
Published: October 2010

Background  This survey study aims to examine the prevalence and factors associated with depressive symptoms among primary older female family carers of adults with intellectual disabilities (ID).

Method  In total, 350 female family carers aged 55 and older took part and completed the interview in their homes. The survey package contained standardised scales to assess carer self‐reported depressive symptoms, social support, caregiving burden and disease and health, as well as adult and carer sociodemographic information. Multiple linear regressions were used to identify the factors associated with high depressive symptoms in carers.

Results  Between 64% and 72% of these carers were classified as having high depressive symptoms. The factors associated with carer self‐reported depressive symptoms were carer physical health, social support and caregiving burden; overall, the carer self‐reported physical health was a stronger factor associated with depressive symptoms than their physical disease status. The level of the adult with ID's behavioural functioning and the carer age, marital status, employment status, education level and the family income level were not significantly associated with carer depressive symptoms.

Conclusions  The factors identified in this study as correlating with self‐reported depressive symptoms suggest that researchers and mental health professionals should collaborate to help improve the physical health and social support networks of the most vulnerable older female family carers. This should reduce depressive symptoms directly among this high‐risk group.
Visual perception and frontal lobe in intellectual disabilities: a study with evoked potentials and neuropsychology
Authors: Muñoz‐Ruata J. , Caro‐Martínez E. , Martínez Pérez L. , Borja M.
Published: October 2010

Background  Perception disorders are frequently observed in persons with intellectual disability (ID) and their influence on cognition has been discussed. The objective of this study is to clarify the mechanisms behind these alterations by analysing the visual event related potentials early component, the N1 wave, which is related to perception alterations in several pathologies. Additionally, the relationship between N1 and neuropsychological visual tests was studied with the aim to understand its functional significance in ID persons.

Method  A group of 69 subjects, with etiologically heterogeneous mild ID, performed an odd‐ball task of active discrimination of geometric figures. N1a (frontal) and N1b (post‐occipital) waves were obtained from the evoked potentials. They also performed several neuropsychological tests.

Results  Only component N1a, produced by the target stimulus, showed significant correlations with the visual integration, visual semantic association, visual analogical reasoning tests, Perceptual Reasoning Index (Wechsler Intelligence Scale for Children Fourth Edition) and intelligence quotient.

Conclusions  The systematic correlations, produced by the target stimulus in perceptual abilities tasks, with the N1a (frontal) and not with N1b (posterior), suggest that the visual perception process involves frontal participation. These correlations support the idea that the N1a and N1b are not equivalent.

The relationship between frontal functions and early stages of visual perception is revised and discussed, as well as the frontal contribution with the neuropsychological tests used. A possible relationship between the frontal activity dysfunction in ID and perceptive problems is suggested. Perceptive alteration observed in persons with ID could indeed be because of altered sensory areas, but also to a failure in the frontal participation of perceptive processes conceived as elaborations inside reverberant circuits of perception–action.
Polymorphism in 3′‐untranslated region of toll‐like receptor 4 gene is associated with protection from hepatitis B virus recurrence after liver transplantation
Authors: Zhou L. , Wei B. , Xing C. , Xie H. , Yu X. , Wu L. , Zheng S.
Published: October 2010

L. Zhou, B. Wei, C. Xing, H. Xie, X. Yu, L. Wu, S. Zheng. Polymorphism in 3′‐untranslated region of toll‐like receptor 4 gene is associated with protection from hepatitis B virus recurrence after liver transplantation Transpl Infect Dis 2011: 13: 250–258. All rights reserved

Background
Hepatitis B virus (HBV) recurrence is one of the more severe complications following liver transplantation. Toll‐like receptors (TLRs) play a key role in human immunity by recognizing various bacteria, viruses, fungi, and parasites. Single nucleotide polymorphisms (SNPs) in the TLRs are thought to have an impact on the susceptibility to some pathogens. This study focused on the association between polymorphisms in the TLRs and HBV recurrence after liver transplantation in Han Chinese patients.

Methods. A total of 41 tag SNPs in TLRs were detected by the snapshot technique in 125 patients with primary HBV‐related diseases receiving liver transplantation in our center from 2004 to 2008.

Results. By comparing the genetic variations and clinical data between the HBV recurrence patients and nonrecurrence patients, we found that the variant genotype of rs11536889 (TLR4) was significantly associated with HBV recurrence after liver transplantation (P=0.040, odds ratio was 0.390, 95% confidence interval 0.159–0.957).

Conclusion. Our findings indicate that polymorphism in 3′‐untranslated regions of the TLR4 gene may be related to protection from HBV recurrence after liver transplantation in Han Chinese patients.
Conception Rates in Ewes after AI with Ram Semen Preserved in Milk–Egg Yolk Extenders Supplemented with Glycerol
Authors: Olivera‐Muzante J , Fierro S , Gil J
Published: October 2010

Contents

This study aimed at comparing the effect of ram semen preserved at 5°C on two milk‐based extenders (UHT skim milk or INRA‐96®, 5% egg yolk) supplemented with 2% glycerol, and the preservation time (24 and 48 h) on conception rates after cervical AI of ewes. In two field trials, 1198 Merino ewes were cervical AI in spontaneous oestrus. In Experiment 1, pooled semen (6 rams) was extended in UHT‐base (fresh, control) or chilled for 24 h in UHT5Y (UHT‐base 5% egg yolk), INRA5Y (INRA‐96® 5% egg yolk), UHT5Y2G (UHT5Y 2% glycerol) or INRA5Y2G (INRA5Y 2% glycerol). In Experiment 2, AI was performed with pooled semen (7 rams) used fresh (extended in UHT‐base or UHT5Y2G, control groups) or chilled (extended in UHT5Y2G) for 24 or 48 h. Conception rate was determined by ultrasound 40 days after AI. INRA‐96®– had similar conception as UHT‐preserved semen (56.7 vs 55.4%, p > 0.05). Addition of 2% glycerol did not modify the results (56.8 vs 55.2%, p > 0.05). Fresh semen extended in UHT‐base, and UHT5Y2G yielded similar conception rates (60 vs 64%, p > 0.05). Preservation for 24 or 48 h in UHT5Y2G gave similar results (49 vs 47%; p > 0.05). In conclusion, ram semen chilled for 24 h in UHT‐ or INRA‐96®‐based extenders yielded similar results, and glycerol addition did not have a detrimental effect. UHT5Y2G might be used to extend ram semen for fresh AI, or to preserve it for 24 or 48 h with acceptable results.
Emotion Socialization by Mothers and Fathers: Coherence among Behaviors and Associations with Parent Attitudes and Children's Social Competence
Authors: Baker Jason K. , Fenning Rachel M. , Crnic Keith A.
Published: October 2010

This study examined inter‐relations among different types of parental emotion socialization behaviors in 88 mothers and 76 fathers (co‐residing with participating mothers) of eight‐year‐old children. Parents completed questionnaires assessing emotion socialization behaviors, emotion‐related attitudes, and their children's social functioning. An observed parent–child emotion discourse task and a child social problem‐solving interview were also performed. Parent gender differences and concordance within couples in emotion socialization behaviors were identified for some but not all behaviors. Fathers' reactions to child emotion, family expressiveness, and fathers' emotion coaching during discussion cohered, and a model was supported in which the commonality among these behaviors was predicted by fathers' emotion‐coaching attitudes, and was associated with children's social competence. A cohesive structure for the emotion socialization construct was less clear for mothers, although attitudes predicted all three types of emotion socialization behavior (reactions, expressiveness, and coaching). Implications for developmental theory and for parent‐focused interventions are discussed.
Iodine status in pregnancy and household salt iodine content in rural Bangladesh
Authors: Shamim Abu Ahmed , Christian Parul , Schulze Kerry J. , Ali Hasmot , Kabir Alamgir , Rashid Mahbubur , Labrique Alain , Salamatullah Qauzi , West Jr Keith P.
Published: October 2010

Adequate maternal iodine intake is essential during pregnancy for the development of the foetus. To assess the extent of iodine insufficiency and its association with household iodized salt in rural Bangladesh, we measured urinary iodine and household salt iodine content among pregnant women in early (≤16 weeks, n = 1376) and late (≥32 weeks, n = 1114) pregnancy. Salt (∼20 g) and a spot urine sample (∼10 mL) were collected from women participating in a randomized, placebo‐controlled trial of vitamin A or beta‐carotene supplementation in rural northwestern Bangladesh during home visits in early and late pregnancy. Salt iodine was analyzed by iodometric titration, and urinary iodine by the Ohashi method. Almost all salt samples had some detectable iodine, but over 75% contained <15 ppm. Median (interquartile range) urinary iodine concentrations were 66 (34–133) and 55 (28–110) µg L−1 in early and late pregnancy, respectively; urinary iodine <150 µg L−1 was found in ∼80% of women at both times in pregnancy. Although the risk of iodine insufficiency declined with increasing iodine content of household salt (P for trend <0.05), median urinary iodine did not reach 150 µg L−1 until iodine in household salt was at least 32 ppm and 51 ppm during early and late pregnancy, respectively. Despite a national policy on universal salt iodization, salt iodine content remains insufficient to maintain adequate maternal iodine status throughout pregnancy in rural northern Bangladesh. Alternative measures like direct iodine supplementation during pregnancy could be considered to assure adequate iodine status during this high‐risk period of life.
Report of the 18th follow‐up survey of primary liver cancer in Japan
Authors: Ikai Iwao , Kudo Masatoshi , Arii Shigeki , Omata Masao , Kojiro Masamichi , Sakamoto Michiie , Takayasu Kenichi , Hayashi Norio , Makuuchi Masatoshi , Matsuyama Yutaka , Monden Morito
Published: October 2010

In the 18th Nationwide Follow‐Up Survey of Primary Liver Cancer in Japan, 20 753 people were newly registered as patients with primary liver cancer at 544 medical institutions over a period of 2 years (from 1 January 2004 to 31 December 2005). Of these patients, 94.0% had hepatocellular carcinoma (HCC) and 4.4% had intrahepatic cholangiocarcinoma (ICC). In addition, 30 677 follow‐up patients were registered in the survey. Epidemiological and clinicopathological factors, diagnosis and treatment were investigated in the newly registered patients. Compared with the 17th follow‐up survey, this follow‐up survey in HCC indicated an increase in elder patients and women, a decrease in patients positive for hepatitis B surface antigen and hepatitis C virus antibody, and a decrease in tumor size at the clinical diagnosis. In the local ablation therapy, ratio of radio frequency ablation therapy was increasing. The cumulative survival rates of newly‐registered patients between 1994 and 2005 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified by background factors and treatment. The cumulative survival rates of newly‐registered patients between 1978 and 2005 divided into three groups (1978–1985, 1986–1995 and 1996–2005) were also calculated. The data obtained in this follow‐up survey should contribute to future research and medical practice for primary liver cancer.
Blanking characteristics of a miniature electron beam column
Authors: Silver C. S. , Spallas J. P. , Muray L. P.
Published: October 2010

A commercial field emission scanning electron microscopy (SEM) based around a miniature electron beam column includes an integrated electrostatic blanker, making the system well-suited for lithography. A previous version of the miniature column design demonstrated direct-write lithography with 70 nm lines and spaces written into resist. That column also demonstrated an 85 MHz blanking speed and a 6 nA beam current using a condenser lens. This article presents a study of the field emission SEM’s integrated blanking system, including measurements and simulations of the electron beam optics. Rise and settle times are discussed, as well as beam extinction ratios under various operating conditions. The column’s conjugate blanking optics are described, and measurements are presented, which suggest that the column may be used in a conjugate blanking mode for lithography. Finally, this article discusses how these results will feedback into the system design in order to improve the SEM’s existing lithography capabilities.
Why Do You Like Fat and Sugar? Ask Your Mom!
Authors: Bentley-Lewis Rhonda
Published: October 2010

A high-fat, high-sugar diet in female mice promotes a preference for a similar diet and epigenetic changes in her offspring.
Tumor Necrosis Factor Alpha Exerts Powerful Anti-Influenza Virus Effects in Lung Epithelial Cells
Authors: Seo Sang Heui , Webster Robert G.
Published: October 2010

Previous studies have associated influenza virus-induced expression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), with influenza pathogenesis in the human respiratory tract and have suggested that alpha and beta interferons are the first cytokines recruited to counteract such infection. However, we report here that TNF-α has powerful anti-influenza virus activity. When infected with influenza virus, cultured porcine lung epithelial cells expressed TNF-α in a dose-dependent manner. Expression of TNF-α was induced only by replicating virus. TNF-α showed strong antiviral activity against avian, swine, and human influenza viruses, and the antiviral effect of TNF-α was greater than that of gamma or alpha interferon. These findings suggest that TNF-α serves as the first line of defense against influenza virus infection in the natural host.
The Cyclin-Dependent Kinase Inhibitor Roscovitine Inhibits the Transactivating Activity and Alters the Posttranslational Modification of Herpes Simplex Virus Type 1 ICP0
Authors: Davido David J. , Leib David A. , Schaffer Priscilla A.
Published: October 2010

The cyclin-dependent kinase (cdk) inhibitor Roscovitine (Rosco) reduces transcription of herpes simplex virus early genes significantly, even in the presence of wild-type levels of immediate-early (IE) viral proteins, suggesting that the transactivating functions of IE proteins may require the activities of one or more Rosco-sensitive cdk (L. M. Schang, A. Rosenberg, and P. A. Schaffer, J. Virol. 73:2161–2172, 1999). Based on this observation, we sought to determine whether Rosco alters the transactivating activity and posttranslational modification state of the IE protein, infected cell protein 0 (ICP0), in KOS6β-infected Vero cells. KOS6β is a KOS-derived recombinant virus containing an ICP0-inducible ICP6 promoter::
lacZ
cassette. To monitor ICP0’s transactivating activity, KOS6β-infected cells were released from a cycloheximide (CHX)-mediated protein synthesis block into medium with or without Rosco, and β-galactosidase activity was measured. Rosco inhibited the ability of ICP0 to transactivate the ICP6 promoter by 50-fold. This inhibition was shown not to be a consequence of inhibition of ICP6 basal promoter activity or aberrant nuclear localization of ICP0. Rosco also altered the electrophoretic mobility of a portion of ICP0 molecules derived from KOS-infected cells following reversal of a CHX block. Notably, however, Rosco had only a minimal effect on the phosphorylation state of ICP0. We conclude that ICP0’s transactivating activity requires Rosco-sensitive cdks and hypothesize that these cdks regulate the functions of cellular enzymes which modify ICP0, and are, consequently, required for its transactivating activity. Thus, we propose that Rosco regulates ICP0’s posttranslational state by mechanisms other than, or in addition to, phosphorylation.
VLA-2 (α2β1) Integrin Promotes Rotavirus Entry into Cells but Is Not Necessary for Rotavirus Attachment
Authors: Ciarlet Max , Crawford Sue E. , Cheng Elly , Blutt Sarah E. , Rice Daren A. , Bergelson Jeffrey M. , Estes Mary K.
Published: October 2010

In an attempt to identify the rotavirus receptor, we tested 46 cell lines of different species and tissue origins for susceptibility to infection by threeN-acetyl-neuraminic (sialic) acid (SA)-dependent and five SA-independent rotavirus strains. Susceptibility to SA-dependent or SA-independent rotavirus infection varied depending on the cell line tested and the multiplicity of infection (MOI) used. Cells of renal or intestinal origin and transformed cell lines derived from breast, stomach, bone, or lung were all susceptible to rotavirus infection, indicating a wider host tissue range than previously appreciated. Chinese hamster ovary (CHO), baby hamster kidney (BHK-21), guinea pig colon (GPC-16), rat small intestine (Rie1), and mouse duodenum (MODE-K) cells were found to support only limited rotavirus replication even at MOIs of 100 or 500, but delivery of rotavirus particles into the cytoplasm by lipofection resulted in efficient rotavirus replication. The rotavirus cell attachment protein, the outer capsid spike protein VP4, contains the sequence GDE(A) recognized by the VLA-2 (α2β1) integrin, and to test if VLA-2 is involved in rotavirus attachment and entry, we measured infection in CHO cells that lack VLA-2 and CHO cells transfected with the human α2 subunit (CHOα2) or with both the human α2 and β1 subunits (CHOα2β1) of VLA-2. Infection by SA-dependent or SA-independent rotavirus strains was 2- to 10-fold more productive in VLA-2-expressing CHO cells than in parental CHO cells, and the increased susceptibility to infection was blocked with anti-VLA-2 antibody. However, the levels of binding of rotavirus to CHO, CHOα2, and CHOα2β1 cells were equivalent and were not increased over binding to susceptible monkey kidney (MA104) cells or human colonic adenocarcinoma (Caco-2, HT-29, and T-84) cells, and binding was not blocked by antibody to the human α2 subunit. Although the VLA-2 integrin promotes rotavirus infection in CHO cells, it is clear that the VLA-2 integrin alone is not responsible for rotavirus cell attachment and entry. Therefore, VLA-2 is not involved in the initial attachment of rotavirus to cells but may play a role at a postattachment level.
A High-Capacity, Capsid-Modified Hybrid Adenovirus/Adeno-Associated Virus Vector for Stable Transduction of Human Hematopoietic Cells
Authors: Shayakhmetov Dmitry M. , Carlson Cheryl A. , Stecher Hartmut , Li Qiliang , Stamatoyannopoulos George , Lieber André
Published: October 2010

To achieve stable gene transfer into human hematopoietic cells, we constructed a new vector, ΔAd5/35.AAV. This vector has a chimeric capsid containing adenovirus type 35 fibers, which conferred efficient infection of human hematopoietic cells. The ΔAd5/35.AAV vector genome is deleted for all viral genes, allowing for infection without virus-associated toxicity. To generate high-capacity ΔAd5/35.AAV vectors, we employed a new technique based on recombination between two first-generation adenovirus vectors. The resultant vector genome contained an 11.6-kb expression cassette including the human γ-globin gene and the HS2 and HS3 elements of the β-globin locus control region. The expression cassette was flanked by adeno-associated virus (AAV) inverted terminal repeats (ITRs). Infection with ΔAd5/35.AAV allowed for stable transgene expression in a hematopoietic cell line after integration into the host genome through the AAV ITR(s). This new vector exhibits advantages over existing integrating vectors, including an increased insert capacity and tropism for hematopoietic cells. It has the potential for stable ex vivo transduction of hematopoietic stem cells in order to treat sickle cell disease.
Alterations in NF-κB and RBP-Jκ by Arenavirus Infection of Macrophages In Vitro and In Vivo
Authors: Fennewald S. M. , Aronson J. F. , Zhang L. , Herzog N. K.
Published: October 2010

Pichinde virus is an arenavirus that infects guinea pigs and serves as an animal model for human Lassa fever. An attenuated Pichinde virus variant (P2) and a virulent variant (P18) are being used to delineate pathogenic mechanisms that culminate in shock. In guinea pigs, the infection has been shown to begin in peritoneal macrophages following intraperitoneal inoculation and then spreads to the spleen and other reticuloendothelial organs. We show here that infection of the murine monocytic cell line P388D1 with either Pichinde virus variant resulted in the induction of inflammatory cytokines and effectors, including interleukin-6 and tumor necrosis factor alpha. Since these genes are regulated in part by the cellular transcription factors NF-κB and RBP-Jκ, we compared the activities of NF-κB and RBP-Jκ in P388D1 cells following infection with Pichinde virus. The attenuated P2 virus inhibited NF-κB activation and caused a shift in the size of the RBP-Jκ complex. The virulent P18 virus showed less inhibition of NF-κB and failed to alter the size of the RBP-Jκ complex. Peritoneal cells from P2-infected guinea pigs showed induction of NF-κB RelA/p50 heterodimer and p50/p50 homodimer and manifested an increase in the size of RBP-Jκ. By contrast, P18 induced large amounts of the NF-κB p50/p50 dimer but failed to induce RelA/p50 or to cause an increase in the RBP-Jκ size. Taken together, these changes suggest that the attenuated viral strain induces an “activation” of macrophages, while the virulent form of the virus does not.
Respiratory Syncytial Virus Fusion Protein Mediates Inhibition of Mitogen-Induced T-Cell Proliferation by Contact
Authors: Schlender Jörg , Walliser Gunther , Fricke Jens , Conzelmann Karl-Klaus
Published: October 2010

Human respiratory syncytial virus (HRSV) and bovine respiratory syncytial virus (BRSV) are major pathogens in infants and calves, respectively. Experimental BRSV infection of calves and lambs is associated with lymphopenia and a reduction in responsiveness of peripheral blood lymphocytes (PBLs) to mitogens ex vivo. In this report, we show that in vitro mitogen-induced proliferation of PBLs is inhibited after contact with RSV-infected and UV-inactivated cells or with cells expressing RSV envelope proteins on the cell surface. The protein responsible was identified as the RSV fusion protein (F), as cells infected with a recombinant RSV expressing F as the single envelope protein or cells transfected with a plasmid encoding F were able to induce this effect. Thus, direct contact with RSV F is necessary and sufficient to inhibit proliferation of PBLs. Interestingly, F derived from HRSV was more efficient in inhibiting human PBL proliferation, while F from BRSV was more efficient in inhibiting bovine PBLs. Since various T-cell activation markers were upregulated after presenter cell contact, T lymphocytes are viable and may still be activated by mitogen. However, a significant fraction of PBLs were delayed or defective in G0/G1to S-phase transit.
Retroviral Vectors Produced in the Cytoplasmic Vaccinia Virus System Transduce Intron-Containing Genes
Authors: Konetschny C. , Holzer G. W. , Falkner F. G.
Published: October 2010

Introns and polyadenylation (pA) sites are known to improve transcript stability and nuclear-cytoplasmic transport and are normally present in efficient gene expression vectors. Standard retroviral vectors, however, do not allow the inclusion of such sequence elements, as mRNA processing at internal splice and pA sites interferes with the production of functional full-length vector genomes. In this report we examined the capability of hybrid vaccinia/retroviral vectors to transduce complex gene cassettes with nuclear RNA processing signals within the retroviral genome. A retroviral vector was constructed that contains a gene of interest (the human coagulation factor IX [FIX] cDNA), including an intron and an internal pA site. The modified proviral vector genome was cloned downstream of a vaccinia virus promoter and was inserted into the vaccinia virus genome. Infection of a packaging cell line with the recombinant vaccinia virus vector resulted in secretion of retroviral particles at average titers of 10
5
CFU per ml of cell culture supernatant. Due to the cytoplasmic transcription and the nonrecognition of nuclear transcription signals in the vaccinia virus system, full-length transcripts were obtained that still contained the intron. In the retrovirally transduced cell lines the FIX transcripts were terminated at the internal pA site. The transcripts were quantitatively spliced, and FIX was secreted. Recombinant cell lines with stable single-copy inserts containing sequence elements necessary for efficient gene function could be generated. Thus, a relatively simple cytoplasmic system for the generation of complex retroviral vectors is described. Retroviral vectors transducing intron-containing gene cassettes may play a further role in gene therapy applications.