bluuebunny/crossref_metadata_2025 huggingface dataset:
Effekte sprachlicher Förderung sowie sozialer Aspekte auf sprachliche Lernzuwächse bei Kindern mit und ohne Migrationshintergrund im Vorschulalter
Authors: Schwab Susanne , Gasteiger-Klicpera Barbara , Patzelt Doreen , Riemenschneider Ingo C. , Knapp Werner , Kucharz Diemut
Published: January 2014

Der vorliegende Beitrag untersucht die Effekte von sozialen Aspekten, Alter, Förderung im Kindergartenalltag und spezieller Sprachförderung sowie des Ausgangsniveaus von Intelligenz und sprachlichen Fähigkeiten auf die sprachlichen Lernzuwächse von Vorschulkindern. Die Leistungsentwicklung von 1150 Kindergartenkindern wurde im Längsschnitt zu Beginn und am Ende eines Kindergartenjahres erfasst. Die sprachlichen Fähigkeiten wurden mit dem Sprachscreening für das Vorschulalter (SSV) getestet.

Bei der multiplen Regressionsanalyse zur Vorhersage der Lernzuwächse im Satzgedächtnis zeigten neben dem Alter das phonologische Arbeitsgedächtnis für Nichtwörter, häuslicher Buchbestand sowie der Migrationshintergrund signifikante Einflüsse. Für Lernzuwächse im phonologischen Arbeitsgedächtnis erwiesen sich der Migrationshintergrund sowie die Ausgangsleistung im Satzgedächtnis als signifikante Prädiktoren. Einflüsse der Sprachförderung auf die sprachliche Leistungsentwicklung konnten nur bei geringen Ausgangsleistungen und bei Kindern mit Migrationshintergrund gefunden werden.
Leucoagaricus gongylophorus uses leaf-cutting ants to vector proteolytic enzymes towards new plant substrate
Authors: Kooij Pepijn W , Rogowska-Wrzesinska Adelina , Hoffmann Daniel , Roepstorff Peter , Boomsma Jacobus J , Schiøtt Morten
Published: January 2014

The mutualism between leaf-cutting ants and their fungal symbionts revolves around processing and inoculation of fresh leaf pulp in underground fungus gardens, mediated by ant fecal fluid deposited on the newly added plant substrate. As herbivorous feeding often implies that growth is nitrogen limited, we cloned and sequenced six fungal proteases found in the fecal fluid of the leaf-cutting ant Acromyrmex echinatior and identified them as two metalloendoproteases, two serine proteases and two aspartic proteases. The metalloendoproteases and serine proteases showed significant activity in fecal fluid at pH values of 5–7, but the aspartic proteases were inactive across a pH range of 3–10. Protease activity disappeared when the ants were kept on a sugar water diet without fungus. Relative to normal mycelium, both metalloendoproteases, both serine proteases and one aspartic protease were upregulated in the gongylidia, specialized hyphal tips whose only known function is to provide food to the ants. These combined results indicate that the enzymes are derived from the ingested fungal tissues. We infer that the five proteases are likely to accelerate protein extraction from plant cells in the leaf pulp that the ants add to the fungus garden, but regulatory functions such as activation of proenzymes are also possible, particularly for the aspartic proteases that were present but without showing activity. The proteases had high sequence similarities to proteolytic enzymes of phytopathogenic fungi, consistent with previous indications of convergent evolution of decomposition enzymes in attine ant fungal symbionts and phytopathogenic fungi.
Advances in the offline trace metal extraction of Mn, Co, Ni, Cu, Cd, and Pb from open ocean seawater samples with determination by sector field ICP-MS analysis
Authors: Quéroué Fabien , Townsend Ashley , van der Merwe Pier , Lannuzel Delphine , Sarthou Géraldine , Bucciarelli Eva , Bowie Andrew
Published: January 2014

A simplified, automated, low cost, portable, off-line extraction method with high throughput for trace metal analysis in seawater by SF-ICP-MS.
Microfluidic chip electrophoresis investigation of major milk proteins: study of buffer effects and quantitative approaching
Authors: Costa Fabiano Freire , Vasconcelos Paiva Brito Maria Aparecida , Moreira Furtado Marco Antônio , Martins Marta Fonseca , Leal de Oliveira Marcone Augusto , Mendonça de Castro Barra Patrícia , Amigo Garrido Lourdes , Siqueira de Oliveira dos Santos Alessa
Published: January 2014

Results of microfluidic chip technology using SEP buffer were comparable to those of SDS-PAGE and previously reported data.
Capillary electrophoresis of a wide range of DNA fragments in a mixed solution of hydroxyethyl cellulose
Authors: Li Zhenqing , Liu Chenchen , Yamaguchi Yoshinori , Ni Yi , You Qingxiang , Dou Xiaoming
Published: January 2014

We carried out capillary electrophoresis of 0.1–10.0 kilo base pair DNA fragments in a mixed hydroxyethyl cellulose (HEC) polymer.
Identification of an inhibitor of the ubiquitin–proteasome system that induces accumulation of polyubiquitinated proteins in the absence of blocking of proteasome function
Authors: Haglund Caroline , Mohanty Chitralekha , Fryknäs Mårten , D'Arcy Padraig , Larsson Rolf , Linder Stig , Rickardson Linda
Published: January 2014

The ubiquitin–proteasome system (UPS) represents one of the most promising therapeutic targets in oncology to emerge in recent years.
(Co)Polymerization of vinyl levulinate by cobalt-mediated radical polymerization and functionalization by ketoxime click chemistry
Authors: Allaoua Imène , Goi Beatriz Eleuterio , Obadia Mona M. , Debuigne Antoine , Detrembleur Christophe , Drockenmuller Eric
Published: January 2014

(Co)polymerization of vinyl levulinate (with vinyl acetate) by cobalt-mediated radical polymerization affords well-defined poly(vinyl ester)s. Pendant ketone functionalities are conjugated by ketoxime click chemistry.
Numerical approach to unbiased and driven generalized elastic model
Authors: Nezhadhaghighi M. Ghasemi , Chechkin A. , Metzler R.
Published: January 2014

From scaling arguments and numerical simulations, we investigate the properties of the generalized elastic model (GEM) that is used to describe various physical systems such as polymers, membranes, single-file systems, or rough interfaces. We compare analytical and numerical results for the subdiffusion exponent β characterizing the growth of the mean squared displacement ⟨(δh)2⟩ of the field h described by the GEM dynamic equation. We study the scaling properties of the qth order moments ⟨|δh|q⟩ with time, finding that the interface fluctuations show no intermittent behavior. We also investigate the ergodic properties of the process h in terms of the ergodicity breaking parameter and the distribution of the time averaged mean squared displacement. Finally, we study numerically the driven GEM with a constant, localized perturbation and extract the characteristics of the average drift for a tagged probe.
Allerdictor: fast allergen prediction using text classification techniques
Authors: Dang Ha X. , Lawrence Christopher B.
Published: January 2014

Motivation: Accurately identifying and eliminating allergens from biotechnology-derived products are important for human health. From a biomedical research perspective, it is also important to identify allergens in sequenced genomes. Many allergen prediction tools have been developed during the past years. Although these tools have achieved certain levels of specificity, when applied to large-scale allergen discovery (e.g. at a whole-genome scale), they still yield many false positives and thus low precision (even at low recall) due to the extreme skewness of the data (allergens are rare). Moreover, the most accurate tools are relatively slow because they use protein sequence alignment to build feature vectors for allergen classifiers. Additionally, only web server implementations of the current allergen prediction tools are publicly available and are without the capability of large batch submission. These weaknesses make large-scale allergen discovery ineffective and inefficient in the public domain.

Results: We developed Allerdictor, a fast and accurate sequence-based allergen prediction tool that models protein sequences as text documents and uses support vector machine in text classification for allergen prediction. Test results on multiple highly skewed datasets demonstrated that Allerdictor predicted allergens with high precision over high recall at fast speed. For example, Allerdictor only took ∼6 min on a single core PC to scan a whole Swiss-Prot database of ∼540 000 sequences and identified <1% of them as allergens.

Availability and implementation: Allerdictor is implemented in Python and available as standalone and web server versions at http://allerdictor.vbi.vt.edu.

Contact:  lawrence@vbi.vt.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Unveiling recurrent jets of the ULX Holmberg II X-1: evidence for a massive stellar-mass black hole?
Authors: Cseh D. , Kaaret P. , Corbel S. , Grisé F. , Lang C. , Körding E. , Falcke H. , Jonker P. G. , Miller-Jones J. C. A. , Farrell S. , Yang Y. J. , Paragi Z. , Frey S.
Published: January 2014

We report on the discovery of an apparent triple radio structure hidden inside the radio bubble of the ultraluminous X-ray source Holmberg II X-1. The morphology is consistent with a collimated jet structure, which is observed to emit optically thin synchrotron radiation. The central component has a steep radio spectrum and is brighter than the outer components indicating a renewed radio activity. We estimate a minimum time-averaged jet power of ∼2 × 1039 erg s−1 that is associated with a time-averaged isotropic X-ray luminosity of at least 4 × 1039 erg s−1. Our results suggest that Holmberg II X-1 is powered by a black hole of MBH ≥ 25 M⊙, that is inferred to be accreting at a high Eddington rate with intermittent radio activity.
Context dependency of Set1/COMPASS-mediated histone H3 Lys4 trimethylation
Authors: Thornton Janet L. , Westfield Gerwin H. , Takahashi Yoh-hei , Cook Malcolm , Gao Xin , Woodfin Ashley R. , Lee Jung-Shin , Morgan Marc A. , Jackson Jessica , Smith Edwin R. , Couture Jean-Francois , Skiniotis Georgios , Shilatifard Ali
Published: January 2014

The stimulation of trimethylation of histone H3 Lys4 (H3K4) by H2B monoubiquitination (H2Bub) has been widely studied, with multiple mechanisms having been proposed for this form of histone cross-talk. Cps35/Swd2 within COMPASS (complex of proteins associated with Set1) is considered to bridge these different processes. However, a truncated form of Set1 (762-Set1) is reported to function in H3K4 trimethylation (H3K4me3) without interacting with Cps35/Swd2, and such cross-talk is attributed to the n-SET domain of Set1 and its interaction with the Cps40/Spp1 subunit of COMPASS. Here, we used biochemical, structural, in vivo, and chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq) approaches to demonstrate that Cps40/Spp1 and the n-SET domain of Set1 are required for the stability of Set1 and not the cross-talk. Furthermore, the apparent wild-type levels of H3K4me3 in the 762-Set1 strain are due to the rogue methylase activity of this mutant, resulting in the mislocalization of H3K4me3 from the promoter-proximal regions to the gene bodies and intergenic regions. We also performed detailed screens and identified yeast strains lacking H2Bub but containing intact H2Bub enzymes that have normal levels of H3K4me3, suggesting that monoubiquitination may not directly stimulate COMPASS but rather works in the context of the PAF and Rad6/Bre1 complexes. Our study demonstrates that the monoubiquitination machinery and Cps35/Swd2 function to focus COMPASS's H3K4me3 activity at promoter-proximal regions in a context-dependent manner.
Treatment with oral beta‐blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction
Authors: Ersbøll AS , Hedegaard M , Søndergaard L , Ersbøll M , Johansen M
Published: January 2014

Objective

To investigate the effect on fetal growth of treatment with oral beta‐blockers during pregnancy in women with congenital or acquired heart disease.

Design

Historical matched cohort study.

Setting

Centre for Pregnant Women with Heart Disease, Copenhagen University Hospital, Denmark.

Population

A cohort of 175 women with heart disease, grouped according to beta‐blocker treatment, and a cohort of 627 women from the overall population matched on seven birthweight‐determining factors.

Methods

Differences between groups were tested by simple descriptive statistics and assessed using standard hypothesis tests. Associations were estimated by correlational analysis and multivariable regression.

Main outcome measure

Proportion of infants born small for gestational age (SGA).

Results

More of the infants exposed to beta‐blockers were SGA compared with non‐exposed infants (29.4 versus 15.3%; P < 0.05). After adjustment for birthweight‐determining factors, beta‐blocker treatment and maternal body mass index (BMI) were the only factors independently associated with SGA (the relative difference in expected birthweight was −8.6%; 95% CI −13.3 to −3.9%; P = 0.0004). After adjustment for BMI, beta‐blocker treatment was associated with an increased risk of SGA (OR 2.65; 95% CI 1.15–6.10; P = 0.02). In a subgroup with isolated tachyarrhythmias, SGA infants were more frequent in the beta‐blocker exposed group compared with the non‐exposed group (31 versus 10%; P < 0.005). Beta‐blocker treatment was the only independent predictor of SGA, adjusting for several factors influencing fetal growth (the relative difference in expected birthweight was −12.2%; 95% CI −19.9 to −3.9%; P = 0.001).

Conclusions

In a historical cohort of pregnancies complicated by maternal heart disease, treatment with beta‐blockers was found to be independently associated with an increased risk of delivering an SGA infant.
Homology and Molecular Dynamics Models of Toll‐Like Receptor 7 Protein and Its Dimerization
Authors: Tseng Chih‐Yuan , Gajewski Melissa , Danani Andrea , Tuszynski Jack A.
Published: January 2014

Toll‐like receptor protein 7 is a transmembrane protein playing a crucial role in the signaling pathways involved in innate immunity. Its crystal structure is not yet available, but there are several proteins possessing domains of sufficiently high homology, which enabled us to build a model of the toll‐like receptor protein 7 monomer and gain insights into dimer formation. To obtain a reliable structure prediction, we subjected this model to equilibration using molecular dynamics simulations. Furthermore, the equilibrated monomer structure was used to construct models of dimerization and to predict binding sites for small ligands. Docking studies were performed for some of the known toll‐like receptor protein 7 ligands. We determined that a new homology model generated by the LOOPP server provides a good alternative to a previously reported model. Our docking results indicate that the addition of either imiquimod or 1V209 to a toll‐like receptor protein 7 dimer changes an unfavorable interaction into a favorable one. We found that eight small molecules docked to two pockets in toll‐like receptor protein 7 bind to both pockets at pH 7 and at pH 5.5. This work provides a realistic model that could be used for drug discovery aimed at finding toll‐like receptor protein 7 dimerization activators, with potential clinical applications to a host of diseases, including cancer.
People United to Sustain Health (PUSH): A Community‐Based Participatory Research Study
Authors: Kennedy Betty M. , Katzmarzyk Peter T. , Johnson William D. , Johnson Glenda S. , McGee Bernestine B. , Champagne Catherine M. , Harsha David W. , Crawford Terri , Ryan Donna H.
Published: January 2014

The prevention of weight gain to address the obesity epidemic rather than weight loss involves promoting small changes in food choices and physical activity. People United to Sustain Health (PUSH) was designed to increase fruit and vegetable consumption, physical activity, and food security to prevent weight gain in rural adults. Forty‐nine participants were randomized into a treatment group which received access to a “Rolling Store,” nutrition education and physical activity, and a control group which received family coping classes. Forty‐one (84%) of participants completed the study. At the end of 6 months, weight for all participants was maintained from baseline to completion with no significant differences between the groups. The mean fruit consumption over 6 months for the treatment group increased and was significantly greater than change in the control group (p = 0.01). This community‐based participatory research study was considered successful because weight gain was prevented.
Cost‐effectiveness of rituximab as maintenance treatment for relapsed follicular lymphoma: results of a population‐based study
Authors: Blommestein Hedwig M. , Issa Djamila E. , Pompen Marjolein , Ten Hoor Gerhard , Hogendoorn Mels , Joosten Peter , Zweegman Sonja , Huijgens Peter C. , Uyl‐de Groot Carin A.
Published: January 2014

Objectives

On the basis of two population‐based registries, our study aims to calculate the real‐world cost‐effectiveness of rituximab maintenance compared with observation in relapsed or refractory follicular lymphoma patients who responded to second‐line chemotherapy.

Methods

Data were obtained from the EORTC20981 trial, the Netherlands Cancer Registry and two population‐based registries. A Markov model was developed to calculate cost per life year gained (LYG) and quality‐adjusted life years (QALYs) for three scenarios.

Results

Our real‐world patients were (62 years) 6 to 7 years older and had higher complete response rates to second‐line chemotherapy than the trial population. Differences between the real‐world rituximab and observation group were observed for second‐line chemotherapy and disease progression. Groups were more balanced after using propensity matching. Relying entirely on updated trial results (scenario1) in combination with local cost data resulted in ratios of €11 259 per LYG and €12 655 per QALY. For scenario2, consisting of trial efficacy and matched real‐world costs, ratios of €21 202 per LYG and €23 821 per QALY were calculated. Using real‐world matched evidence (scenario3) for both effectiveness and costs showed ratios of €10 591 per LYG and €11 245 per QALY.

Conclusion

Although differences in real‐world and trial population were found, using real‐world data as well as results from long‐term trial follow‐up showed favourable ICERs for rituximab maintenance. Nevertheless, results showed that caution is required with data synthesis, interpretation and generalisability of results. As different scenarios provide answers to different questions, we recommend healthcare decision‐makers to recognise the importance of calculating several cost‐effectiveness scenarios.
Detailed carbon chemistry in charcoals from pre‐European Māori gardens of New Zealand as a tool for understanding biochar stability in soils
Authors: Calvelo Pereira R. , Camps Arbestain M. , Kaal J. , Vazquez Sueiro M. , Sevilla M. , Hindmarsh J.
Published: January 2014

The stability of biochar, a form of charcoal intentionally made to be added to soil to sequester carbon (C) and improve its function, remains unclear. As it is not feasible to perform long‐term (decades, centuries) laboratory experiments to assess biochar evolution after soil amendment, the study of ancient archaeological charcoals can help to identify characteristics (and possibly molecular markers) associated with the decomposition and preservation dynamics of biochar in specific pedoclimatic environments. In this study, the chemical composition of the organic carbon fractions of three charcoals from pre‐European Māori gardens of New Zealand (buried > 25 cm depth) was thoroughly assessed. Complementary short‐term incubations of charcoals in sand were used to (i) evaluate the stability of C in the short‐medium term, (ii) model its mineralization processes and (iii) estimate the C turnover. Elemental analysis, thermogravimetric analysis (TG), X‐ray photoelectron spectroscopy (XPS), solid‐state 13C nuclear magnetic resonance (NMR) and pyrolysis gas chromatography/mass spectroscopy (Py‐GC‐MS) gave consistent results in describing the charring intensity and the degree of polycondensation of these charcoals. The oldest buried deposit (770 ± 50 years BP) still retained un‐charred or weakly charred lignocellulosic material, indicating that such material survived decomposition processes for several centuries. The amount of organic C mineralized in 109 days was < 0.5% of the initial charcoal‐C. No differences in MRT among samples were detected in spite of inferred differences in thermal impact. Longer‐term incubations are needed to obtain better estimates of C turnover rates in charred material.
Pre‐schoolers, parents and supermarkets: co‐shopping as a social practice
Authors: Keller Margit , Ruus Riina
Published: January 2014

The objective of this paper was to examine the co‐shopping practices of children and parents in supermarkets, i.e. the practical enactment of grocery shopping. Our special focus is on how informal consumer training occurs during parent–child interaction. We use observational data collected in spring 2008 in different Estonian supermarkets, post‐shopping interviews with parents and focus group interviews with their children. Our analysis is informed by practice theory, which helps to look in detail at how the activities in a particular situation are coordinated by understandings and procedures, and are guided by the engagement in a particular shopping trip. Co‐shopping interactions mostly revolve around particular material objects, although not exclusively. Product choice is a deeply contested area, where both parents and children face numerous pressures in this situation of two‐way socialization. There are implications for consumer education more broadly. To accomplish lasting and meaningful effects on the everyday lives of families, there has to be a wider range of actors – supermarkets, producers, governmental bodies, schools and families – who care about both formal and informal consumer education.
Molecular, genetic and stem cell‐mediated therapeutic strategies for spinal muscular atrophy (SMA)
Authors: Zanetta Chiara , Riboldi Giulietta , Nizzardo Monica , Simone Chiara , Faravelli Irene , Bresolin Nereo , Comi Giacomo P. , Corti Stefania
Published: January 2014

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease. It is the first genetic cause of infant mortality. It is caused by mutations in the survival motor neuron 1 (SMN1) gene, leading to the reduction of SMN protein. The most striking component is the loss of alpha motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment other than supportive care, although the past decade has seen a striking advancement in understanding of both SMA genetics and molecular mechanisms. A variety of disease modifying interventions are rapidly bridging the translational gap from the laboratory to clinical trials. In this review, we would like to outline the most interesting therapeutic strategies that are currently developing, which are represented by molecular, gene and stem cell‐mediated approaches for the treatment of SMA.
Sequences in the terminal protein and reverse transcriptase domains of the hepatitis B virus polymerase contribute to RNA binding and encapsidation
Authors: Cao F. , Jones S. , Li W. , Cheng X. , Hu Y. , Hu J. , Tavis J. E.
Published: January 2014

Hepatitis B virus (HBV) antiviral therapy is plagued by limited efficacy and resistance to most nucleos(t)ide analog drugs. We have proposed that the complex RNA binding mechanism of the HBV reverse transcriptase (P) may be a novel target for antivirals. We previously found that RNA binds to the duck HBV (DHBV) P through interactions with the T3 and RT1 motifs in the viral terminal protein and reverse transcriptase domains, respectively. Here, we extended these studies to HBV P. HBV T3 and RT1 synthetic peptides bound RNA in a similar manner as did analogous DHBV peptides. The HBV T3 motif could partially substitute for DHBV T3 during RNA binding and DNA priming by DHBV P, whereas replacing RT1 supported substantial RNA binding but not priming. Substituting both the HBV T3 and RT1 motifs restored near wild‐type levels of RNA binding but supported very little priming. Alanine‐scanning mutations to the HBV T3 and RT1 motifs blocked HBV ε RNA binding in vitro and pgRNA encapsidation in cells. These data indicate that both the HBV T3 and RT1 motifs contain sequences essential for HBV ε RNA binding and encapsidation of the RNA pregenome, which is similar to their functions in DHBV. Small molecules that bind to T3 and/or RT1 would therefore inhibit encapsidation of the viral RNA and block genomic replication. Such drugs would target a novel viral function and would be good candidates for use in combination with the nucleoside analogs to improve efficacy of antiviral therapy.
Intensive care units in Turkish hospitals: do they meet the minimum standards?
Authors: Türkmen Emine , Sevinç Selvet , İlhan Marziye
Published: January 2014

Background

International and national standards for ICUs have been developed to ensure patient safety and provide effective and efficient service in these units. However, global economic crises along with shortages in professional health care staff affect the ability of ICUs to meet and maintain these standards.

Aims and objectives

The aim of this study was to ascertain whether the equipment and workforce in intensive care units (ICUs) in Turkish hospitals meet current ICU standards.

Design

This is a descriptive study based on the results of a survey questionnaire.

Methods

In total, 145 ICUs in university and private hospitals in Turkey participated in this survey. Data collection was done by means of a survey questionnaire that assessed the current equipment and workforce in these ICUs.

Results

We found that 97·0% of the occupied beds in the ICUs had a cardiac monitor. Crash‐carts were present in every ICU. Transport monitors and transport ventilators were available in two of three and in one of two ICUs, respectively. In 82·8% of the ICUs, a physician (as a trainee level) was present at all times, while only a few ICUs had ICU‐care team members such as respiratory‐ and physiotherapist, clinical pharmacists and dieticians available. There was a general shortage of nursing staff in ICUs.

Conclusion

Currently, ICUs in Turkish hospitals meet the majority of standards for ICU equipment, but they fail to meet both the international and national standards for ICU workforce requirement.

Clinical relevance

Hospital and ICU managers could use our findings to compare their facilities with others or to identify areas in need of improvement.
Time Trials Predict the Competitive Performance Capacity of Junior Cross-Country Skiers
Authors: Carlsson Magnus , Carlsson Tomas , Hammarström Daniel , Malm Christer , Tonkonogi Michail
Published: January 2014

Purpose:

This study investigated whether there is a correlation between time-trial performance and competitive performance capacity of male and female junior cross-country skiers and sought to explain sex-specific competitive performance capacity through multiple-regression modeling.

Methods:

The International Ski Federation’s (FIS) junior ranking points for distance (FISdist) and sprint (FISsprint) competitions were used as performance parameters. A total of 38 elite junior (age 18.5 ± 1.0 y) cross-country skiers (24 men and 14 women) completed 3 time-trial tests: a 3-km level-running time trial (TTRun), a 2-km moderate uphill (1.2° slope) roller-skiing time trial using the double-poling technique (TTDP), and a 2-km uphill (2.8° slope) roller-skiing time trial using the diagonal-stride technique (TTDiag). The correlations were investigated using Pearson correlation analysis, and regression models were created using multiple-linear-regression analysis.

Results:

For men, FISsprint and FISdist were correlated with the times for TTRun, TTDP, and TTDiag (all P < .001). For women, FISsprint was correlated with the times for TTRun (P < .05), TTDP (P < .01), and TTDiag (P < .01), whereas FISdist was correlated only with the times for TTDP (P < .01) and TTDiag (P < .05). The models developed for FISdist and FISsprint explained 73.9–82.3% of the variance in the performance capacity of male junior cross-country skiers. No statistically valid regression model was found for the women.

Conclusions:

Running and roller-skiing time trials are useful tests for accurately predicting the performance capacity of junior cross-country skiers.
Bacterial Vesicles in Marine Ecosystems
Authors: Biller Steven J. , Schubotz Florence , Roggensack Sara E. , Thompson Anne W. , Summons Roger E. , Chisholm Sallie W.
Published: January 2014

Carbon Budding in the Ocean

Bacterial vesicles are gaining increasing attention for their roles in pathogenesis, but the abundance of these structures and their ecological roles in nonpathogenic contexts have received little notice.

Biller
et al.

(p.
183
; see the Perspective by

Scanlan

) provide evidence that membrane vesicles ∼100 nm in diameter are released by marine cyanobacteria and are a major feature of marine ecosystems. Studies of cultures of
Prochlorococcus
—the most abundant photoautotroph in the oligotrophic oceans—show that vesicles are continually released by this cyanobacterium and are abundant in the marine environment. These vesicles have properties that change the way we think about genetic and biogeochemical exchange among plankton and the dissolved organic carbon pool in marine ecosystems.
Giant Spin Oscillations in an Ultracold Fermi Sea
Authors: Krauser J. S. , Ebling U. , Fläschner N. , Heinze J. , Sengstock K. , Lewenstein M. , Eckardt A. , Becker C.
Published: January 2014

Collective Coherent Spin Dynamics

Ultracold gases have shown considerable promise for the quantum simulation of more complicated systems, such as correlated electrons in solids. Usually, researchers use two hyperfine states of the atoms to correspond to the spin up and down states of the electrons; however, these gases typically have a much richer internal state structure.

Krauser
et al.

(p.
157
) observed the coherent behavior of a gas of potassium-40 atoms that had 10 accessible internal spin states and that evolved through collisions. The spin state of the system oscillated as a whole, a surprising finding given that the atoms are fermions.
Coping with Uncertainty in Space Science Planning
Authors: Kennel Charles , Dressler Alan
Published: January 2014

Decadal surveys should propose financially responsible priorities and standing committees should facilitate their implementation.
Modular Organization of Axial Microcircuits in Zebrafish
Authors: Bagnall Martha W. , McLean David L.
Published: January 2014

Spinal Circuit Complexity in Fish

Rapid coordination of opposing muscle groups helps zebrafish zip through water.
Bagnall and McLean
(p.
197
) now describe the neuronal circuits that stabilize swimming fish in their three-dimensional environment. By studying the self-righting behavior of larval zebrafish immobilized in agar, the authors identified parallel excitatory and inhibitory circuits driving dorsal and ventral hemisegments that could be activated independently.
Biogeek Catastrophe
MaddAddam
A Novel

by Margaret Atwood

Doubleday, New York, 2013. 415 pp. $27.95. ISBN 9780385528788. McClelland and Stewart, Toronto. C$32.95. ISBN 9780771008467. Bloomsbury, London. £18.99. ISBN 9781408819708.
Authors: Goldman Michael A.
Published: January 2014

The concluding volume of Atwood's dystopian trilogy that began with
Oryx and Crake
incorporates overpopulation, climate change, genetic engineering, and a threatening new cyberreality.
U.S. Regulators Unveil New Ocean Noise Rules for Marine Mammals
Authors: Stokstad Erik
Published: January 2014

United States sets new ocean noise rules for marine mammals.
Molecular Events Accompanying Rous Sarcoma Virus Rescue from Rodent Cells and the Role of Viral Gene Complementation
Authors: Lounková Anna , Dráberová Eduarda , Šenigl Filip , Trejbalová Kateřina , Geryk Josef , Hejnar Jiří , Svoboda Jan
Published: January 2014

Transformation of rodent cells with avian Rous sarcoma virus (RSV) opened new ways to studying virus integration and expression in nonpermissive cells. We were interested in (i) the molecular changes accompanying fusion of RSV-transformed mammalian cells with avian cells leading to virus rescue and (ii) enhancement of this process by retroviral gene products. The RSV-transformed hamster RSCh cell line was characterized as producing only a marginal amount of
env
mRNA, no envelope glycoprotein, and a small amount of unprocessed Gag protein. Egress of viral unspliced genomic RNA from the nucleus was hampered, and its stability decreased. Cell fusion of the chicken DF-1 cell line with RSCh cells led to production of
env
mRNA, envelope glycoprotein, and processed Gag and virus-like particle formation. Proteosynthesis inhibition in DF-1 cells suppressed steps leading to virus rescue. Furthermore, new aberrantly spliced
env
mRNA species were found in the RSCh cells. Finally, we demonstrated that virus rescue efficiency can be significantly increased by complementation with the
env
gene and the highly expressed
gag
gene and can be increased the most by a helper virus infection. In summary, Env and Gag synthesis is increased after RSV-transformed hamster cell fusion with chicken fibroblasts, and both proteins provided in
trans
enhance RSV rescue. We conclude that the chicken fibroblast yields some factor(s) needed for RSV replication, particularly Env and Gag synthesis, in nonpermissive rodent cells.

IMPORTANCE
One of the important issues in retrovirus heterotransmission is related to cellular factors that prevent virus replication. Rous sarcoma virus (RSV), a member of the avian sarcoma and leukosis family of retroviruses, is able to infect and transform mammalian cells; however, such transformed cells do not produce infectious virus particles. Using the well-defined model of RSV-transformed rodent cells, we established that the lack of virus replication is due to the absence of chicken factor(s), which can be supplemented by cell fusion. Cell fusion with permissive chicken cells led to an increase in RNA splicing and nuclear export of specific viral mRNAs, as well as synthesis of respective viral proteins and production of virus-like particles. RSV rescue by cell fusion can be potentiated by in
trans
expression of viral genes in chicken cells. We conclude that rodent cells lack some chicken factor(s) required for proper viral RNA processing and viral protein synthesis.
A Conformational Transition Observed in Single HIV-1 Gag Molecules during
In Vitro
Assembly of Virus-Like Particles
Authors: Munro James B. , Nath Abhinav , Färber Michael , Datta Siddhartha A. K. , Rein Alan , Rhoades Elizabeth , Mothes Walther
Published: January 2014

The conformational changes within single HIV-1 Gag molecules that occur during assembly into immature viruses are poorly understood. Using an
in vitro
assembly assay, it has been proposed that HIV-1 Gag undergoes a conformational transition from a compact conformation in solution to an extended rod-like conformation in virus-like particles (VLPs). Here we used single-molecule Förster resonance energy transfer (smFRET) to test this model by directly probing the conformation of single HIV-1 Gag molecules. We demonstrate that monomeric HIV-1 Gag lacking the p6 domain and the N-terminal myristoyl moiety is found in solution predominantly in a compact conformation. Gag in this conformation, and in the presence of nucleic acid, assembles into 30-nm-diameter particles. However, with the addition of inositol hexakisphosphate, Gag adopts a linear conformation and assembles into full-sized ∼100-to-150-nm-diameter VLPs. Parallel fluorescence correlation spectroscopy measurements show that this conformational transition occurs early in the assembly process when Gag oligomers are small, perhaps as early as upon dimerization. Thus, smFRET measurements confirm that HIV-1 Gag transitions from a compact to a linear conformation during the formation of VLPs. Our results are consistent with a model whereby binding of HIV-1 Gag to phosphoinositides at the plasma membrane stabilizes an extended conformation and promotes oligomerization into the radially aligned immature capsid.

IMPORTANCE
The establishment of single-molecule fluorescence techniques reveals the conformational state of individual HIV-1 Gag molecules prior to and during
in vitro
assembly into virus-like particles. The data demonstrate that Gag in distinct conformations forms particles with different morphologies. In the compact conformation, in the presence of nucleic acid, Gag forms spherical particles of a diameter of approximately 30 nm. In the extended conformation, Gag forms spherical virus-like particles of approximately 100-nm diameter. The adoption of the extended conformation required the presence of inositol hexakisphosphate in addition to nucleic acid. Our results are consistent with a model whereby binding of HIV-1 Gag to phosphoinositides at the plasma membrane stabilizes an extended conformation and promotes oligomerization into the radially aligned immature capsid.
Induction of HIV-Blocking Anti-CCR5 IgA in Peyers's Patches without Histopathological Alterations
Authors: Pastori Claudia , Diomede Lorenzo , Venuti Assunta , Fisher Gregory , Jarvik Jonathan , Bomsel Morgane , Sanvito Francesca , Lopalco Lucia
Published: January 2014

The chemokine receptor CCR5 is essential for HIV infection and is thus a potential target for vaccine development. However, because CCR5 is a host protein, generation of anti-CCR5 antibodies requires the breaking of immune tolerance and thus carries the risk of autoimmune responses. In this study, performed in mice, we compared 3 different immunogens representing surface domains of murine CCR5, 4 different adjuvants, and 13 different immunization protocols, with the goal of eliciting HIV-blocking activity without inducing autoimmune dysfunction. In all cases the CCR5 sequences were presented as fusions to the Flock House virus (FHV) capsid precursor protein. We found that systemic immunization and mucosal boosting elicited CCR5-specific antibodies and achieved consistent priming in Peyer's patches, where most cells showed a phenotype corresponding to activated B cells and secreted high levels of IgA, representing up to one-third of the total HIV-blocking activity. Histopathological analysis revealed mild to moderate chronic inflammation in some tissues but failed in reporting signs of autoimmune dysfunction associated with immunizations. Antisera against immunogens representing the N terminus and extracellular loops 1 and 2 (Nter1 and ECL1 and ECL2) of CCR5 were generated. All showed specific anti-HIV activity, which was stronger in the anti-ECL1 and -ECL2 sera than in the anti-Nter sera. ECL1 and ECL2 antisera induced nearly complete long-lasting CCR5 downregulation of the receptor, and especially, their IgG-depleted fractions prevented HIV infection in neutralization and transcytosis assays. In conclusion, the ECL1 and ECL2 domains could offer a promising path to achieve significant anti-HIV activity
in vivo
.

IMPORTANCE
The study was the first to adopt a systematic strategy to compare the immunogenicities of all extracellular domains of the CCR5 molecule and to set optimal conditions leading to generation of specific antibodies in the mouse model. There were several relevant findings, which could be translated into human trials. (i) Prime (systemic) and boost (mucosal) immunization is the best protocol to induce anti-self antibodies with the expected properties. (ii) Aluminum is the best adjuvant in mice and thus can be easily used in nonhuman primates (NHP) and humans. (iii) The Flock House virus (FHV) system represents a valid delivery system, as the structure is well known and is not pathogenic for humans, and it is possible to introduce constrained regions able to elicit antibodies that recognize conformational epitopes. (iv) The best CCR5 vaccine candidate should include either extracellular loop 1 or 2 (ECL1 or ECL2), but not N terminus domains.
Symptomatic ileofemoral deep vein thrombosis due to May-Thurner syndrome
Authors: Alirhayim Zaid , El Atrache Mazen , Rocco Nicole , Drake Sean
Published: January 2014

A 33-year-old woman with no medical history reported an acute onset of left leg and thigh swelling. A review of her medications revealed that she had started oral contraceptives 2 months previously. Ultrasonography and subsequent venography demonstrated extensive ileofemoral clot burden. Thrombolysis and thrombectomy successfully restored venous return with subsequent improvement in the leg swelling and oedema. In this case, we describe a patient presenting with extensive ileofemoral deep vein thrombosis, otherwise known as the May-Thurner syndrome.
A mountain among molehills: removing an impinging large femoral neck osteochondroma in a man with hereditary multiple exostoses
Authors: Fitzgerald Conall W R , Rowan Fiachra E , O'Neill Shane C , Mulhall Kevin J
Published: January 2014

A 31-year-old man with a history of hereditary multiple exostoses (HME) presented with persistent right groin pain and reduced hip range of movement. Examination demonstrated a positive FADIR (flexion, adduction and internal rotation) test suggesting femoroacetabular impingement (FAI). Investigations showed multiple sessile osteochondromata of the right femur with a dominant anterolateral femoral neck osteochondroma causing flexion block. The patient underwent an uncomplicated proximal femoral exostectomy. Six-week postoperative pain, range of movement and daily activity had greatly improved. This case highlights that even in the setting of multiple osteochondromata, excellent impingement relief can be achieved following selective proximal femoral exostectomy.
Comparative effectiveness study on human papillomavirus detection methods used in the cervical cancer screening programme
Authors: Nygård Mari , Røysland Kjetil , Campbell Suzanne , Dillner Joakim
Published: January 2014

Objectives

To compare the short-term and long-term effectiveness of human papillomavirus (HPV) tests in Norwegian Cervical Cancer Screening Programme (NCCSP).

Design

Nationwide register-based prospective follow-up study.

Setting

In 2005, the NCCSP implemented HPV testing in follow-up of unsatisfactory, atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytology.

Participants

19 065 women with repeat cytology and HPV test after unsatisfactory ASC-US or LSIL screening result in 2005–2009.

Interventions

Through individual registry linkages we observed how women were treated in the regular medical care.

Main outcome measures

We estimated cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in 6 months and 3 years after repeat cytology and HPV test. Patients diagnosed with CIN2+ in 6 months and 3 years were assessed for initial HPV positivity.

Results

5392 had ASC-US/LSIL and 13 673 had normal/unsatisfactory repeat cytology; for HPV detection 4715 used AMPLICOR HPV Test (Roche Diagnostics, Basel, Switzerland), 9162 Hybrid Capture 2 (HC2) High-Risk HPV DNA Test (QIAGEN, Gaithersburg, Maryland, USA) and 5188 PreTect HPV-Proofer (NorChip, Klokkarstua, Norway). Among those with ASC-US/LSIL repeat cytology, 3-year risk of CIN2+ was 15-fold in Amplicor/HC2-positives compared with Amplicor/HC2-negatives and sevenfold in Proofer-positives compared with Proofer-negatives; a 3-year risk of CIN2+ was 2.1% (95% CI 0.7% to 3.4%) in Amplicor-negatives and 7.2% (95% CI 5.4% to 8.9%) in Proofer-negatives. Close to 100% of patients with CIN2+ diagnosed within 6 months tested positive to HPV (all methods). Considering all patients diagnosed with CIN2+ in 3-year follow-up, 97% were initially positive in the Amplicor group and more than 94% in the HC2 group, compared with less than 80% in the Proofer group.

Conclusions

While the long-term evaluation of new screening routines showed a good overall performance of triage-HPV DNA testing, the management of HPV-negative women with persistent ASC-US/LSIL was suboptimal.
The prognostic value of Ki67 in systemically untreated patients with node-negative breast cancer
Authors: Pathmanathan Nirmala , Balleine Rosemary L , Jayasinghe Upali W , Bilinski Kellie L , Provan Pamela J , Byth Karen , Bilous A Michael , Salisbury Elizabeth L , Boyages John
Published: January 2014

Aim

To evaluate the utility of Ki67 as a prognostic marker in a series of patients with node-negative breast cancer untreated with adjuvant systemic therapy.

Methods

The cohort consisted of 203 cases treated with breast conserving surgery and radiation only; median follow-up was 183 months (range 156–277 months). An immunohistochemical panel of oestrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK)5/6 and Ki67 and human epidermal growth factor 2 in situ hybridization (HER2-ISH) was performed on the tumour samples. Ki67 scores were evaluable in 193/203 patients (95.1%). The primary outcome was breast cancer specific survival (BCSS).

Results

Of the cohort, 29 (14.2%) died of breast cancer. A cut off of 10% separated tumours into a ‘Ki67-low’ (n=70) or ‘Ki67-high’ group (n=123). The breast cancer specific survival was 97.1% and 77.6% for Ki67-low and Ki67-high groups, respectively. Univariate analysis showed that in this lymph node-negative cohort, the predictors for BCSS were tumour size, Ki67, LVI, age and histological grade 3. Multivariable analysis showed that Ki67 index and lymphovascular space invasion were independent predictors of breast cancer death. To examine the utility of Ki67 in assignment of immunohistochemically molecular subtypes, cases were assigned into Luminal A (ER-positive, HER2-negative, Ki67 ≤14%), Luminal B (ER-positive, HER2-negative, Ki67 >14%) and triple negative (ER/PR-negative and HER2-negative, any Ki67). The 15-year breast cancer specific survival was 91.7%, 79.4% and 75.8%, respectively.

Conclusions

A statistically significant difference in breast cancer specific survival is seen in groups defined using Ki67 and receptor status, whereas histological grading was not a significant predictor of survival. Ki67 immunostaining provides prognostic information beyond traditionally assessed clinicopathological variables.
Stress-induced stimulation of choline transport in cultured choroid plexus epithelium exposed to low concentrations of cadmium
Authors: Young Robin K. , Villalobos Alice R. A.
Published: January 2014

The choroid plexus epithelium forms the blood-cerebrospinal fluid barrier and accumulates essential minerals and heavy metals. Choroid plexus is cited as being a “sink” for heavy metals and excess minerals, serving to minimize accumulation of these potentially toxic agents in the brain. An understanding of how low doses of contaminant metals might alter transport of other solutes in the choroid plexus is limited. Using primary cultures of epithelial cells isolated from neonatal rat choroid plexus, our objective was to characterize modulation of apical uptake of the model organic cation choline elicited by low concentrations of the contaminant metal cadmium (CdCl2). At 50–1,000 nM, cadmium did not directly decrease or increase 30-min apical uptake of 10 μM [3H]choline. However, extended exposure to 250–500 nM cadmium increased [3H]choline uptake by as much as 75% without marked cytotoxicity. In addition, cadmium induced heat shock protein 70 and heme oxygenase-1 protein expression and markedly induced metallothionein gene expression. The antioxidant N-acetylcysteine attenuated stimulation of choline uptake and induction of stress proteins. Conversely, an inhibitor of glutathione synthesis l-buthionine-sulfoximine (BSO) enhanced stimulation of choline uptake and induction of stress proteins. Cadmium also activated ERK1/2 MAP kinase. The MEK1 inhibitor PD98059 diminished ERK1/2 activation and attenuated stimulation of choline uptake. Furthermore, inhibition of ERK1/2 activation abated stimulation of choline uptake in cells exposed to cadmium with BSO. These data indicate that in the choroid plexus, exposure to low concentrations of cadmium may induce oxidative stress and consequently stimulate apical choline transport through activation of ERK1/2 MAP kinase.