bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of oxygen‐17 excess of nitrate and sulfate at sub‐micromole levels using the pyrolysis method
Authors: Geng Lei , Schauer Andrew J. , Kunasek Shelley A. , Sofen Eric D. , Erbland Joseph , Savarino Joël , Allman Daniel J. , Sletten Ronald S. , Alexander Becky
Published: October 2013

RATIONALE

The oxygen‐17 excess (Δ17O) of nitrate and sulfate contains valuable information regarding their atmospheric formation pathways. However, the current pyrolysis method to measure Δ17O requires large sample amounts (>4 µmol for nitrate and >1 µmol for sulfate). We present a new approach employing a Gas Bench interface which cryofocuses O2 produced from sample pyrolysis, enabling the analysis of sub‐micromole size samples.

METHODS

Silver nitrate or sulfate at sub‐micromole levels in a sample container was thermally decomposed to O2 and byproducts in a modified Temperature Conversion/Elemental Analyzer (TC/EA). Byproducts (mainly NO2 for silver nitrate and SO2 for silver sulfate) were removed in a liquid nitrogen trap and the sample O2 was carried by ultra‐pure helium (He) gas to a Gas Bench II interface where it was cryofocused prior to entering an isotope ratio mass spectrometer.

RESULTS

Analysis of the international nitrate reference material USGS35 (Δ17O = 21.6‰) within the size range of 300–1000 nmol O2 gave a mean Δ17O value of (21.6 ± 0.69) ‰ (mean ±1σ). Three inter‐laboratory calibrated sulfate reference materials, Sulf‐α, Sulf‐β and Sulf‐ε, each within the size range of 180–1000 nmol O2, were analyzed and shown to possess mean Δ17O values of (0.9 ± 0.10) ‰, (2.1 ± 0.25) ‰ and (7.0 ± 0.63) ‰, respectively.

CONCLUSIONS

The analyses of nitrate and sulfate reference materials at sub‐micromole levels gave Δ17O values consistent with their accepted values. This new approach of employing the Gas Bench to cryofocus O2 after the pyrolysis of AgNO3 and Ag2SO4 particularly benefits the effort of measuring Δ17O in sample types with a low abundance of nitrate and sulfate such as ice cores. Copyright © 2013 John Wiley & Sons, Ltd.
A membrane inlet mass spectrometry system for noble gases at natural abundances in gas and water samples
Authors: Visser Ate , Singleton Michael J. , Hillegonds Darren J. , Velsko Carol A. , Moran Jean E. , Esser Bradley K.
Published: October 2013

RATIONALE

Noble gases dissolved in groundwater can reveal paleotemperatures, recharge conditions, and precise travel times. The collection and analysis of noble gas samples are cumbersome, involving noble gas purification, cryogenic separation and static mass spectrometry. A quicker and more efficient sample analysis method is required for introduced tracer studies and laboratory experiments.

METHODS

A Noble Gas Membrane Inlet Mass Spectrometry (NG‐MIMS) system was developed to measure noble gases at natural abundances in gas and water samples. The NG‐MIMS system consists of a membrane inlet, a dry‐ice water trap, a carbon‐dioxide trap, two getters, a gate valve, a turbomolecular pump and a quadrupole mass spectrometer equipped with an electron multiplier. Noble gases isotopes 4He, 22Ne, 38Ar, 84Kr and 132Xe are measured every 10 s.

RESULTS

The NG‐MIMS system can reproduce measurements made on a traditional noble gas mass spectrometer system with precisions of 2%, 8%, 1%, 1% and 3% for He, Ne, Ar, Kr and Xe, respectively. Noble gas concentrations measured in an artificial recharge pond were used to monitor an introduced xenon tracer and to reconstruct temperature variations to within 2 °C. Additional experiments demonstrated the capability to measure noble gases in gas and in water samples, in real time.

CONCLUSIONS

The NG‐MIMS system is capable of providing analyses sufficiently accurate and precise for introduced noble gas tracers at managed aquifer recharge facilities, groundwater fingerprinting based on excess air and noble gas recharge temperature, and field and laboratory studies investigating ebullition and diffusive exchange. Copyright © 2013 John Wiley & Sons, Ltd.
Comprehensive analysis of neurotransmitters from regenerating planarian extract using an ultrahigh‐performance liquid chromatography/mass spectrometry/selected reaction monitoring method
Authors: Rangiah Kannan , Palakodeti Dasaradhi
Published: October 2013

RATIONALE

Absolute quantification of neurotransmitters (NTs) from biological systems is imperative to track how changes in concentration of active neurochemicals may affect biological behavior. A sensitive method for the absolute quantification of multiple NTs in a single method is highly needed.

METHODS

A stable‐isotope dilution ultrahigh‐performance liquid chromatography/mass spectrometry/selected reaction monitoring (UHPLC/MS/SRM) assay has been developed for a sensitive and quantitative assessment of NTs in planaria. We used this method for the simultaneous quantification of 16 NTs. All analytes showed a linear relationship between concentrations (0.78–50 ng/mL), regression coefficients higher than 0.97, accuracy (91–109%) and low coefficients of variation (CVs). The inter‐day CVs for the lowest quality controls (1.56 ng/mL) were in the range between 2–11%.

RESULTS

The levels of most of the NTs were similar in both sexual and asexual planarians except for glutamic acid, which was about two‐fold higher in asexual compared to sexual planarians. We identified high levels of serotonin and failed to detect tryptamine suggesting that the pathway essential for the conversion of tryptophan into tryptamine is absent in planarians. Interestingly, we also found high levels of dopamine and L‐DOPA in regenerating planarians suggesting their possible role in regeneration.

CONCLUSIONS

For the first time, we developed novel methodology based on UHPLC/MS/SRM and quantified 16 NTs with high sensitivity and specificity from sexual and asexual strains of planarian Schmidtea mediterranea. This method will also have great application in quantifying various NTs with great precision in different model systems. Copyright © 2013 John Wiley & Sons, Ltd.
A novel Cookson‐type reagent for enhancing sensitivity and specificity in assessment of infant vitamin D status using liquid chromatography/tandem mass spectrometry
Authors: Ogawa Shoujiro , Ooki Satoshi , Morohashi Misato , Yamagata Kenichiro , Higashi Tatsuya
Published: October 2013

RATIONALE

25‐Hydroxyvitamin D3 [25(OH)D3] is the best‐established indicator of vitamin D status. 4‐Phenyl‐1,2,4‐triazoline‐3,5‐dione (PTAD), a representative Cookson‐type reagent, has often been employed for enhancing the sensitivity in the trace determination of 25(OH)D3 in a neonatal dried blood spot (DBS), which contains only 2.65 μL of whole blood, using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS). The objective of this study was the development of a novel Cookson‐type reagent surpassing PTAD in terms of sensitivity and specificity in the LC/ESI‐MS/MS assay of 25(OH)D3.

METHODS

A novel Cookson‐type reagent, 4‐(4'‐dimethylaminophenyl)‐1,2,4‐triazoline‐3,5‐dione (DAPTAD), was synthesized from 4‐dimethylaminobenzoyl chloride. The DAPTAD‐derivative of 25(OH)D3 was prepared and its LC/ESI‐MS/MS behavior was examined. The applicability of the DAPTAD‐derivatization in the determination of 25(OH)D3 in neonatal DBSs was also examined.

RESULTS

The derivatization was completed at room temperature within 1 h. The DAPTAD‐derivative of 25(OH)D3 provided a characteristic product ion derived from the cleavage of the vitamin D skeleton during MS/MS. The limit of detection of the DAPTAD‐derivative during selected reaction monitoring was 0.25 fmol on the column, which was 30 and 2 times lower than those of the intact 25(OH)D3 and the PTAD‐derivative, respectively. The DAPTAD‐derivatization followed by LC/ESI‐MS/MS enabled the detection of a trace amount (in the low‐ng/mL range) of 25(OH)D3 in DBSs with a simple pretreatment (only methanol extraction) and short chromatographic run time (10 min). The DAPTAD‐derivatization was also useful for the separation of 25(OH)D3 from a potent interfering metabolite, 3‐epi‐25‐hydroxyvitamin D3 [3‐epi‐25(OH)D3]. On the contrary, the assay using the PTAD‐derivatization might lead to overestimation of the true 25(OH)D3 levels due to the co‐elution of 25(OH)D3 and 3‐epi‐25(OH)D3.

CONCLUSIONS

We developed DAPTAD for enhancing the sensitivity and specificity of the LC/ESI‐MS/MS assay of 25(OH)D3. Our new method using DAPTAD can reduce the overestimation of the 25(OH)D3 levels, and will prove helpful in the diagnosis of vitamin D deficiency in infants. Copyright © 2013 John Wiley & Sons, Ltd.
Development of a liquid chromatography/tandem mass spectrometry method to investigate the presence of biomarkers of DNA damage in urine related to red meat consumption and risk of colorectal cancer
Authors: Da Pieve Chiara , Sahgal Natasha , Moore Sharon A. , Velasco‐Garcia Maria N.
Published: October 2013

RATIONALE

The consumption of red meat is known to enhance the endogenous formation of N‐nitroso compounds (NOCs), which are potent carcinogens. DNA damage related to NOCs, and hence red meat, has been detected in colorectal cells and in blood. We proposed to extend previous studies to a non‐invasive approach for the detection of O6‐carboxymethylguanine (O6CMG) and O6‐carboxymethyl‐2'‐deoxyguanosine (O6CMdG) in urine in relation to red meat intake using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The presence of the adduct in urine samples either as the free base or as 2'‐deoxynucleoside could help in determining the repair mechanism involved when such lesions are produced. A non‐invasive assessment of DNA adducts could also allow for large‐scale analyses in the population and cancer prevention dietary strategies.

METHODS

An LC/MS/MS method for the quantitation of O6CMG and O6CMdG was developed. Urine samples collected from healthy volunteers on red meat and vegetarian diets were analysed either by direct injection or after purification by solid‐phase extraction (SPE). A separate LC/MS/MS method for O6‐methylguanine (O6MeG) and O6‐methyl‐2'‐deoxyguanosine (O6MedG), which are possible hydrolysis products forming during the sample pre‐treatment, was also developed.

RESULTS

The developed LC/MS/MS method allowed the simultaneous measurement of O6CMG and O6CMdG. The limits of detection (LODs) were 0.38 ng/mL for O6CMG and 0.18 ng/mL for O6CMdG. The direct injection analysis of the clinical samples showed low sensitivity due to high background signal that was improved by SPE purification. However, the concentrations of the adducts in clinical samples were still found to be below the LOD.

CONCLUSIONS

Novel, reproducible, and accurate LC/MS/MS methods were developed for the determination of the urinary content of O6CMG and O6CMdG, and of the possible formation of O6MeG and O6MedG by decarboxylation. Clinical samples from volunteers on different diets were analysed. Further studies are required to discover a link between the presence of these biomarkers in urine and red meat consumption. Copyright © 2013 John Wiley & Sons, Ltd.
What's Love Got to Do with It: Relationship Functioning and Mental and Physical Quality of Life Among Pregnant Adolescent Couples
Authors: Kershaw Trace , Murphy Alexandrea , Divney Anna , Magriples Urania , Niccolai Linda , Gordon Derrick
Published: October 2013

The study objective was to describe relationship adjustment and its association with mental and physical quality of life for young couples expecting a baby. 296 young pregnant couples recruited from urban obstetric clinics reported on relationship strengths (e.g., equity, romantic love, and attractiveness), relationship risks (e.g., attachment, intimate partner violence), external family support, relationship adjustment, and mental and physical quality of life. Using the Actor Partner Interdependence Model we assessed both actor and partner effects of relationship variables on relationship adjustment and quality of life. Sixty‐one percent of couples had at least one member with moderate or severe relationship distress. Lower attachment avoidance, lower attachment anxiety, higher relationship equity, lack of intimate partner violence, feelings of love, perceived partner attractiveness, and family support of the relationship related to better relationship adjustment. Associations were fairly consistent across gender. Better relationship adjustment related to more positive mental and physical quality of life for both young women and men. Our results highlight the potential importance of strong relationships on the well‐being of expecting parents. Our results suggest that secure attachments, equitable relationships, feelings of love, and a lack of violence may be particularly important in having strong relationships and improved mental and physical health during pregnancy.
Rise of Pilgrims on the Camino to Santiago: Sign of Change or Religious Revival?
Authors: Oviedo Lluis , de Courcier Scarlett , Farias Miguel
Published: October 2013

There is a renewed interest amongst scholars in the practice of pilgrimage. Over the past two decades, pilgrim numbers have risen significantly, whilst forms of “implicit” or “alternative” spirituality have gained visibility and now coexist with organised religions, sometimes sharing the same ritualistic space. There is probably no better place to look at the coexistence of old and new forms of ritual expression than in the Camino to Santiago. To better understand the meanings attributed to this pilgrimage, we undertook a survey with over 470 pilgrims at various locations along the Camino. The findings confirm that individuals with various, often contrasting, motivations and expectations walk side by side on this pilgrimage route. We suggest that the results cannot be read simplistically as either confirming a “post-secularisation” trend or a religious revival.
Research skills: the neglected competency in tomorrow’s 21st-century
doctors
Authors: Abu-Zaid Ahmed
Published: October 2013

None
Extremal domains of big volume for the first eigenvalue of the Laplace–Beltrami operator in a compact manifold
Authors: Sicbaldi Pieralberto
Published: October 2013

We prove the existence of new extremal domains for the first eigenvalue of the Laplace–Beltrami operator in some compact Riemannian manifolds of dimension

n⩾2

. The volume of such domains is close to the volume of the manifold. If the first eigenfunction

\phi _{0}

of the Laplace–Beltrami operator over the manifold is a nonconstant function, these domains are close to the complement of geodesic balls centered at a nondegenerate critical point of

\phi _{0}

. If

\phi _{0}

is a constant function and

n⩾4

, these domains are close to the complement of geodesic balls centered at a nondegenerate critical point of the scalar curvature.
Carvajal marca la diferencia: nuevo posicionamiento de marca como símbolo de transformación organizacional
Authors: Rengifo Mera Mónica , Manfredi Luciana
Published: October 2013

El presente caso de estudio tiene por objetivo consolidar el proceso de redefinición de la arquitectura de lamarca Carvajal y la de sus empresas, a través del cual busca convertirse en un conglomerado competitivoen entornos exigentes, atraer nuevos inversionistas y posicionarse como una multinacional que generavalor para sus accionistas. Lo anterior implica la refocalización y la rentabilización de sus actuales negociosen las diferentes geografías, de la mano con un cambio de marca que refleje esa transformación y fortalezcasu posicionamiento en el mercado global. El presente estudio está basado en entrevistas en profundidad yfuentes secundarias compuestas por datos de la organización y estudios que fueron realizados por firmasconsultoras contratadas por la Carvajal.
Paleoenvironmental implications of carbon stable isotope composition of land snail tissues
Authors: Yanes Yurena , Asta María P. , Ibáñez Miguel , Alonso María R. , Romanek Christopher S.
Published: October 2013

Land snail shell δ13C value is often used as a paleovegetation proxy assuming that snails ingest all plants in relation to their abundance, and that plants are the only source of carbon. However, carbonate ingestion and variable metabolic rates complicate these relationships. We evaluate if live-collected snails from Lanzarote (Canary Islands) reflect the abundance of C3 and CAM plants. Snails were collected on either CAM or C3 plants for isotope analysis of shell and body, and shell size. Respective shell and body δ13C values of snails collected on CAM plants averaged − 8.5 ± 1.7‰ and − 22.8 ± 1.6‰, whereas specimens from C3 plants averaged − 10.1 ± 0.7‰ and − 24.9 ± 1.1‰. A flux balance model suggests snails experienced comparable metabolic rates. A two-source mass balance equation implies that snails consumed ~ 10% of CAM, which agrees with their abundance in the landscape. Snails collected on CAM plant were smaller than those on C3 plants. Conclusively: 1) snails consume CAM plants when they are available; 2) migration of snails among C3 and CAM plants is a common phenomenon; and 3) C3 plants may be a more energetic food for growth than CAM plants. This study shows that shell δ13C values offer approximate estimates of plants in C3–CAM mixed environments.
Erfahrungen und Umgang der Pflegenden mit aggressivem Verhalten von Bewohner(inne)n: eine deskriptive Querschnittstudie in Schweizer Pflegeheimen
Authors: Zeller Adelheid , Needham Ian , Dassen Theo , Kok Gerjo , Halfens Ruud J. G.
Published: October 2013

Die vorliegende deskriptiv-explorative Querschnittstudie, an der 814 Pflegende (51.8 %) aus 21 Schweizer Alters- und Pflegeheimen teilnahmen, gibt einen Einblick in die Erfahrungen und den Umgang mit aggressivem Verhalten der Bewohner(innen). Zudem wurde die Belastung aggressiven Verhaltens auf die Pflegenden und die Auswirkungen auf die Beziehung zwischen Pflegenden und Bewohner(inne)n erfasst. Die Befragung wurde mithilfe eines validierten Fragebogens durchgeführt. Rund 38 % der Pflegenden haben in den letzten sieben Arbeitstagen vor der Datenerhebung Aggressionsereignisse erlebt. In den meisten Fällen ging die Aggression von Bewohner(inne)n aus, die an Demenz und/oder Depression litten und trat während einer pflegerischen Tätigkeit mit Körperkontakt auf. Als Auslöser vermuteten die Teilnehmenden in erster Linie das «Nichtverstehen» und die «Überforderung» der Bewohner(innen). Ein «beruhigendes Gespräch» und «Distanz einnehmen» wurde am häufigsten eingesetzt, um die Situation zu beruhigen. Rund 40 % der Teilnehmenden empfinden körperliche Angriffe als belastend und etwa 23 % haben Angst, vor allem, wenn aggressives Verhalten ohne Vorwarnung auftritt. Rund 4 % der Pflegenden vermeiden anschließend häufig oder immer den Kontakt zu den betreffenden Bewohner(inne)n und 12.3 % erleben eine Störung in der Beziehung. Es ist zu vermuten, dass die Pflegenden die Emotionen der Bewohner(innen), die dem aggressiven Verhalten zugrunde liegen, in der akuten Phase der Eskalation unzureichend erfassen sowie mögliche Frühwarnzeichen beginnender Aggression spät oder nicht erkennen.
Entwicklung, Umsetzung und Evaluation pflegerischer Interventionen für Menschen mit Demenz in der stationären Altenhilfe in Deutschland – eine Literaturstudie
Authors: Palm Rebecca , Köhler Kerstin , Dichter Martin Nikolaus , Bartholomeyczik Sabine , Holle Bernhard
Published: October 2013

Seit 2007 liegen Rahmenempfehlungen für die Pflege von Menschen mit Demenz, insbesondere für den Umgang mit herausforderndem Verhalten, in der stationären Altenhilfe vor. Ziel der vorliegenden Arbeit ist eine systematische Übersicht über abgeschlossene Projekte zur Entwicklung, Umsetzung und Evaluation empfohlener pflegerischer Interventionen in deutschen Altenpflegeeinrichtungen. Mittels systematischer Literaturrecherche wurden 22 Veröffentlichungen aus 8 Projekten identifiziert und ausgewertet. Die Auswertung erfolgte kriteriengestützt in Anlehnung an die CReDECI-Kriterien zur Berichterstattung von komplexen Interventionen. Die Veröffentlichungen beschreiben die Umsetzung von Erinnerungspflege und Snoezelen, die Anwendung von Dementia Care Mapping (DCM) sowie von verstehender Diagnostik und Assessmentinstrumenten. Alle Interventionen enthielten trotz zum Teil ähnlicher theoretischer Fundierung und Zielsetzung unterschiedliche Komponenten. Die Implementierung erforderte hohen Schulungsbedarf und eine enge Begleitung und Unterstützung durch die Projektverantwortlichen. Eine Prozessevaluation sowie eine Berichterstattung über die Anpassung der Interventionen an vorherrschende Rahmenbedingungen lagen nur bei wenigen Projekten vor. Zum Teil fehlen in den Veröffentlichungen wichtige Informationen, die zur Anwendung in der Praxis und in weiterführenden Studien von großer Relevanz sind.
Die Implementierung von Bezugspflege im intensivpflegerischen Setting – Evaluation mit dem Instrument zur Erfassung von Pflegesystemen (IzEP)
Authors: Fröhlich Martin R. , Becker Christiane , Handel Elisabeth , Spirig Rebecca
Published: October 2013

Der Schwerpunkt der Bezugspflege am UniversitätsSpital Zürich (USZ) liegt auf der Verantwortung einer Pflegefachperson für den Pflegeprozess der von ihr betreuten Patient(inn)en. Dieser wird im Rahmen einer professionellen Beziehung mit der damit verbundenen Verantwortlichkeit für pflegerische Entscheidungen und Handlungen sowie gestützt auf forschungs- und erfahrungsbasiertes Fachwissen gestaltet – vom Tag der Aufnahme bis zur Entlassung aus dem Spital. Der Artikel beschreibt die Evaluation der Pflegeorganisationsform auf drei Intensivabteilungen am USZ im Kontext der Implementierung der Bezugspflege mit dem Instrument zur Erfassung von Pflegesystemen (IzEP©). In einem Vorher-nachher-Vergleich zeigte IzEP© bei der Umsetzung von Konzeptinhalten im Intensivpflegebereich eine klare Steigerung pflegerischer Kontinuität und Patient(inn)enorientierung von anfänglich 56 – 60 % auf Werte von 68 – 75 % (Score von 0 – 100 %). Zugleich wurde vorhandenes Entwicklungspotenzial für dieses Pflegesystem sichtbar. Es wurde deutlich, dass IzEP© aufgrund seines Aufbaus für einen breiten stationären Anwendungsbereich und in der Formulierung der Fragen auf idealtypische Pflegeorganisationsformen ausgerichtet ist. Gegebene Rahmenbedingungen des intensivpflegerischen Settings und spezifische Konzeptideen werden nur bedingt berücksichtigt. Somit bietet es einen eingeschränkten Wiedererkennungswert des eigenen Konzepts für die Befragungsgruppen.
Albuminurie beim Diabetiker: praktisches Management
Authors: Kistler Andreas D.
Published: October 2013

Die diabetische Nephropathie ist in der entwickelten Welt die häufigste Ursache eines dialysepflichtigen Nierenversagens. Eine erhöhte Albuminausscheidung im Urin ist charakteristisch für eine diabetische Nierenschädigung. Regelmässiges Mikroalbuminurie-Screening ermöglicht Früherkennung und frühzeitige Intervention. Bei manifester diabetischer Nephropathie dient eine Quantifizierung der Albuminurie der Verlaufsbeobachtung. Therapeutische Interventionen, die die Albuminurie zu reduzieren vermögen, verlangsamen die Progression einer diabetischen Nierenschädigung und reduzieren überdies die kardiovaskuläre Mortalität, da die Albuminurie einen unabhängigen kardiovaskulären Risikofaktor darstellt. Diese Übersichtsarbeit beschreibt den klassischen Verlauf der diabetischen Nephropathie und bespricht praxisrelevante Aspekte bei der Bestimmung der Albuminurie. Verfügbare prophylaktische und therapeutische Interventionen, allen voran Blutzuckerkontrolle und Hemmung des Renin-Angiotensin-Aldosteron-Systems, werden in einer evidenzbasierten Weise diskutiert.
Miktionsbeschwerden beim Mann: Differenzialdiagnosen und Therapie des benignen Prostatasyndroms
Authors: Meyer Daniel , Schmid Hans-Peter
Published: October 2013

Miktionsbeschwerden des Mannes treten in den meisten Fällen im Rahmen eines benignen Prostatasyndroms auf. Dennoch bedarf es einer korrekten Diagnostik zum Ausschluss anderer Pathologien. Neben neurogenen Ursachen können so andere urologische Differenzialdiagnosen abgeklärt und behandelt werden. Bestätigt sich die Diagnose des benignen Prostatasyndroms, stehen verschiedene medikamentöse und chirurgische Therapieoptionen zur Verfügung.
The social structure of microbial community involved in colonization resistance
Authors: He Xuesong , McLean Jeffrey S , Guo Lihong , Lux Renate , Shi Wenyuan
Published: October 2013

It is well established that host-associated microbial communities can interfere with the colonization and establishment of microbes of foreign origins, a phenomenon often referred to as bacterial interference or colonization resistance. However, due to the complexity of the indigenous microbiota, it has been extremely difficult to elucidate the community colonization resistance mechanisms and identify the bacterial species involved. In a recent study, we have established an in vitro mice oral microbial community (O-mix) and demonstrated its colonization resistance against an Escherichia coli strain of mice gut origin. In this study, we further analyzed the community structure of the O-mix by using a dilution/regrowth approach and identified the bacterial species involved in colonization resistance against E. coli. Our results revealed that, within the O-mix there were three different types of bacterial species forming unique social structure. They act as ‘Sensor’, ‘Mediator’ and ‘Killer’, respectively, and have coordinated roles in initiating the antagonistic action and preventing the integration of E. coli. The functional role of each identified bacterial species was further confirmed by E. coli-specific responsiveness of the synthetic communities composed of different combination of the identified players. The study reveals for the first time the sophisticated structural and functional organization of a colonization resistance pathway within a microbial community. Furthermore, our results emphasize the importance of ‘Facilitation’ or positive interactions in the development of community-level functions, such as colonization resistance.
The paradox of enrichment in phytoplankton by induced competitive interactions
Authors: Tubay Jerrold M. , Ito Hiromu , Uehara Takashi , Kakishima Satoshi , Morita Satoru , Togashi Tatsuya , Tainaka Kei-ichi , Niraula Mohan P. , Casareto Beatriz E. , Suzuki Yoshimi , Yoshimura Jin
Published: October 2013

The biodiversity loss of phytoplankton with eutrophication has been reported in many aquatic ecosystems, e.g., water pollution and red tides. This phenomenon seems similar, but different from the paradox of enrichment via trophic interactions, e.g., predator-prey systems. We here propose the paradox of enrichment by induced competitive interactions using multiple contact process (a lattice Lotka-Volterra competition model). Simulation results demonstrate how eutrophication invokes more competitions in a competitive ecosystem resulting in the loss of phytoplankton diversity in ecological time. The paradox is enhanced under local interactions, indicating that the limited dispersal of phytoplankton reduces interspecific competition greatly. Thus, the paradox of enrichment appears when eutrophication destroys an ecosystem either by elevated interspecific competition within a trophic level and/or destabilization by trophic interactions. Unless eutrophication due to human activities is ceased, the world's aquatic ecosystems will be at risk.
Three-dimensional Imaging of Crystalline Inclusions Embedded in Intact Maize Stalks
Authors: Badger John , Lal Jyotsana , Harder Ross , Inouye Hideyo , Gleber S. Charlotte , Vogt Stefan , Robinson Ian , Makowski Lee
Published: October 2013

Mineral inclusions in biomass are attracting increased scrutiny due to their potential impact on processing methods designed to provide renewable feedstocks for the production of chemicals and fuels. These inclusions are often sculpted by the plant into shapes required to support functional roles that include the storage of specific elements, strengthening of the plant structure and providing a defense against pathogens and herbivores.In situcharacterization of these inclusions faces substantial challenges since they are embedded in an opaque, complex polymeric matrix. Here we describe the use of Bragg coherent diffraction imaging (BCDI) to study mineral inclusions within intact maize stalks. Three-dimensional BCDI data sets were collected and used to reconstruct images of mineral inclusions at 50–100 nm resolution. Asymmetries in the intensity distributions around the Bragg peaks provided detailed information about the deformation fields within these crystal particles revealing lattice defects that result in distinct internal crystal domains.
Tools for Grouping Chemicals and Forming Categories
Authors: Madden J. C.
Published: October 2013

The purpose of this chapter is to provide an overview of the tools that are available to aid the grouping of chemicals into categories. The chapter describes not only bespoke tools (such as the OECD QSAR Toolbox and HESS) specifically designed for this purpose, but also includes more general tools that can be used to identify similar compounds (such as the Toxmatch software). These tools are discussed in the context of how they can be applied, that is for grouping chemicals based on common molecular initiating events or on structural similarities. Use of software to develop user­designed flexible workflows (such as the KNIME software) is also discussed.
Sources of Chemical Information, Toxicity Data and Assessment of Their Quality
Authors: Madden J. C.
Published: October 2013

This chapter identifies a range of sources that provide toxicity data that may be of use in category formation and read­across. Data in this context relate to both the chemical identity and characteristics of molecules in addition to biological (toxicological) information. Different methods of representing chemicals are given and caveats associated with the use of certain representations are also indicated. A glossary of key terms relating to assessment of data quality is provided along with guidance on methods to perform data quality assessment.
Category Formation Case Studies
Authors: Enoch S J , Przybylak K. R. , Cronin M. T. D.
Published: October 2013

This chapter outlines a series of case studies for chemical category formation and read­across. The main focus being around the use of mechanistic information related to the molecular initiating event encoded as in silico profilers in tools such as the OECD QSAR Toolbox. The chapter also outlines an example of the use of 2D chemical similarity in the formation of categories using freely available tools such as Toxmatch. All of the examples, including the associated data, use freely available computational tools and data.
Evaluation of Categories and Read-Across for Toxicity Prediction Allowing for Regulatory Acceptance
Authors: Cronin M. T. D.
Published: October 2013

This chapter describes the approaches to evaluate a read­across prediction and document it sufficient for regulatory acceptance e.g. for REACH. It defines the criteria that must be addressed in order to assess the confidence of such a prediction. These are the robustness of the category and the strength of the evidence associated with read­across. There is no rigid framework to evaluate and apply confidence to a prediction, but evidence must be provided to assure regulatory acceptance. The documentation to support such a prediction is described, as are the available training, guidance and education needs in this area.
CACTA-like transposable element in
ZmCCT
attenuated photoperiod sensitivity and accelerated the postdomestication spread of maize
Authors: Yang Qin , Li Zhi , Li Wenqiang , Ku Lixia , Wang Chao , Ye Jianrong , Li Kun , Yang Ning , Li Yipu , Zhong Tao , Li Jiansheng , Chen Yanhui , Yan Jianbing , Yang Xiaohong , Xu Mingliang
Published: October 2013

Significance

Maize was domesticated from teosinte in Southern Mexico roughly 9,000 years ago. Maize originally was sensitive to photoperiod and required short-day conditions to flower. Thus, the reduced sensitivity to photoperiod is prerequisite for maize spread to long-day temperate regions. A gene encoding a CCT domain-containing protein,
ZmCCT
, was found by many researchers to modulate photoperiod sensitivity. The current study shows that insertion of a CACTA-like transposon into the
ZmCCT
promoter can suppress the
ZmCCT
expression remarkably and thus attenuates maize sensitivity under long-day conditions. The transposable element (TE) insertion event occurred in a tropical maize plant and has been selected for and accumulated as maize adapted to vast long-day environments. This selection leaves behind a TE-related linkage disequilibrium block with the very-low-nucleotide variations.
Kindlin-3 regulates integrin activation and adhesion reinforcement of effector T cells
Authors: Moretti Federico A. , Moser Markus , Lyck Ruth , Abadier Michael , Ruppert Raphael , Engelhardt Britta , Fässler Reinhard
Published: October 2013

Significance

T cells use integrins for adhesion to endothelial cells and extravasation. Thus, their blocking with Abs prevents T cell extravasation and ameliorates autoimmune diseases, such as multiple sclerosis (MS). Given the side effects of these Abs, we explored the integrin activator Kindlin-3 as potential therapeutic target. Mice lacking Kindlin-3 in T cells were immunized with an autoantigen to induce experimental autoimmune encephalitis (EAE), a model of MS. Although these mice developed EAE, adoptively transferred autoreactive T cells from Kindlin-3–deficient mice to healthy recipients failed to induce EAE. We found that autoreactive Kindlin-3–null T cells extravasate only when the brain microvasculature expresses high integrin ligand levels. Thus, blockage of Kindlin-3 is not a viable alternative approach to treating MS.
Domain‐specific physical activity and health‐related quality of life in university students
Authors: Pedišić Željko , Rakovac Marija , Titze Sylvia , Jurakić Danijel , Oja Pekka
Published: October 2013

Information on the relationship between domain‐specific physical activity (PA) and health‐related quality of life (HRQoL) in the general population and specific groups is still scarce. The aim of this study was to determine the relationship between PA in work, transport, domestic and leisure‐time domains and HRQoL among university students. PA and HRQoL were assessed in a random stratified sample of 1750 university students using the International Physical Activity Questionnaire – long form and 12‐item Short Form Health Survey, respectively. The Spearman's rank correlations, adjusted for age, community size, personal monthly budget, body mass index, smoking habits and alcohol intake ranged from −0.11 to 0.18 in female students and −0.29 to 0.19 in male students. Leisure‐time, domestic, transport‐related PA and total PA were positively related to HRQoL. Inverse correlations with HRQoL were only found for work‐related PA in male students. Multiple linear regression analysis showed that only leisure‐time PA was related to the Physical Summary Component score (β = 0.08 for females and β = 0.10 for males, P < 0.05). Domain‐specific PA levels were not significantly related to the Mental Component Summary score. To get a more comprehensive insight in the relationship between PA and HRQoL, future studies should not only analyse total PA levels but also domain‐specific PA levels. The evidence on the positive relationship of leisure‐time, transport and domestic PA with HRQoL can potentially be used to support evidence‐based promotion of PA in a university setting, and as a hypothesis for future longitudinal studies on such potential causal relationships.
Supervillin binding to myosin II and synergism with anillin are required for cytokinesis
Authors: Smith Tara C. , Fridy Peter C. , Li Yinyin , Basil Shruti , Arjun Sneha , Friesen Ryan M. , Leszyk John , Chait Brian T. , Rout Michael P. , Luna Elizabeth J.
Published: October 2013

Cytokinesis, the process by which cytoplasm is apportioned between dividing daughter cells, requires coordination of myosin II function, membrane trafficking, and central spindle organization. Most known regulators act during late cytokinesis; a few, including the myosin II–binding proteins anillin and supervillin, act earlier. Anillin's role in scaffolding the membrane cortex with the central spindle is well established, but the mechanism of supervillin action is relatively uncharacterized. We show here that two regions within supervillin affect cell division: residues 831–1281, which bind central spindle proteins, and residues 1–170, which bind the myosin II heavy chain (MHC) and the long form of myosin light-chain kinase. MHC binding is required to rescue supervillin deficiency, and mutagenesis of this site creates a dominant-negative phenotype. Supervillin concentrates activated and total myosin II at the furrow, and simultaneous knockdown of supervillin and anillin additively increases cell division failure. Knockdown of either protein causes mislocalization of the other, and endogenous anillin increases upon supervillin knockdown. Proteomic identification of interaction partners recovered using a high-affinity green fluorescent protein nanobody suggests that supervillin and anillin regulate the myosin II and actin cortical cytoskeletons through separate pathways. We conclude that supervillin and anillin play complementary roles during vertebrate cytokinesis.
Key events during the transition from rapid growth to quiescence in budding yeast require posttranscriptional regulators
Authors: Li Lihong , Miles Shawna , Melville Zephan , Prasad Amalthiya , Bradley Graham , Breeden Linda L.
Published: October 2013

Yeast that naturally exhaust the glucose from their environment differentiate into three distinct cell types distinguishable by flow cytometry. Among these is a quiescent (Q) population, which is so named because of its uniform but readily reversed G1 arrest, its fortified cell walls, heat tolerance, and longevity. Daughter cells predominate in Q-cell populations and are the longest lived. The events that differentiate Q cells from nonquiescent (nonQ) cells are initiated within hours of the diauxic shift, when cells have scavenged all the glucose from the media. These include highly asymmetric cell divisions, which give rise to very small daughter cells. These daughters modify their cell walls by Sed1- and Ecm33-dependent and dithiothreitol-sensitive mechanisms that enhance Q-cell thermotolerance. Ssd1 speeds Q-cell wall assembly and enables mother cells to enter this state. Ssd1 and the related mRNA-binding protein Mpt5 play critical overlapping roles in Q-cell formation and longevity. These proteins deliver mRNAs to P-bodies, and at least one P-body component, Lsm1, also plays a unique role in Q-cell longevity. Cells lacking Lsm1 and Ssd1 or Mpt5 lose viability under these conditions and fail to enter the quiescent state. We conclude that posttranscriptional regulation of mRNAs plays a crucial role in the transition in and out of quiescence.
mTOR regulates phagosome and entotic vacuole fission
Authors: Krajcovic Matej , Krishna Shefali , Akkari Leila , Joyce Johanna A. , Overholtzer Michael
Published: October 2013

Macroendocytic vacuoles formed by phagocytosis, or the live-cell engulfment program entosis, undergo sequential steps of maturation, leading to the fusion of lysosomes that digest internalized cargo. After cargo digestion, nutrients must be exported to the cytosol, and vacuole membranes must be processed by mechanisms that remain poorly defined. Here we find that phagosomes and entotic vacuoles undergo a late maturation step characterized by fission, which redistributes vacuolar contents into lysosomal networks. Vacuole fission is regulated by the serine/threonine protein kinase mammalian target of rapamycin complex 1 (mTORC1), which localizes to vacuole membranes surrounding engulfed cells. Degrading engulfed cells supply engulfing cells with amino acids that are used in translation, and rescue cell survival and mTORC1 activity in starved macrophages and tumor cells. These data identify a late stage of phagocytosis and entosis that involves processing of large vacuoles by mTOR-regulated membrane fission.
The tethering complex HOPS catalyzes assembly of the soluble SNARE Vam7 into fusogenic trans-SNARE complexes
Authors: Zick Michael , Wickner William
Published: October 2013

The fusion of yeast vacuolar membranes depends on the disassembly of cis–soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complexes and the subsequent reassembly of new SNARE complexes in trans. The disassembly of cis-SNARE complexes by Sec17/Sec18p releases the soluble SNARE Vam7p from vacuolar membranes. Consequently, Vam7p needs to be recruited to the membrane at future sites of fusion to allow the formation of trans-SNARE complexes. The multisubunit tethering homotypic fusion and vacuole protein sorting (HOPS) complex, which is essential for the fusion of vacuolar membranes, was previously shown to have direct affinity for Vam7p. The functional significance of this interaction, however, has been unclear. Using a fully reconstituted in vitro fusion reaction, we now show that HOPS facilitates membrane fusion by recruiting Vam7p for fusion. In the presence of HOPS, unlike with other tethering agents, very low levels of added Vam7p suffice to induce vigorous fusion. This is a specific recruitment of Vam7p rather than an indirect stimulation of SNARE complex formation through tethering, as HOPS does not facilitate fusion with a low amount of a soluble form of another vacuolar SNARE, Vti1p. Our findings establish yet another function among the multiple tasks that HOPS performs to catalyze the fusion of yeast vacuoles.
SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress
Authors: Kassner Ingrid , Andersson Anneli , Fey Monika , Tomas Martin , Ferrando-May Elisa , Hottiger Michael O.
Published: October 2013

ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is localized in the nucleus, where it ADP-ribosylates specific target proteins. The post-translational modification (PTM) with a single ADP-ribose unit or with polymeric ADP-ribose (PAR) chains regulates protein function as well as protein–protein interactions and is implicated in many biological processes and diseases. SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine monomethylation of histones, but also methylates many non-histone target proteins such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that is methylated at K508
in vitro
and
in vivo
. ARTD1 auto-modification inhibits its methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the synthesis of PAR upon oxidative stress
in vivo
. Furthermore, laser irradiation-induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9-dependent manner. Together, these results reveal a novel mechanism for the regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation upon cellular stress.
Structure of a bacterial putative acetyltransferase defines the fold of the human
O
-GlcNAcase C-terminal domain
Authors: Rao Francesco V. , Schüttelkopf Alexander W. , Dorfmueller Helge C. , Ferenbach Andrew T. , Navratilova Iva , van Aalten Daan M. F.
Published: October 2013

The dynamic modification of proteins by
O
-linked
N
-acetylglucosamine (
O
-GlcNAc) is an essential posttranslational modification present in higher eukaryotes. Removal of
O
-GlcNAc is catalysed by
O
-GlcNAcase, a multi-domain enzyme that has been reported to be bifunctional, possessing both glycoside hydrolase and histone acetyltransferase (AT) activity. Insights into the mechanism, protein substrate recognition and inhibition of the hydrolase domain of human OGA (hOGA) have been obtained via the use of the structures of bacterial homologues. However, the molecular basis of AT activity of OGA, which has only been reported
in vitro
, is not presently understood. Here, we describe the crystal structure of a putative acetyltransferase (
Og
pAT) that we identified in the genome of the marine bacterium
Oceanicola granulosus
, showing homology to the hOGA C-terminal AT domain (hOGA-AT)
.
The structure of
Og
pAT in complex with acetyl coenzyme A (AcCoA) reveals that, by homology modelling, hOGA-AT adopts a variant AT fold with a unique loop creating a deep tunnel. The structures, together with mutagenesis and surface plasmon resonance data, reveal that while the bacterial
Og
pAT binds AcCoA, the hOGA-AT does not, as explained by the lack of key residues normally required to bind AcCoA. Thus, the C-terminal domain of hOGA is a catalytically incompetent ‘pseudo’-AT.
Resistance to ceftazidime in Escherichia coli associated with AcrR, MarR and PBP3 mutations and overexpression of sdiA
Authors: Tavío María M. , Aquili Virginia D. , Vila Jordi , Poveda José B.
Published: October 2013

The mechanisms responsible for the increase in ceftazidime MIC in two Escherichia coli in vitro selected mutants, Caz/20-1 and Caz/20-2, were studied. OmpF loss and overexpression of acrB, acrD and acrF that were associated with acrR and marR mutations and sdiA overexpression, together with mutations A233T and I332V in FtSI (PBP3) resulted in ceftazidime resistance in Caz/20-2, multiplying by 128-fold the ceftazidime MIC in the parental clinical isolate PS/20. Absence of detectable β-lactamase hydrolytic activity in the crude extract of Caz/20-2 was observed, and coincided with Q191K and P209S mutations in AmpC and a nucleotide substitution at −28 in the ampC promoter, whereas β-lactamase hydrolytic activity in crude extracts of PS/20 and Caz/20-1 strains was detected. Nevertheless, a fourfold increase in ceftazidime MIC in Caz/20-1 compared with that in PS/20 was due to the increased transcript level of acrB derived from acrR mutation. The two Caz mutants and PS/20 showed the same mutations in AmpG and ParE.
A strain-specific segment of the RNA-dependent RNA polymerase of grapevine fanleaf virus determines symptoms in Nicotiana species
Authors: Vigne Emmanuelle , Gottula John , Schmitt-Keichinger Corinne , Komar Véronique , Ackerer Léa , Belval Lorène , Rakotomalala Lalaina , Lemaire Olivier , Ritzenthaler Christophe , Fuchs Marc
Published: October 2013

Factors involved in symptom expression of viruses from the genusNepovirusin the familySecoviridaesuch as grapevine fanleaf virus (GFLV) are poorly characterized. To identify symptom determinants encoded by GFLV, infectious cDNA clones of RNA1 and RNA2 of strain GHu were developed and used alongside existing infectious cDNA clones of strain F13 in a reverse genetics approach.In vitrotranscripts of homologous combinations of RNA1 and RNA2 induced systemic infection inNicotiana benthamianaandNicotiana clevelandiiwith identical phenotypes to WT virus strains, i.e. vein clearing and chlorotic spots onN. benthamianaandN. clevelandiifor GHu, respectively, and lack of symptoms on both hosts for F13. The use of assorted transcripts mapped symptom determinants on RNA1 of GFLV strain GHu, in particular within the distal 408 nt of the RNA-dependent RNA polymerase (1EPol), as shown by RNA1 transcripts for which coding regions or fragments derived thereof were swapped. Semi-quantitative analyses indicated no significant differences in virus titre between symptomatic and asymptomatic plants infected with various recombinants. Also, unlike the nepovirus tomato ringspot virus, no apparent proteolytic cleavage of GFLV protein 1EPolwas detected upon virus infection or transient expression inN. benthamiana. In addition, GFLV protein 1EPolfailed to suppress silencing of EGFP in transgenicN. benthamianaexpressing EGFP or to enhance GFP expression in patch assays in WTN. benthamiana. Together, our results suggest the existence of strain-specific functional domains, including a symptom determinant module, on the RNA-dependent RNA polymerase of GFLV.