bluuebunny/crossref_metadata_2025 huggingface dataset:
Early detection of human glioma sphere xenografts in mouse brain using diffusion MRI at 14.1 T
Authors: Porcari P. , Hegi M. E. , Lei H. , Hamou M‐F. , Vassallo I. , Capuani S. , Gruetter R. , Mlynarik V.
Published: September 2016

Glioma models have provided important insights into human brain cancers. Among the investigative tools, MRI has allowed their characterization and diagnosis.

In this study, we investigated whether diffusion MRI might be a useful technique for early detection and characterization of slow‐growing and diffuse infiltrative gliomas, such as the proposed new models, LN‐2669GS and LN‐2540GS glioma sphere xenografts. Tumours grown in these models are not visible in conventional T2‐weighted or contrast‐enhanced T1‐weighted MRI at 14.1 T.

Diffusion‐weighted imaging and diffusion tensor imaging protocols were optimized for contrast by exploring long diffusion times sensitive for probing the microstructural alterations induced in the normal brain by the slow infiltration of glioma sphere cells.

Compared with T2‐weighted images, tumours were properly identified in their early stage of growth using diffusion MRI, and confirmed by localized proton MR spectroscopy as well as immunohistochemistry. The first evidence of tumour presence was revealed for both glioma sphere xenograft models three months after tumour implantation, while no necrosis, oedema or haemorrhage were detected either by MRI or by histology. Moreover, different values of diffusion indices, such as mean diffusivity and fractional anisotropy, were obtained in tumours grown from LN‐2669GS and LN‐2540GS glioma sphere lines. These observations highlighted diverse tumour microstructures for both xenograft models, which were reflected in histology.

This study demonstrates the ability of diffusion MRI techniques to identify and investigate early stages of slow‐growing, invasive tumours in the mouse brain, thus providing a potential imaging biomarker for early detection of tumours in humans.
Aliphatic isocyanurates and polyisocyanurate networks
Authors: Driest P. J. , Lenzi V. , Marques L. S. A. , Ramos M. M. D. , Dijkstra D. J. , Richter F. U. , Stamatialis D. , Grijpma D. W.
Published: September 2016

The production, processing, and application of aliphatic isocyanate (NCO)‐based thermosets such as polyurethane coatings and adhesives are generally limited by the surprisingly high viscosity of tri‐functionality and higher‐functionality isocyanurates. These compounds are essential crosslinking additives for network formation. However, the mechanism by which these high viscosities are caused is not yet understood. In this work, model aliphatic isocyanurates were synthesized and isolated in high purity (>99%), and their viscosities were accurately determined. It was shown that the presence of the NCO group has a strong influence on the viscosity of the system. From density functional theory calculations, a novel and significant bimolecular binding potential of −8.7 kJ/mol was identified between NCO groups and isocyanurate rings, confirming the important role of the NCO group. This NCO‐to‐ring interaction was proposed to be the root cause for the high viscosities observed for NCO‐functional isocyanurate systems. Molecular dynamics simulations carried out to further confirm this influence also suggest that the NCO‐to‐ring interaction causes a significant additional contribution to viscosity. Finally, model functional isocyanurates were further reacted into densely crosslinked polyisocyanurate networks which showed interesting material properties. Copyright © 2016 The Authors Polymers for Advanced Technologies published by John Wiley & Sons, Ltd.
Radical induced cationic frontal polymerization as a versatile tool for epoxy curing and composite production
Authors: Bomze Daniel , Knaack Patrick , Koch Thomas , Jin Huifei , Liska Robert
Published: September 2016

Radical induced cationic frontal polymerization (RICFP) is an extremely powerful and elegant alternative curing technique that allows cationic bulk curing of epoxy resins with very little energy consumption, as well as curing in compartments that are not readily accessible. We recently introduced a bisphenol‐A diglycidylether (BADGE) based system that allows the bubble‐free photocuring of this widely used epoxy resin. In this article, we describe the high storage stability and possibilities to influence the curing speed via the initiator concentrations of different formulations. These properties allow the adjustment of the frontal polymerization to ones need. We also show that the (thermo)mechanical and electrical properties of frontal cured epoxy polymers compares favorably with those of state of the art material. Finally, different strategies to overcome the challenges on producing epoxy resin based mica composites via RICFP are presented. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3751–3759
Conicity of latent tracks in the near surface region as a factor affecting the correct evaluation of track size
Authors: Saifulin Maxim , O'Connell Jacques , Skuratov Vladimir , van Vuuren Arno Janse
Published: September 2016

The difference in track parameters recorded in some oxides at the same energy loss and different ion velocity, the so called “velocity effect”, have been corroborated by various experimental methods. Most of the corresponding data on damage cross section and then on the track radii were found by means of indirect techniques such as Rutherford backscattering spectroscopy in channelling geometry. The contribution of transmission electron microscopy results in the whole data array remains very limited. In this report we present an analysis of existing TEM results related to the “velocity effect” and consider how the conical shape of latent tracks observed in the subsurface region of swift heavy ion irradiated oxides may affect the correct determination of the track size as well as the critical electronic energy loss for track formation. The discussion is based on our cross sectional TEM studies of high energy Bi and Xe ion induced latent tracks in TiO2 and Al2O3 single crystals. To our knowledge there have been no reported cross sectional TEM analyses on Y3Fe5O12, Bi4Ge3O12 and YBa2Cu3O7‐δ in order to verify the cylindrical track assumption. If similar conicity exists in the near surface regions of these materials it may cast some doubt on the validity of the velocity effect. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
New strategies for the synthesis of ZnO and Al‐doped ZnO films by reactive magnetron sputtering at room temperature
Authors: Horwat David , Mickan Martin , Chamorro William
Published: September 2016

We review our recent findings that reactive magnetron sputtering can be operated without thermal assistance to produce epitaxial ZnO films and highly conductive and transparent aluminum‐doped ZnO (AZO) films on large surface area. The growth of epitaxial films requires working in direct current (DC) mode at large oxygen partial pressure but high power impulse magnetron sputtering (HiPIMS) is preferred to optimize the electrical and optical properties of AZO films on large surface areas. The results are interpreted by the ability of DC sputtering to easily oxidize the target surface and the HiPIMS mode cleans and returns it to metallic during pulses. Fast oxygen atoms (ions) may be emitted in large amount using DC and bring fuel to the growing ZnO film to induce epitaxy onto sapphire. The signature of oxygen interstitials is found in DC with increasing magnitude as the oxygen content is increased in the gas phase. In contrast, the discharge voltage plays a significant role in HiPIMS to adjust the sputtering rate and clean the target surface for deposition of slightly sub‐stoichiometric AZO films over the entire range of lateral positions. Thereby, transparent yet highly conductive films with resistivity in the range 4‐15×10‐4 Ωcm can be produced. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Drivers for the deepening of severe European windstorms and their impacts on forecast quality
Authors: Pirret Jennifer S. R. , Knippertz Peter , Trzeciak Tomasz M.
Published: September 2016

European windstorms are a high‐impact weather phenomenon, regularly inflicting substantial damages, both human and economic. This study examines a set of objectively selected intense European windstorms from the 1979–2015 period using re‐analysis and forecast products from the European Centre for Medium‐Range Weather Forecasts (ECMWF). The storms are first categorized with respect to their diabatic relative to baroclinic contribution to deepening using the pressure tendency equation, and secondly with respect to their track relative to the jet stream as the large‐scale element controlling storm deepening and propagation. As expected, baroclinic processes dominate the majority of storms, such that deepening is closely related to warm advection ahead of the cyclone centre. Contributions from diabatic processes vary strongly and exceed those from horizontal temperature advection in 10 out of 58 cases, with values of up to 60%. Remarkably, in several cases, planetary waves in the stratosphere appear to facilitate cyclogenesis but can also act to oppose deepening in a few cases. The diabatic contribution is significantly correlated with the time a given storm spends on the equatorward side of the jet, where there is greater potential for diabatic processes in the warm, moist air. In terms of forecast quality and consistent with previous studies, the storm core pressure is generally underestimated and storms tend to be too slow and shifted south in the forecast, particularly for longer lead times. These biases, however, reduce markedly with the improvement of the operational system over time. There is no systematic dependence of forecast behaviour on the diabatic contribution or track relative to the jet. In the future, some of these analyses should be repeated with homogeneous reforecast data to substantiate these findings better.
Development of Low‐vacuum SIMS instruments with large cluster Ion beam
Authors: Suzuki K. , Kusakari M. , Fujii M. , Seki T. , Aoki T. , Matsuo J.
Published: September 2016

Large cluster ions such as Arn+ (n > 1000) are expected to have a better transmission factor than monomer ions or other small cluster ions because of their large mass, and thus they might be used as a probe in secondary ion mass spectrometry measurements even at low vacuum pressure. In this study, we examined the transmission and sputtering properties of Ar gas cluster ion beam under low vacuum. Current images of a Ni mesh (400 line/inch) obtained with varying target chamber pressure under low vacuum (<50 Pa) indicated that cluster ions could reach the target without wide divergence. Furthermore, it was demonstrated that cluster ions could sputter organic samples even at 80 Pa. Although the sputtering efficiency decreased by two orders of magnitude at 80 Pa, beam focusing (~20 µm) was achieved with a beam current of 4 nA, that is, one or two orders of magnitude higher than the conventional Ar gas cluster ion beam source. From these results, we concluded that low‐vacuum secondary ion mass spectrometry measurements (<80 Pa) might be achievable. Copyright © 2016 John Wiley & Sons, Ltd.
A novel model‐driven approach for seamless integration
Authors: Mustacoglu Ahmet F.
Published: September 2016

This research mentions integration problems and describes a novel model‐driven approach that intend to reach a higher degree of interoperability among different software development tools coming from different technological spaces (TSs) by representing data of tools through the models. The proposed concept introduce a way to integrate various software related tools and aim to provide a modular syntax for tool integration that leverage the collaboration of different tools. In this work, the proposed approach has been tested through a case–study by demonstrating a single aspect of the model‐driven tool integration because the model‐driven tool integration has a wide scope and it is difficult to show all aspects of it in one research. It is proved that the model‐driven tool integration is possible based on the proposed concept between different TSs, and the formulation of the proposed approach is provided. As the results indicate, the proposed system integrates selected software‐related tools coming from different TSs and enables them to use each other's capabilities. This work paves the way to contribute for the standardization efforts of the model‐driven tool integration. Finally, further research opportunities are provided. Copyright © 2016 John Wiley & Sons, Ltd.
Psychometric Properties of the Persian Version of Spiritual Well-Being Scale in Patients with Acute Myocardial Infarction
Authors: Soleimani Mohammad Ali , Pahlevan Sharif Saeed , Allen Kelly A. , Yaghoobzadeh Ameneh , Sharif Nia Hamid , Gorgulu Ozkan
Published: September 2016

The purpose of this study was to assess the psychometric properties of the Persian version of Spiritual Well-Being Scale (SWBS) in patients with acute myocardial infarction. A multisite, cross-sectional survey was employed to determine the instrument’s reliability (Cronbach’s α and construct reliability) and validity (face, content, and construct). Using systematic sampling of adult outpatients at primary care clinic sites in the Qazvin City, Iran (N = 300), it was found that the Cronbach’s alpha and construct reliability of both factors associated with the SWBS were above 0.7. The construct validity of the scale was determined using exploratory factor analysis. The findings supported two factors: relation with God and relation with life. Further investigation through confirmatory factor analysis (eigenvalues of greater than one) confirmed a third factor construct associated with the SWBS. A total of 50.65 % of the variance were explained by these three factors. The overall findings of the study demonstrated that the SWBS is a valid and reliable instrument that has potential utility in future research and clinical practice settings.
Using reflection to influence practice: student perceptions of daily reflection in clinical education
Authors: Larsen Douglas P. , London Daniel A. , Emke Amanda R.
Published: September 2016

Purpose Reflection is a key element in learning from experience, but the impact of most programmes of reflection on daily practice remains unclear. We investigated students’ perceptions of adding a daily written reflection assignment to a clinical rotation.
Methods Third-year medical students on a single two-week rotation completed daily reflections analyzing their performance. Programme evaluation used a 33-question anonymized survey. Quantitative data were summarized and qualitative responses coded for recurring themes.
Results Twenty-six students completed the survey (90 % response rate). Eighty-five percent of students felt that the daily reflections had a positive impact on their learning from clinical experience. Seventy-seven percent of students reported that the programme changed their awareness of their thoughts and actions, and 80 % felt that it improved their recall of experiences. A greater sense of mindfulness and focus on self-improvement were major themes that emerge from students’ descriptions of the role of daily reflections in their learning.
Conclusion Overall, daily reflections demonstrated a positive learning influence. This exploratory study suggests students may benefit from more frequent, short reflections as opposed to more typically spaced reflective assignments.
What parents don't know: Disclosure and secrecy in a sample of urban adolescents
Authors: Jäggi Lena , Drazdowski Tess K. , Kliewer Wendy
Published: September 2016

Research with two‐parent European households has suggested that secrecy, and not disclosure of information per se, predicts adolescent adjustment difficulties. The present study attempted to replicate this finding using data from a 4‐wave study of 358 poor, urban adolescents (47% male; M age = 12 yrs) in the United States, most of whom (>92%) were African American. Adolescents self‐reported secrecy, disclosure, depressive symptoms, and delinquency at each wave. Confirmatory factor analyses revealed that a two‐factor model with secrecy and disclosure as separate, but correlated, factors was a better fit than a one‐factor model. However, predictive models differed from previous research. Secrecy did not predict depressive symptoms, rather depressive symptoms predicted secrecy. For delinquency, there were significant paths from both secrecy to delinquency and delinquency to secrecy, as well as from delinquency to disclosure. These results did not differ by age or sex. Comparisons with previous findings are discussed.
Comparison of the Calabi and Mabuchi geometries and applications to geometric flows
Authors: Darvas Tamás
Published: September 2016

Suppose

(X,\omega )

is a compact Kähler manifold. We introduce and explore the metric geometry of the

L^{p,q}

-Calabi Finsler structure on the space of Kähler metrics

\mathcal{H}

. After noticing that the

L^{p,q}

-Calabi and

L^{p^{′}}

-Mabuchi path length topologies on

\mathcal{H}

do not typically dominate each other, we focus on the finite entropy space

\mathcal{E}^{\mathrm{Ent}}

, contained in the intersection of the

L^{p}

-Calabi and

L^{1}

-Mabuchi completions of

\mathcal{H}

and find that after a natural strengthening, the

L^{p}

-Calabi and

L^{1}

-Mabuchi topologies coincide on

\mathcal{E}^{\mathrm{Ent}}

. As applications to our results, we give new convergence results for the Kähler–Ricci flow and the weak Calabi flow.
Ultrasound‐Guided Fasciotomy for Chronic Exertional Compartment Syndrome: A Cadaveric Investigation
Authors: Lueders Daniel R. , Sellon Jacob L. , Smith Jay , Finnoff Jonathan T.
Published: September 2016

Background

Chronic exertional compartment syndrome (CECS) is a common cause of exertional leg pain. It is commonly treated with a surgical fasciotomy, which has a surgical complication rate of up to 16% and takes approximately 6‐12 weeks to return to preprocedure activity levels. Therefore, the development of a less invasive, effective outpatient intervention to treat CECS is desirable.

Objective

To describe and validate an ultrasound‐guided (USG) fasciotomy technique for the anterior and lateral compartments of the lower limb in an unembalmed cadaveric model.

Design

Prospective, cadaveric laboratory investigation.

Setting

Academic institution procedural skills laboratory.

Subjects

Ten unembalmed cadaveric knee‐ankle‐foot specimens from 1 female (2 specimens) and 7 male donors aged 62‐91 years (mean 78.6 years) with body mass indices of 18.9‐35.3 kg/m2 (mean 27.1 kg/m2).

Methods

Two experienced operators each performed USG anterior and lateral compartment fasciotomies on 5 unembalmed cadaveric legs. A third physician subsequently dissected the legs to assess the continuity of the fasciotomies and to identify any neurovascular damage related to the procedures.

Main Outcome Measures

Fasciotomy length (in centimeters) and classification by completeness (achieved target length or did not achieve target length) and continuity (continuous or discontinuous) based on predetermined criteria. Muscles, retinaculae, and neurovascular structures were assessed for damage.

Results

No neurovascular injuries occurred in any of the 20 USG fasciotomies. The average fasciotomy length was 22.5 cm. All 20 of the fasciotomies achieved the target length. A continuous cephalocaudal fasciotomy was accomplished in 13 of 20 fasciotomies. When a fasciotomy was not continuous, the average length and number of intact fascial bands was 1.52 cm and 2.3, respectively.

Conclusions

USG fasciotomy of the anterior and lateral leg compartments can be safely performed in a cadaveric model and can achieve a fasciotomy length comparable to surgical fasciotomy. Most procedures successfully achieved a continuous cephalocaudal fasciotomy, although small areas of intact fascial bands were identified in approximately one‐third of procedures. The clinical significance of this finding is indeterminate. Given the safety demonstrated with this minimally invasive USG fasciotomy in a cadaveric model, further research is warranted to develop and refine the technique for clinical application.

Level of Evidence

Not applicable.
The seventeenth-century English and Scottish reception of Francis de Sales’An Introduction to a Devout Life
Authors: Hardy Mary
Published: September 2016

St Francis de Sales’ devotional manual,An Introduction to a Devout Life(1609), had a complex but fascinating reception history in seventeenth-century England and Scotland. Collectively, the English-language editions in this century include two translations and, perhaps most interestingly, several reformed editions. It is curious that a post-Reformation, Tridentine Catholic work, written by a French bishop dedicated to converting Protestant ‘Heretiques,’ would appeal to both Catholics and Protestants alike. Most of the seventeenth-century English editions were published abroad in Douai, Paris, St Omer, and Rouen, places that were home to many English and Scottish exiled communities, both lay and religious. Two of the three reformed editions were published in England, evidence of theIntroduction’s widespread readership and its importance to seventeenth-century English devotion. Finally, during James II’s reign two Catholic editions were openly published, one in England and the other in Scotland.
Chemical investigations of volatile kairomones produced by Hyphantria cunea (Drury), a host of the parasitoid Chouioia cunea Yang
Authors: Zhu G. , Pan L. , Zhao Y. , Zhang X. , Wang F. , Yu Y. , Fan W. , Liu Q. , Zhang S. , Li M.
Published: September 2016

In tritrophic ‘plants–herbivores–natural enemies’ systems, there are relatively few reports concerning the role(s) of kairomones in pupal parasitism. Chouioia cunea Yang (Hymenoptera: Eulophidae), an endoparasitic chalcid wasp, parasitizes pupae of the fall webworm (Hyphantria cunea Drury). The role of host-related kairomones was investigated using electroantennogram (EAG) and behavioral techniques. Chemicals from some host stages (pupae) and host by-products (frass), induced arrestment behavior of female parasitoids, while chemicals from prepupae, were inactive. Gas chromatography–mass spectrometry analysis of volatiles collected from pupae, frass and prepupae using solid-phase microextration revealed seven compounds with carbon chain lengths ranging from C4 to C20. All of the chemicals elicited significant EAG responses in C. cunea. Y-tube olfactometer bioassays demonstrated a significant positive response of mated female C. cunea to 1-dodecene. These data provide a better understanding of the host location mechanisms of pupal parasitoid.
A Deheroization of a Hero of National Freedom. A Case Study of Competing Regimes of Memory
Authors: Dénes Iván Zoltán
Published: September 2016

This case study concerns the analysis of a symbolic national grievance: the interpretation of a one-sided, unempathetic deheroization of a champion of national liberty, its historiographical and memory political contexts, and its outcome, strengthening the dichotomous conflicting systems of memory.
European Inflation and the Spanish Stock Market
Authors: Jareño Francisco , Navarro Eliseo
Published: September 2016

This study examines the short-run response of daily stock prices in the Spanish market to the announcements of inflation news at a sector level at the moments when the Spanish authorities announced the IPC (consumer price index) during the period 1995–2004. The study also incorporates two novel explanatory variables: core inflation and ‘non-core’ inflation rate components on the one hand, and the spread between the Spanish and European inflation rates (harmonized) on the other hand. It is concluded that the ‘non-core’ component of the inflation rate, which is more volatile, has negative effects on some sector returns; additionally, in drawing too far apart from the European inflation rate, the Spanish inflation rate negatively affects sector returns, such as in the ‘Consumer Goods’ sector, which is subject to strong foreign competition. In the long-term analysis, the lagged core inflation (structural component) negatively affects sector returns.
Home-based anthropometric, blood pressure and pulse measurements in young children by trained data collectors in the National Children’s Study
Authors: Zimowski Michele , Moye Jack , Dugoni Bernard , Heim Viox Melissa , Cohen Hildie , Winfrey Krishna
Published: September 2016

Objective

The current study assessed whether home-based data collection by trained data collectors can produce high-quality physical measurement data in young children.

Design

The study assessed the quality of intra-examiner measurements of blood pressure, pulse rate and anthropometric dimensions using intra-examiner reliability and intra-examiner technical error of measurement (TEM).

Setting

Non-clinical, primarily private homes of National Children’s Study participants in twenty-two study locations across the USA.

Subjects

Children in four age groups: 5–7 months (n 91), 11–16 months (n 393), 23–28 months (n 1410) and 35–40 months (n 800).

Results

Absolute TEM ranged in value from 0·09 to 16·21, varying widely by age group and measure, as expected. Relative TEM spanned from 0·27 to 13·71 across age groups and physical measures. Reliabilities for anthropometric measurements by age group and measure ranged from 0·46 to >0·99 with most exceeding 0·90, suggesting that the large majority of anthropometric measures can be collected in a home-based setting on young children by trained data collectors. Reliabilities for blood pressure and pulse rate measurements by age group ranged from 0·21 to 0·74, implying these are less reliably measured with young children when taken in the data collection context described here.

Conclusions

Reliability estimates >0·95 for weight, length, height, and thigh, waist and head circumference, and >0·90 for triceps and subscapular skinfolds, indicate that these measures can be collected in the field by trained data collectors without compromising data quality. These estimates can be used for interim evaluations of data collector training and measurement protocols.
Gluten contamination in gluten-free bakery products: a risk for coeliac disease patients
Authors: Farage Priscila , de Medeiros Nóbrega Yanna Karla , Pratesi Riccardo , Gandolfi Lenora , Assunção Pedro , Zandonadi Renata Puppin
Published: September 2016

Objective

The present study aimed to assess the safety of gluten-free bakery products for consumption by coeliac patients.

Design/setting

In the current exploratory cross-sectional quantitative study, a total of 130 samples were collected from twenty-five bakeries in Brasilia (Brazil). For the quantification of gluten, an ELISA was used. The threshold of 20 ppm gluten was considered as the safe upper limit for gluten-free food, as proposed in the Codex Alimentarius.

Results

The results revealed a total of 21·5 % of contamination among the bakery products sampled. Sixty-four per cent of the bakeries sold at least one contaminated product in our sample.

Conclusions

These findings represent a risk for coeliac patients since the ingestion of gluten traces may be sufficient to adversely impact on their health.
Positivity and Negativity in Interparental Conflict
Authors: Zemp Martina , Bodenmann Guy , Backes Sabine , Sutter-Stickel Dorothee , Bradbury Thomas N.
Published: September 2016

Abstract. Although children are known to be highly sensitive to interparental conflict, important questions remain regarding which specific combinations of positive and negative behaviors as well as verbal and nonverbal expressions are most predictive of children’s perceptions. In this pilot study, we examined observational data on interparental conflict as predictors of children’s reports of perceived threat and insecurity in 43 families. Fathers’ nonverbal negativity was strongly linked to children’s perceived threat and insecure family representations, but both parents’ nonverbal and mothers’ verbal positivity buffered its impact on children. Our findings support previous research findings that parents’ negativity may have less adverse effects on children when it takes place in a positive family climate.
A second DNA binding site in human BRCA2 promotes homologous recombination
Authors: von Nicolai Catharina , Ehlén Åsa , Martin Charlotte , Zhang Xiaodong , Carreira Aura
Published: September 2016

BRCA2 tumour-suppressor protein is well known for its role in DNA repair by homologous recombination (HR); assisting the loading of RAD51 recombinase at DNA double-strand breaks. This function is executed by the C-terminal DNA binding domain (CTD) which binds single-stranded (ss)DNA, and the BRC repeats, which bind RAD51 and modulate its assembly onto ssDNA. Paradoxically, analysis of cells resistant to DNA damaging agents missing the CTD restore HR proficiency, suggesting another domain may take over its function. Here, we identify a region in the N terminus of BRCA2 that exhibits DNA binding activity (NTD) and provide evidence for NTD promoting RAD51-mediated HR. A missense variant detected in breast cancer patients located in the NTD impairs HR stimulation on dsDNA/ssDNA junction containing substrates. These findings shed light on the function of the N terminus of BRCA2 and have implications for the evaluation of breast cancer variants.
Metastatic progression is associated with dynamic changes in the local microenvironment
Authors: Aiello Nicole M. , Bajor David L. , Norgard Robert J. , Sahmoud Amine , Bhagwat Neha , Pham Minh N. , Cornish Toby C. , Iacobuzio-Donahue Christine A. , Vonderheide Robert H. , Stanger Ben Z.
Published: September 2016

Most cancer-associated deaths result from metastasis. However, it remains unknown whether the size, microenvironment or other features of a metastatic lesion dictate its behaviour or determine the efficacy of chemotherapy in the adjuvant (micrometastatic) setting. Here we delineate the natural history of metastasis in an autochthonous model of pancreatic ductal adenocarcinoma (PDAC), using lineage tracing to examine the evolution of disseminated cancer cells and their associated microenvironment. With increasing size, lesions shift from mesenchymal to epithelial histology, become hypovascular and accumulate a desmoplastic stroma, ultimately recapitulating the primary tumours from which they arose. Moreover, treatment with gemcitabine and nab-paclitaxel significantly reduces the overall number of metastases by inducing cell death in lesions of all sizes, challenging the paradigm that PDAC stroma imposes a critical barrier to drug delivery. These results illuminate the cellular dynamics of metastatic progression and suggest that adjuvant chemotherapy affords a survival benefit by directly targeting micrometastases.
Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS
Authors: Miyake Takahito , Nakamura Saki , Zhao Meng , So Kanako , Inoue Keisuke , Numata Tomohiro , Takahashi Nobuaki , Shirakawa Hisashi , Mori Yasuo , Nakagawa Takayuki , Kaneko Shuji
Published: September 2016

Mammalian transient receptor potential ankyrin 1 (TRPA1) is a polymodal nociceptor that plays an important role in pain generation, but its role as a cold nociceptor is still controversial. Here, we propose that TRPA1 can sense noxious cold via transduction of reactive oxygen species (ROS) signalling. We show that inhibiting hydroxylation of a proline residue within the N-terminal ankyrin repeat of human TRPA1 by mutation or using a prolyl hydroxylase (PHD) inhibitor potentiates the cold sensitivity of TRPA1 in the presence of hydrogen peroxide. Inhibiting PHD in mice triggers mouse TRPA1 sensitization sufficiently to sense cold-evoked ROS, which causes cold hypersensitivity. Furthermore, this phenomenon underlies the acute cold hypersensitivity induced by the chemotherapeutic agent oxaliplatin or its metabolite oxalate. Thus, our findings provide evidence that blocking prolyl hydroxylation reveals TRPA1 sensitization to ROS, which enables TRPA1 to convert ROS signalling into cold sensitivity.
Managing multimorbidity in primary care in patients with chronic respiratory conditions
Authors: Morrison Deborah , Agur Karolina , Mercer Stewart , Eiras Andreia , González-Montalvo Juan I , Gruffydd-Jones Kevin
Published: September 2016

The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions. Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs. Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety. Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease. This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age. The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy. The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions. The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy. Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams.
Primates’ behavioural responses to tourists: evidence for a trade-off between potential risks and benefits
Authors: Maréchal Laëtitia , MacLarnon Ann , Majolo Bonaventura , Semple Stuart
Published: September 2016

The presence of, and interactions with tourists can be both risky and beneficial for wild animals. In wildlife tourism settings, animals often experience elevated rates of aggression from conspecifics, and they may also be threatened or physically aggressed by the tourists themselves. However, tourist provisioning of wild animals provides them with highly desirable foods. In situations of conflicting motivations such as this, animals would be expected to respond using behavioural coping mechanisms. In the present study, we investigated how animals respond to tourist pressure, using wild adult Barbary macaques in the Middle Atlas Mountains, Morocco, as a case study. We found evidence that these animals use a range of different behavioural coping mechanisms–physical avoidance, social support, affiliative, aggressive and displacement behaviours–to cope with the stress associated with tourists. The pattern of use of such behaviours appears to depend on a trade-off between perceived risks and potential benefits. We propose a framework to describe how animals respond to conflicting motivational situations, such as the presence of tourists, that present simultaneously risks and benefits.
Amyloid structure exhibits polymorphism on multiple length scales in human brain tissue
Authors: Liu Jiliang , Costantino Isabel , Venugopalan Nagarajan , Fischetti Robert F. , Hyman Bradley T. , Frosch Matthew P. , Gomez-Isla Teresa , Makowski Lee
Published: September 2016

Aggregation of Aβ amyloid fibrils into plaques in the brain is a universal hallmark of Alzheimer’s Disease (AD), but whether plaques in different individuals are equivalent is unknown. One possibility is that amyloid fibrils exhibit different structures and different structures may contribute differentially to disease, either within an individual brain or between individuals. However, the occurrence and distribution of structural polymorphisms of amyloid in human brain is poorly documented. Here we use X-ray microdiffraction of histological sections of human tissue to map the abundance, orientation and structural heterogeneities of amyloid. Our observations indicate that (i) tissue derived from subjects with different clinical histories may contain different ensembles of fibrillar structures; (ii) plaques harboring distinct amyloid structures can coexist within a single tissue section and (iii) within individual plaques there is a gradient of fibrillar structure from core to margins. These observations have immediate implications for existing theories on the inception and progression of AD.
Catalytic Thr or Ser Residue Modulates Structural Switches in 2-Cys Peroxiredoxin by Distinct Mechanisms
Authors: Tairum Carlos A. , Santos Melina Cardoso , Breyer Carlos A. , Geyer R. Ryan , Nieves Cecilia J. , Portillo-Ledesma Stephanie , Ferrer-Sueta Gerardo , Toledo José Carlos , Toyama Marcos H. , Augusto Ohara , Netto Luis E. S. , de Oliveira Marcos A.
Published: September 2016

Typical 2-Cys Peroxiredoxins (2-Cys Prxs) reduce hydroperoxides with extraordinary rates due to an active site composed of a catalytic triad, containing a peroxidatic cysteine (CP), an Arg, and a Thr (or Ser). 2-Cys Prx are involved in processes such as cancer; neurodegeneration and host-pathogen interactions. During catalysis, 2-Cys Prxs switch between decamers and dimers. Analysis of 2-Cys Prx structures in the fully folded (but not locally unfolded) form revealed a highly conserved, non-conventional hydrogen bond (CH-π) between the catalytic triad Thr of a dimer with an aromatic residue of an adjacent dimer. In contrast, structures of 2-Cys Prxs with a Ser in place of the Thr do not display this CH-π bond. Chromatographic and structural data indicate that the Thr (but not Ser) destabilizes the decamer structure in the oxidized state probably through steric hindrance. As a general trend, mutations in a yeast 2-Cys Prx (Tsa1) favoring the dimeric state also displayed a decreased catalytic activity. Remarkably, yeast naturally contains Thr-Ser variants (Tsa1 and Tsa2, respectively) with distinct oligomeric stabilities in their disulfide states.
Superconductor to Mott insulator transition in YBa2Cu3O7/LaCaMnO3 heterostructures
Authors: Gray B. A. , Middey S. , Conti G. , Gray A. X. , Kuo C.-T. , Kaiser A. M. , Ueda S. , Kobayashi K. , Meyers D. , Kareev M. , Tung I. C. , Liu Jian , Fadley C. S. , Chakhalian J. , Freeland J. W.
Published: September 2016

The superconductor-to-insulator transition (SIT) induced by means such as external magnetic fields, disorder or spatial confinement is a vivid illustration of a quantum phase transition dramatically affecting the superconducting order parameter. In pursuit of a new realization of the SIT by interfacial charge transfer, we developed extremely thin superlattices composed of high Tc superconductor YBa2Cu3O7 (YBCO) and colossal magnetoresistance ferromagnet La0.67Ca0.33MnO3 (LCMO). By using linearly polarized resonant X-ray absorption spectroscopy and magnetic circular dichroism, combined with hard X-ray photoelectron spectroscopy, we derived a complete picture of the interfacial carrier doping in cuprate and manganite atomic layers, leading to the transition from superconducting to an unusual Mott insulating state emerging with the increase of LCMO layer thickness. In addition, contrary to the common perception that only transition metal ions may respond to the charge transfer process, we found that charge is also actively compensated by rare-earth and alkaline-earth metal ions of the interface. Such deterministic control of Tc by pure electronic doping without any hindering effects of chemical substitution is another promising route to disentangle the role of disorder on the pseudo-gap and charge density wave phases of underdoped cuprates.
Extension of the classical classification of β-turns
Authors: de Brevern Alexandre G.
Published: September 2016

The functional properties of a protein primarily depend on its three-dimensional (3D) structure. These properties have classically been assigned, visualized and analysed on the basis of protein secondary structures. The β-turn is the third most important secondary structure after helices and β-strands. β-turns have been classified according to the values of the dihedral angles φ and ψ of the central residue. Conventionally, eight different types of β-turns have been defined, whereas those that cannot be defined are classified as type IV β-turns. This classification remains the most widely used. Nonetheless, the miscellaneous type IV β-turns represent 1/3rdof β-turn residues. An unsupervised specific clustering approach was designed to search for recurrent new turns in the type IV category. The classical rules of β-turn type assignment were central to the approach. The four most frequently occurring clusters defined the new β-turn types. Unexpectedly, these types, designated IV1, IV2, IV3and IV4, represent half of the type IV β-turns and occur more frequently than many of the previously established types. These types show convincing particularities, in terms of both structures and sequences that allow for the classical β-turn classification to be extended for the first time in 25 years.
The Tetraodon nigroviridis reference transcriptome: developmental transition, length retention and microsynteny of long non-coding RNAs in a compact vertebrate genome
Authors: Basu Swaraj , Hadzhiev Yavor , Petrosino Giuseppe , Nepal Chirag , Gehrig Jochen , Armant Olivier , Ferg Marco , Strahle Uwe , Sanges Remo , Müller Ferenc
Published: September 2016

Pufferfish such as fugu and tetraodon carry the smallest genomes among all vertebrates and are ideal for studying genome evolution. However, comparative genomics using these species is hindered by the poor annotation of their genomes. We performed RNA sequencing during key stages of maternal to zygotic transition of Tetraodon nigroviridis and report its first developmental transcriptome. We assembled 61,033 transcripts (23,837 loci) representing 80% of the annotated gene models and 3816 novel coding transcripts from 2667 loci. We demonstrate the similarities of gene expression profiles between pufferfish and zebrafish during maternal to zygotic transition and annotated 1120 long non-coding RNAs (lncRNAs) many of which differentially expressed during development. The promoters for 60% of the assembled transcripts result validated by CAGE-seq. Despite the extreme compaction of the tetraodon genome and the dramatic loss of transposons, the length of lncRNA exons remain comparable to that of other vertebrates and a small set of lncRNAs appears enriched for transposable elements suggesting a selective pressure acting on lncRNAs length and composition. Finally, a set of lncRNAs are microsyntenic between teleost and vertebrates, which indicates potential regulatory interactions between lncRNAs and their flanking coding genes. Our work provides a fundamental molecular resource for vertebrate comparative genomics and embryogenesis studies.
High steady-state column density of I(2P3/2) atoms from I2 photodissociation at 532 nm: Towards parity non-conservation measurements
Authors: Katsoprinakis G. E. , Chatzidrosos G. , Kypriotakis J. A. , Stratakis E. , Rakitzis T. P.
Published: September 2016

Steady-state column densities of 1017 cm−2 of I(2P3/2) atoms are produced from photodissociation of I2 vapour at 290.5 K using 5 W of 532 nm laser light. Recombination of the I(2P3/2) atoms at the cell walls is minimized by coating the cell surface with a hydrophobic silane (dimethyldichlorosilane/DMDCS). Operation at room temperature, and at an I2 vapour pressure of ~0.2 mbar, without using a buffer gas, allows relatively low Lorentz and Doppler widths of ~2π × 1.5 (FWHM) and ~2π × 150 (HW at 1/e2) Mrad/s, respectively, at the "Equation missing" M1 transition of atomic iodine at 1315 nm. These high column densities and low linewidths are favorable for parity nonconservation optical rotation measurements near this M1 transition. Furthermore, as the cell is completely sealed, this method of production of high-density 127I(2P3/2) atoms is also compatible with using iodine radioisotopes, such as for the production of high-density 129I(2P3/2).
α-Synuclein is a Novel Microtubule Dynamase
Authors: Cartelli Daniele , Aliverti Alessandro , Barbiroli Alberto , Santambrogio Carlo , Ragg Enzio M. , Casagrande Francesca V.M. , Cantele Francesca , Beltramone Silvia , Marangon Jacopo , De Gregorio Carmelita , Pandini Vittorio , Emanuele Marco , Chieregatti Evelina , Pieraccini Stefano , Holmqvist Staffan , Bubacco Luigi , Roybon Laurent , Pezzoli Gianni , Grandori Rita , Arnal Isabelle , Cappelletti Graziella
Published: September 2016

α-Synuclein is a presynaptic protein associated to Parkinson’s disease, which is unstructured when free in the cytoplasm and adopts α helical conformation when bound to vesicles. After decades of intense studies, α-Synuclein physiology is still difficult to clear up due to its interaction with multiple partners and its involvement in apletoraof neuronal functions. Here, we looked at the remarkably neglected interplay between α-Synuclein and microtubules, which potentially impacts on synaptic functionality. In order to identify the mechanisms underlying these actions, we investigated the interaction between purified α-Synuclein and tubulin. We demonstrated that α-Synuclein binds to microtubules and tubulin α2β2tetramer; the latter interaction inducing the formation of helical segment(s) in the α-Synuclein polypeptide. This structural change seems to enable α-Synuclein to promote microtubule nucleation and to enhance microtubule growth rate and catastrophe frequency, bothin vitroandin cell. We also showed that Parkinson’s disease-linked α-Synuclein variants do not undergo tubulin-induced folding and cause tubulin aggregation rather than polymerization. Our data enable us to propose α-Synuclein as a novel, foldable, microtubule-dynamase, which influences microtubule organisation through its binding to tubulin and its regulating effects on microtubule nucleation and dynamics.
Global analysis of differential gene expression related to long-term sperm storage in oviduct of Chinese Soft-Shelled Turtle Pelodiscus sinensis
Authors: Liu Tengfei , Yang Ping , Chen Hong , Huang Yufei , Liu Yi , Waqas Yasir , Ahmed Nisar , Chu Xiaoya , Chen Qiusheng
Published: September 2016

Important evolutionary and ecological consequences arise from the ability of female turtles to store viable spermatozoa for an extended period. Although previous morphological studies have observed the localization of spermatozoa inPelodiscus sinensisoviduct, no systematic study on the identification of genes that are involved in long-term sperm storage has been performed. In this study, the oviduct ofP. sinensisat different phases (reproductive and hibernation seasons) was prepared for RNA-Seq and gene expression profiling. In total, 2,662 differentially expressed genes (DEGs) including 1,224 up- and 1,438 down-regulated genes were identified from two cDNA libraries. Functional enrichment analysis indicated that many genes were predominantly involved in the immune response, apoptosis pathway and regulation of autophagy. RT-qPCR, ELISA, western blot and IHC analyses showed that the expression profiles of mRNA and protein in selected DEGs were in consistent with results from RNA-Seq analysis. Remarkably, TUNEL analysis revealed the reduced number of apoptotic cells during sperm storage. IHC and TEM analyses found that autophagy occurred in the oviduct epithelial cells, where the spermatozoa were closely attached. The outcomes of this study provide fundamental insights into the complex sperm storage regulatory process and facilitate elucidating the mechanism of sperm storage inP. sinensis.