bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers
Authors: Katchman Benjamin A. , Barderas Rodrigo , Alam Rizwan , Chowell Diego , Field Matthew S. , Esserman Laura J. , Wallstrom Garrick , LaBaer Joshua , Cramer Daniel W. , Hollingsworth Michael A. , Anderson Karen S.
Published: April 2016

Purpose

Mutations in TP53 induce autoantibody immune responses in a subset of cancer patients, which have been proposed as biomarkers for early detection. Here, we investigate the association of p53‐specific autoantibodies with multiple tumor subtypes and determine the association with p53 mutation status and epitope specificity.

Experimental design

IgG p53 autoantibodies (p53‐AAb), were quantified in 412 serum samples using a programmable ELISA assay from patients with serous ovarian, pancreatic adenocarcinoma, and breast cancer. To determine if patients generated mutation‐specific autoantibodies we designed a panel of the most relevant 51 p53 point mutant proteins, to be displayed on custom programmable protein microarrays. To determine the epitope specificity we displayed 12 overlapping tiling fragments and 38 N‐ and C‐terminal deletions spanning the length of the wild‐type p53 protein.

Results

We detected p53‐AAb with sensitivities of 58.8% (ovarian), 22% (pancreatic), 32% (triple negative breast cancer), and 10.2% (HER2+ breast cancer) at 94% specificity. Sera with p53‐AAb contained broadly reactive autoantibodies to 51 displayed p53 mutant proteins, demonstrating a polyclonal response to common epitopes. All p53‐AAb displayed broad polyclonal immune response to both continuous and discontinuous epitopes at the N‐ and C‐terminus as well as the DNA‐binding domain.

Conclusion and clinical relevance

In this comprehensive analysis, mutations in tumor p53 induce strong, polyclonal autoantibodies with broadly reactive epitope specificity.
Linking Subcellular Disturbance to Physiological Behavior and Toxicity Induced by Quantum Dots in Caenorhabditis elegans
Authors: Wang Qin , Zhou Yanfeng , Song Bin , Zhong Yiling , Wu Sicong , Cui Rongrong , Cong Haixia , Su Yuanyuan , Zhang Huimin , He Yao
Published: April 2016

The wide‐ranging applications of fluorescent semiconductor quantum dots (QDs) have triggered increasing concerns about their biosafety. Most QD‐related toxicity studies focus on the subcellular processes in cultured cells or global physiological effects on whole animals. However, it is unclear how QDs affect subcellular processes in living organisms, or how the subcellular disturbance contributes to the overall toxicity. Here the behavior and toxicity of QDs of three different sizes in Caenorhabditis elegans (C. elegans) are systematically investigated at both the systemic and the subcellular level. Specifically, clear size‐dependent distribution and toxicity of the QDs in the digestive tract are observed. Short‐term exposure of QDs leads to acute toxicity on C. elegans, yet incurring no lasting, irreversible damage. In contrast, chronic exposure of QDs severely inhibits development and shortens lifespan. Subcellular analysis reveals that endocytosis and nutrition storage are disrupted by QDs, which likely accounts for the severe deterioration in growth and longevity. This work reveals that QDs invasion disrupts key subcellular processes in living organisms, and may cause permanent damage to the tissues and organs over long‐term retention. The findings provide invaluable information for safety evaluations of QD‐based applications and offer new opportunities for design of novel nontoxic nanoprobes.
Role of Aif1 in regulation of cell death under environmental stress in Candida albicans
Authors: Ma Feiyang , Zhang Yueqi , Wang Yuzhou , Wan Yajuan , Miao Yunheng , Ma Tianyu , Yu Qilin , Li Mingchun
Published: April 2016

Apoptosis‐inducing factor (AIF) is a conserved flavoprotein localized in the mitochondria, inducing apoptosis after translocation into the nucleus. However, its role in the important fungal pathogen, Candida albicans, remains to be investigated. In this study, we find that the C. albicans AIF protein Aif1, similar to its homologues in other organisms, is localized at the mitochondria and translocated into the nucleus under apoptosis‐inducing conditions. Moreover, deletion of AIF1 causes attenuated apoptosis in this pathogen under apoptosis‐inducing conditions, such as the treatment of 2 mm H2O2, 10 mm acetic acid or 0.08 mg/l caspofungin, and its overexpression enhances this process. Interestingly, treatment with high levels of these agents leads to reversed sensitivity of aif1Δ/Δ and the overexpression strain AIF1ov. In addition, the virulence of C. albicans is not affected by deletion or overexpression of AIF1. Hence, C. albicans Aif1, as a mitochondria‐localized protein, plays a dual role in the regulation of cell death under different concentrations of the stress‐caused agents. Copyright © 2016 John Wiley & Sons, Ltd.
Current advances and prospectus of viral resistance in horticultural crops
Authors: Yeam Inhwa
Published: April 2016

Viruses are a major threat causing massive yield loss and economical damage to crop production worldwide. Through complex evolutionary processes, plants encounter and overcome viral infection by developing effective resistance mechanisms. Over the past decade, remarkable progress has been made in understanding the nature of plant resistance to viruses at the molecular level. This review summarizes the major resistance strategies that plants use to prevent viral infection. Recent investigations suggest that antiviral RNA silencing is the most prevalent defense strategy in plants. Other forms of resistance include R gene-mediated resistance and host factor-related recessive resistance. Naturally occurring resistances arise and are maintained in numerous virus-plant pathosystems based mainly on arms-race relationships and the cost-efficiency of resistance acquisition. In addition to the current status of the known resistance mechanisms, this review discusses the future prospectus for the practical application of plant resistances that influence resistance durability in agricultural ecosystems. Such applications include molecular breeding strategies using advanced molecular marker systems and the utilization of trans- or cis- genetics via the acquisition of engineered disease resistances.
Clinical Issues‐May 2016
Authors: Van Wicklin Sharon A.
Published: April 2016

This Month

Variations in documenting surgical wound classification

Key words: surgical wound classification, clean, clean‐contaminated, contaminated, dirty.

Wearing long‐sleeved jackets while preparing and packaging items for sterilization

Key words: long‐sleeved jackets, organic material, sterile processing.

Endoscopic transmission of prions

Key words: prions, high‐risk tissue, low‐risk tissue, Creutzfeldt‐Jakob disease (CJD), variant Creutzfeldt‐Jakob disease (vCJD).

Wearing gloves when handling flexible endoscopes

Key words: gloves, low‐protein, powder‐free, natural rubber latex gloves, latex‐free gloves.
Turbulent patterns made simple?
Authors: Manneville P.
Published: April 2016

An observed, spectacular and puzzling distinctive feature of wall-bounded flows transitioning to/from turbulence is the large-scale ordered coexistence of laminar and turbulent flow over a wide range of Reynolds numbers. In their article, Chantry et al. (J. Fluid Mech., vol. 791, 2016, R8) circumvent the problem of turbulence modulation in genuine plane Couette flow by replacing no-slip boundary conditions at the walls with effective stress-free conditions constraining the interior part of the flow only. In so doing, they are able to collect relevant information on the laminar–turbulent patterning. The approach is then adapted to plane Poiseuille and pipe flow, giving to it a more universal value. Taking advantage of the stress-free conditions, they derive reduced models efficient at capturing the laminar–turbulent coexistence. Such models would be useful to interpret recent findings in the large-aspect-ratio limit.
Turbulent energy flux generated by shock/homogeneous-turbulence interaction
Authors: Quadros Russell , Sinha Krishnendu , Larsson Johan
Published: April 2016

High-speed turbulent flows with shock waves are characterized by high localized surface heat transfer rates. Computational predictions are often inaccurate due to the limitations in modelling of the unclosed turbulent energy flux in the highly non-equilibrium regions of shock interaction. In this paper, we investigate the turbulent energy flux generated when homogeneous isotropic turbulence passes through a nominally normal shock wave. We use linear interaction analysis where the incoming turbulence is idealized as being composed of a collection of two-dimensional planar vorticity waves, and the shock wave is taken to be a discontinuity. The nature of the postshock turbulent energy flux is predicted to be strongly dependent on the angle of incidence of the incoming waves. The energy flux correlation is also decomposed into its vortical, entropy and acoustic contributions to understand its rapid non-monotonic variation behind the shock. Three-dimensional statistics, calculated by integrating two-dimensional results over a prescribed upstream energy spectrum, are compared with available data from direct numerical simulations. A detailed budget of the governing equation is also considered in order to gain insight into the underlying physics.
Physicochemical controls on biogeographic variation of benthic foraminiferal test size and shape
Authors: Keating-Bitonti Caitlin R. , Payne Jonathan L.
Published: April 2016

The sizes and shapes of marine organisms often vary systematically across latitude and water depth, but the environmental factors that mediate these gradients in morphology remain incompletely understood. A key challenge is isolating the individual contributions of many, often correlated, environmental variables of potential biological significance. Benthic foraminifera, a diverse group of rhizarian protists that inhabit nearly all marine environments, provide an unparalleled opportunity to test statistically among the various potential controls on size and volume–to–surface area ratio. Here, we use 7035 occurrences of 541 species of Rotallid foraminifera across 946 localities spanning more than 60 degrees of latitude and 1600 m of water depth around the North American continental margin to assess the relative influences of temperature, oxygen availability, carbonate saturation, and particulate organic carbon flux on their test volume and volume–to–surface area ratio. For the North American data set as a whole, the best model includes temperature and dissolved oxygen concentration as predictors. This model also applies to data from the Pacific continental margin in isolation, but only temperature is included in the best model for the Atlantic. Because these findings are consistent with predictions from the first principles of cell physiology, we interpret these statistical associations as the expressions of physiological selective pressures on test size and shape from the physical environment. Regarding existing records of temporal variation in foraminiferal test size across geological time in light of these findings suggests that the importance of temperature variation on the evolution of test volume and volume–to–surface area ratio may be underappreciated. In particular, warming may have played as important a role as reduced oxygen availability in causing test size reduction during past episodes of environmental crisis and is expected to inflict metabolic stress on benthic foraminifera over the next century due to anthropogenic climate change.
Making music on the march: sledging songs of the ‘heroic age’ of Antarctic exploration
Authors: Philpott Carolyn , Leane Elizabeth
Published: April 2016

During the so-called ‘heroic age’ of Antarctic exploration (c.1897–1922), various parties of men invented songs to aid the act of sledging and to provide a mental diversion from the monotony of the task and the physical demands it made on the human body. Songs composed in this uniquely polar musical genre typically included rhyming lyrics that were highly motivational and expressed a united identity. The lyrics were usually set to the melodies of popular songs of the day. When voiced in unison by men out ‘on the march,’ sledging songs could help to promote team synchronisation and cohesion, and give the act of sledging (as well as the expeditions as a whole) a stronger sense of purpose and meaning. The singing of such songs, therefore, contributed in a very practical way to the overall success of many Antarctic expeditions of the ‘heroic age’. This article examines three sledging songs dating from this period of Antarctic exploration and investigates the historical context in which they were created and performed. It also considers what these songs reveal about the experiences of the men who participated in the sledging journeys and their earliest perceptions of the Antarctic environment.
Older male and female drivers in car-dependent settings: how much do they use other modes, and do they compensate for reduced driving to maintain mobility?
Authors: KING MARK J. , SCOTT-PARKER BRIDIE J.
Published: April 2016

Among the societal and health challenges of population ageing is the continued transport mobility of older people who retain their driving licence, especially in highly car-dependent societies. While issues surrounding loss of a driving licence have been researched, less attention has been paid to variations in physical travel by mode among the growing proportion of older people who retain their driving licence. It is unclear how much they reduce their driving with age, the degree to which they replace driving with other modes of transport, and how this varies by age and gender. This paper reports research conducted in the state of Queensland, Australia, with a sample of 295 older drivers (>60 years). Time spent driving is considerably greater than time spent as a passenger or walking across age groups and genders. A decline in travel time as a driver with increasing age is not redressed by increases in travel as a passenger or pedestrian. The patterns differ by gender, most likely reflecting demographic and social factors. Given the expected considerable increase in the number of older women in particular, and their reported preference not to drive alone, there are implications for policies and programmes that are relevant to other car-dependent settings. There are also implications for the health of older drivers, since levels of walking are comparatively low.
Dancing the Pluriverse: Indigenous Performance as Ontological Praxis
Authors: Firmino Castillo María Regina
Published: April 2016

This article discusses ways that Indigenous dance is an ontological praxis that is embodied and telluric, meaning “of the earth.” It looks at how dancing bodies perform in relationship to ecosystems and entities within them, producing ontological distinctions and hierarchies that are often imbued with power. This makes dance a site of ontological struggle that potentially challenges the delusional ontological universality undergirding imperialism, genocide, and ecocide. The author explores these theoretical propositions through her participation in Oxlaval Q'anil, an emerging Ixil Maya dance project in Guatemala, and Dancing Earth, an itinerant and inter-tribal U.S.-based company founded by Rulan Tangen eleven years ago.
Culture Creators and Interconnected Individualism: Rulan Tangen and Anne Pesata's Basket Weaving Dance
Authors: Blu Wakpa Tria
Published: April 2016

This article meditates on the interconnectedness of the making and meaning of an Indigenous contemporary dance work that draws on intergenerational Jicarilla Apache basket weaving practices. Rulan Tangen choreographed the piece, performed by Anne Pesata, which is inspired by Pesata's lived experiences as a Jicarilla Apache woman and fifth generation basket weaver. Tangen—who identifies as mixed culturally, including Native, Polynesian, and European heritages—founded and directs Dancing Earth: Indigenous Contemporary Dance Creations, an intertribal company which originated in 2004. Tangen created the piece in February 2014 to honor Pesata and other Indigenous women leaders. The choreographer's commitment to undertaking projects that respond to Native elders' contemporary concerns and dancers' interests also guides its themes. Alongside music, the piece uses recorded voiceover that Pesata created and spoke. The voiceover makes transparent Pesata's familial connections with basket weaving and other Jicarilla Apache epistemologies and practices. The dance also elucidates relationships between basket weaving and Pesata's movements throughout, culminating in the creation of a figurative basket. According to Pesata, the dance “tells the story of the journey that you go through in making a basket from start to finish.”
Ohlone Profiles: A Brief Report on Some Currents of Native American Dance in Northern California
Authors: MacLean Neil
Published: April 2016

In this piece, co-director of the Ohlone Profiles project Neil MacLean relates experiences from his personal involvement over the last seven years producing Ohlone, Miwok and Pomo dance in San Francisco. Maclean offers an account of the renewal of Ohlone dance since the 1970s emphasizing how space for renewal was created by the Red Power movement and is activated by Ohlone, Miwok, and Pomo dance group leaders. MacLean argues for increased support for Indigenous culture from the city of San Francisco.
Dreaming the Fourth Hill
Authors: Jones Daystar/Rosalie
Published: April 2016

Dancer. Teacher. Choreographer. Writer. Passionate Amateur Mime and Mask-Maker. Wannabe Puppeteer. Founder, Director of Daystar: Contemporary Dance-Drama of Indian America. Acknowledged ‘pioneer’ of native modern dance USA. My father's insight: One day you will realize that you were blessed to be a descendant of the original peoples of this land.
My Making of We Wait in the Darkness
Authors: Simas Rosy
Published: April 2016

I am a performer working primarily as a choreographer. My approach to dance making is multi-faceted – I design immersive containers for performance using sound, textiles, film, and paper.
Teacher perceptions of teaching and learning English as a lingua franca in the expanding circle: A study of Taiwan
Authors: Luo Wen-Hsing
Published: April 2016

This study examines Taiwanese English teachers’ perceptions of English as a lingua franca (ELF) in relation to English teaching in classrooms. The definition of ELF is: English used as a lingual medium of communication among people of different linguacultural backgrounds (Jenkins, 2009: 200). Concerning the use of English, Taiwan is regarded as a country of ‘the expanding circle’ (Kachru, 1985, 1992), where English is not an official language, but is learned as a foreign language (EFL) at school and is considered essential for international communication. In Taiwan, English has been traditionally taught as a school subject and learners rarely have opportunities to use English outside the classroom, whereas the design of English pedagogy and curricula in Taiwan, following an EFL approach, is based on native-speaker (NS) norms with the aim of helping learners achieve native-like competence (cf. Suzuki, 2011). Due to the global spread of English, the majority of users of English for international communication are non-native speakers (non-NSs) (Crystal, 1997; Graddol, 1997, 2006); non-NSs of English now outnumber their native-speaker counterparts. In the global context, second language (L2) learners of English will mostly encounter non-NSs, whose ‘Englishes’ might deviate from NS English usage. Traditional EFL approaches to English teaching, which favor NS norms, may not ‘adequately prepare’ L2 learners of English to effectively interact and communicate with speakers ‘from other English-speaking contexts’ (Matsuda & Friedrich, 2011: 332). It has become important that English curricula and instruction are designed to prepare English learners to cope with international communication in which English variations are evident.
Mamluk authorities and Anatolian realities: Jānibak al-Ṣūfī, sultan al-Ashraf Barsbāy, and the story of a social network in the Mamluk/Anatolian frontier zone, 1435–1438
Authors: ADRIAENSSENS VEERLE , VAN STEENBERGEN JO
Published: April 2016

This article engages with the 838–841/1435–1437 Anatolian adventures of the Mamluk amir Jānibak al-Ṣūfī. It demonstrates how Jānibak's narrative is a remarkable story full of meanings, which enable a more nuanced understanding of Mamluk engagements with southern and eastern Anatolia during the reign of sultan al-Ashraf Barsbāy (825–41/1422–38). First Jānibak's whereabouts in Anatolia are reconstructed on the one hand as they appear from contemporary source material and as they have been analysed in a handful of modern studies on the other. Against this historiographical background, a more comprehensive understanding of Jānibak's role and significance is then developed, combining local, Syro-Egyptian and Anatolian readings of Jānibak's story into one integrated social network approach. This reconstruction of Jānibak's social network in the Anatolian frontier zone finally leads to a number of conclusions on the complexity of political life in the 1430s in eastern Anatolia, on the nature of Barsbāy's state, and on the shared realities of 15th-century political cultures in the Nile-to-Black-Sea area.
Mīrkhwānd and Persian Historiography
Authors: ANSARI ALI M.
Published: April 2016

Pre-modern historians of the Persianate world have primarily been used by modern historians as sources of factual information and rarely to gain insight into the means, methods and world-views of the historians themselves. The 15thC Persian historian Mīrkhwānd is a case in point despite the fact that his extensive discussion on the utility of history lends itself well to an historiographical assessment. While his understanding of the purpose of history may differ in some aspects for the modern discipline, his concerns and application were not as distinctive as we might like to think.
The Testimony of the Russian ‘Archbishop’ Peter Concerning the Mongols (1244/5): Precious Intelligence or Timely Disinformation?
Authors: JACKSON PETER
Published: April 2016

The first decade of the 21st century proved remarkably fertile in yielding up manuscripts relevant to the earliest direct contacts between Latin Europe and the Mongol empire – namely, those framed by the devastation of Rus´ (1237-40), Poland, Moravia and Hungary (1241-2) by the Mongols (or ‘Tartars’) and the subsequent despatch to the Mongol world of three parties of friars (1245-7) as envoys of Pope Innocent IV. These texts include:- (1) an early manuscript of theEpistula de vita secta et origine Tartarorumof the Hungarian Dominican Julian, who travelled to the Ural region in 1236–7 in search of the Hungarians’ pagan kinsmen in what was known as ‘Greater Hungary’, and returned with news of the imminent Mongol assault on Rus´; (2) two hitherto unknown letters from the Nestorian monk Simeon Rabban-ata to the Emperor Frederick II and King Louis IX of France, brought back from Azerbaijan in 1247 by one of Innocent IV's envoys, the Dominican André de Longjumeau; and (3) a second copy of the so-called ‘Tartar Relation’, an account produced in Poland in mid July 1247 by a Franciscan friar calling himself ‘C. de Bridia’ and closely linked with the most celebrated of the papal embassies to the Mongols, which was led by the Franciscan John of Plano Carpini and travelled across the Eurasian steppes as far as the court of the Qaghan Güyük in Mongolia.
Weight status, fatness and body image perception of North African immigrant women in Italy
Authors: Gualdi-Russo Emanuela , Rinaldo Natascia , Khyatti Meriem , Lakhoua Chérifa , Toselli Stefania
Published: April 2016

Objective

To investigate the nutritional status of North African (NA) immigrant women in Italy, analysing their body size, adiposity and body image perception in comparison to Italian natives and NA residents.

Design

The study utilized a cross-sectional design. Anthropometric traits were directly measured and a few indices were computed as proxy measures of nutritional status and adiposity. Body image perception was assessed using silhouette drawings. ANCOVA, adjusted for age, was used to compare anthropometric traits among different groups of women and the χ2 test to analyse differences in the prevalence of nutritional status.

Setting

Italy and North Africa (Tunisia, Morocco).

Subjects

A sample of 433 women aged 18–60 years old: NA immigrants (n 105); Italians (n 100); Tunisians (n 104); Moroccans (n 124).

Results

Overweight/obesity prevalence was very high in immigrants (79·8 %). Immigrants had the highest BMI value, the greatest hip circumference and mid upper-arm circumference. Their triceps skinfold thickness was significantly higher than that of Italians, but lower than that of NA residents.

Conclusions

NA immigrant women in Italy showed a higher incidence of overweight compared with Italians and NA residents. All groups showed a preference for a thinner body in comparison to their actual bodies and the immigrants are the most dissatisfied. Immigrants remain a high-risk group for obesity. Assessment of their body composition and health risk profile should be improved by using specific anthropometric measures that are easy to collect even in the case of large migration flows.
Stunting coexisting with overweight in 2·0–4·9-year-old Indonesian children: prevalence, trends and associated risk factors from repeated cross-sectional surveys
Authors: Rachmi Cut Novianti , Agho Kingsley Emwinyore , Li Mu , Baur Louise Alison
Published: April 2016

Objective

The persistence of undernutrition, along with overweight and obesity, constitute the double burden of malnutrition. The present study aimed to: (i) describe the prevalence and trends of concurrent stunting and overweight in Indonesian children; (ii) identify potentially associated risk factors; and (iii) determine whether stunted children are at greater risk of overweight compared with those of healthy height.

Design

A secondary data analysis of children aged 2·0–4·9 years in four cross-sectional studies of the Indonesian Family Life Survey. Children’s height and BMI Z-scores were calculated based on the WHO Child Growth Standards (2006). We defined ‘concurrent stunting and overweight’ as height-for-age Z-score <−2 and BMI Z-score >+1. Multivariate generalised linear latent and mixed models were used to determine associated risk factors.

Setting

Thirteen out of twenty-seven provinces in Indonesia.

Subjects

Children (n 4101) from four waves of the Indonesian Family Life Survey (1993–2007).

Results

There were inconsistent trends in the prevalence of concurrent stunting and overweight from waves 1 to 4. Children were more likely to be stunted and overweight when they were in the youngest age group (2·0–2·9 years), were weaned after the age of 6 months, had short-statured mothers or lived in rural areas. Stunted children were significantly more likely to be overweight than healthy-height children (OR>1) but did not differ significantly different across each wave (OR=1·34–2·01).

Conclusions

Concurrent stunting and overweight occurs in Indonesian children aged 2·0–4·9 years. Current policies and programmes need to be tailored for the management of this phenomenon.
Non-Precluded Measures Provisions in Bilateral Investment Treaties of South Asian Countries
Authors: SINHA Amit Kumar
Published: April 2016

This paper provides a first-ever detailed study of NPM provisions in all stand-alone BITs which are in force in South Asian countries. It studies 147 BITs of South Asian countries in order to map the NPM provisions in them. It makes an in-depth analysis of the NPM provisions found in these BITs, and then makes an analysis of the consequences of not having NPM provisions in BITs. This follows the dissection of the NPM provisions found, so as to study each and every permissible objective and nexus requirement link in these provisions. This is followed by suggestions and conclusions, where the paper holds that NPM provisions are not sufficiently used in the BITs of these countries and these countries should incorporate this provision more frequently in order to ensure some much-needed regulatory latitude to these countries.
Anforderungen an die qualifizierte Entzugsbehandlung bei Kindern und Jugendlichen
Authors: Thomasius Rainer , Thoms Edelhard , Melchers Peter , Roosen-Runge Gotthard , Schimansky Gisela , Bilke-Hentsch Oliver , Reis Olaf
Published: April 2016

Zusammenfassung. Zielsetzung: Die Gemeinsame Suchtkommission der kinder- und jugendpsychiatrischen Fachgesellschaft und der Fachverbände (Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie sowie Bundesarbeitsgemeinschaft der leitenden Klinikärzte für Kinder- und Jugendpsychiatrie, Psychotherapie und Psychosomatik und Berufsverband der Ärzte für Kinder- und Jugendpsychiatrie, Psychotherapie und Psychosomatik) legt eine konsentierte Stellungnahme zu den Anforderungen, die an eine Qualifizierte Entzugsbehandlung bei Kindern und Jugendlichen zu stellen sind vor. Therapie und Angebotsstruktur: Ziele der Qualifizierten Entzugsbehandlung sind neben der Bewältigung von Entzugssymptomen das Erreichen von Krankheitseinsicht, die Vermittlung erster Strategien im Umgang mit der Suchterkrankung sowie die Motivierung zur Inanspruchnahme weiterführender Behandlung. Hohe Komorbididtätsraten und polytoxikomane Konsummuster machen neben der suchtmedizinischen Qualifikation die Anwendung multiprofessioneller und multimodaler kinder- und jugendpsychiatrischer und -psychotherapeutischer Interventionen erforderlich. Schlussfolgerungen: Die Durchführung von Entzugsmaßnahmen bei Minderjährigen soll kinder- und jugendpsychiatrische und -psychotherapeutische Standards erfüllen. Die Behandlung suchtkranker Kinder und Jugendlicher sollte nicht gemeinsam mit Patienten erfolgen, die wegen anderer psychiatrischer Störungsbilder stationär aufgenommen werden.
CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells
Authors: Drachsler M , Kleber S , Mateos A , Volk K , Mohr N , Chen S , Cirovic B , Tüttenberg J , Gieffers C , Sykora J , Wirtz C R , Mueller W , Synowitz M , Martin-Villalba A
Published: April 2016

Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non-tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy.
Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism
Authors: Kamimura Naomi , Ichimiya Harumi , Iuchi Katsuya , Ohta Shigeo
Published: April 2016

We previously reported that molecular hydrogen (H2) acts as a novel antioxidant to exhibit multiple functions. Moreover, long-term drinking of H2-water (water infused with H2) enhanced energy expenditure to improve obesity and diabetes in db/db mice accompanied by the increased expression of fibroblast growth factor 21 (FGF21) by an unknown mechanism. H2 was ingested by drinking of H2-water or by oral administration of an H2-producing material, MgH2. The comprehensive gene expression profile in the liver of db/db mice was analyzed by DNA microarray. The molecular mechanisms underlying the gene expression profile was investigated using cultured HepG2 cells. Moreover, the effects on lifespan of drinking H2-water were examined using wild-type mice that were fed a fatty diet. Pathway analyses based on comprehensive gene expression revealed the increased expression of various genes involved in fatty acid and steroid metabolism. As a transcription pathway, the PPARα signaling pathway was identified to upregulate their genes by ingesting H2. As an early event, the gene expression of PGC-1α was transiently increased, followed by increased expression of FGF21. The expression of PGC-1α might be regulated indirectly through sequential regulation by H2, 4-hydroxy-2-nonenal, and Akt/FoxO1 signaling, as suggested in cultured cell experiments. In wild-type mice fed the fatty diet, H2-water improved the level of plasma triglycerides and extended their average of lifespan. H2 induces expression of the PGC-1α gene, followed by stimulation of the PPARα pathway that regulates FGF21, and the fatty acid and steroid metabolism.
Screening and identification of DNA aptamers toward Schistosoma japonicum eggs via SELEX
Authors: Long Yuqian , Qin Zhiqiang , Duan Minlan , Li Shizhu , Wu Xiaoqiu , Lin Wei , Li Jianglin , Zhao Zilong , Liu Jing , Xiong Dehui , Huang Yi , Hu Xiaoxiao , Yang Chao , Ye Mao , Tan Weihong
Published: April 2016

Schistosomiasis is a major parasitic disease caused by blood flukes of the genus Schistosoma. Several million people all over the world are estimated to suffer from severe morbidity as a consequence of schistosomiasis. The worm’s eggs, which cause the symptoms of schistosomiasis, are generally used to diagnose the disease. In this study, we employed egg-based systematic evolution of ligands by exponential enrichment (egg-SELEX) and identified a panel of ssDNA aptamers specifically binding to eggs derived from S. japonicum. Among these, two aptamers LC6 and LC15 exhibited strong binding to and specific recognition of S. japonicum eggs, but not eggs from Fasciolopsis buski, Enterobius, Ascaris or Clonorchis sinensis. Furthermore, tissue imaging results revealed that LC15 could recognize S. japonicum eggs laid in liver tissues with a detection ratio of 80.5%. Collectively, therefore, we obtained useful aptamers specifically recognizing S. japonicum eggs, which will facilitate the development of an effective tool for both schistosomiasis diagnosis and drug delivery.
Unravelling and controlling hidden imprint fields in ferroelectric capacitors
Authors: Liu Fanmao , Fina Ignasi , Bertacco Riccardo , Fontcuberta Josep
Published: April 2016

Ferroelectric materials have a spontaneous polarization that can point along energetically equivalent, opposite directions. However, when ferroelectric layers are sandwiched between different metallic electrodes, asymmetric electrostatic boundary conditions may induce the appearance of an electric field (imprint field, Eimp) that breaks the degeneracy of the polarization directions, favouring one of them. This has dramatic consequences on functionality of ferroelectric-based devices such as ferroelectric memories or photodetectors. Therefore, to cancel out the Eimp, ferroelectric components are commonly built using symmetric contact configuration. Indeed, in this symmetric contact configuration, when measurements are done under time-varying electric fields of relatively low frequency, an archetypical symmetric single-step switching process is observed, indicating Eimp ≈ 0. However, we report here on the discovery that when measurements are performed at high frequency, a well-defined double-step switching is observed, indicating the presence of Eimp. We argue that this frequency dependence originates from short-living head-to-head or tail-to-tail ferroelectric capacitors in the device. We demonstrate that we can modulate Eimp and the life-time of head-to-head or tail-to-tail polarization configurations by adjusting the polarization screening charges by suitable illumination. These findings are of relevance to understand the effects of internal electric fields on pivotal ferroelectric properties, such as memory retention and photoresponse.
The early history and emergence of molecular functions and modular scale-free network behavior
Authors: Aziz M. Fayez , Caetano-Anollés Kelsey , Caetano-Anollés Gustavo
Published: April 2016

The formation of protein structural domains requires that biochemical functions, defined by conserved amino acid sequence motifs, be embedded into a structural scaffold. Here we trace domain history onto a bipartite network of elementary functional loop sequences and domain structures defined at the fold superfamily level of SCOP classification. The resulting ‘elementary functionome’ network and its loop motif and structural domain graph projections create evolutionary ‘waterfalls’ describing the emergence of primordial functions. Waterfalls reveal how ancient loops are shared by domain structures in two initial waves of functional innovation that involve founder ‘p-loop’ and ‘winged helix’ domain structures. They also uncover a dynamics of modular motif embedding in domain structures that is ongoing, which transfers ‘preferential’ cooption properties of ancient loops to emerging domains. Remarkably, we find that the emergence of molecular functions induces hierarchical modularity and power law behavior in network evolution as the network of motifs and structures expand metabolic pathways and translation.
Glass-on-Glass Fabrication of Bottle-Shaped Tunable Microlasers and their Applications
Authors: Ward Jonathan M. , Yang Yong , Nic Chormaic Síle
Published: April 2016

We describe a novel method for making microbottle-shaped lasers by using a CO2 laser to melt Er:Yb glass onto silica microcapillaries or fibres. This is realised by the fact that the two glasses have different melting points. The CO2 laser power is controlled to flow the doped glass around the silica cylinder. In the case of a capillary, the resulting geometry is a hollow, microbottle-shaped resonator. This is a simple method for fabricating a number of glass whispering gallery mode (WGM) lasers with a wide range of sizes on a single, micron-scale structure. The Er:Yb doped glass outer layer is pumped at 980 nm via a tapered optical fibre and WGM lasing is recorded around 1535 nm. This structure facilitates a new way to thermo-optically tune the microlaser modes by passing gas through the capillary. The cooling effect of the gas flow shifts the WGMs towards shorter wavelengths and thermal tuning of the lasing modes over 70 GHz is achieved. Results are fitted using the theory of hot wire anemometry, allowing the flow rate to be calibrated with a flow sensitivity as high as 72 GHz/sccm. Strain tuning of the microlaser modes by up to 60 GHz is also demonstrated.
Experimental evidence of coherent transport
Authors: Flores-Olmedo E. , Martínez-Argüello A. M. , Martínez-Mares M. , Báez G. , Franco-Villafañe J. A. , Méndez-Sánchez R. A.
Published: April 2016

Coherent transport phenomena are difficult to observe due to several sources of decoherence. For instance, in the electronic transport through quantum devices the thermal smearing and dephasing, the latter induced by inelastic scattering by phonons or impurities, destroy phase coherence. In other wave systems, the temperature and dephasing may not destroy the coherence and can then be used to observe the underlying wave behaviour of the coherent phenomena. Here, we observe coherent transmission of mechanical waves through a two-dimensional elastic Sinai billiard with two waveguides. The flexural-wave transmission, performed by non-contact means, shows the quantization when a new mode becomes open. These measurements agree with the theoretical predictions of the simplest model highlighting the universal character of the transmission fluctuations.
Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma
Authors: Gedye Craig , Sirskyj Danylo , Lobo Nazleen C. , Meens Jalna , Hyatt Elzbieta , Robinette Michael , Fleshner Neil , Hamilton Robert J , Kulkarni Girish , Zlotta Alexandre , Evans Andrew , Finelli Antonio , Jewett Michael A. S. , Ailles Laurie E.
Published: April 2016

Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ−/− (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers.
GPR40 agonist ameliorates liver X receptor-induced lipid accumulation in liver by activating AMPK pathway
Authors: Li Meng , Meng Xiangyu , Xu Jie , Huang Xiuqing , Li Hongxia , Li Guoping , Wang Shu , Man Yong , Tang Weiqing , Li Jian
Published: April 2016

Hepatic steatosis is strongly linked to insulin resistance and type 2 diabetes. GPR40 is a G protein-coupled receptor mediating free fatty acid-induced insulin secretion and thus plays a beneficial role in the improvement of diabetes. However, the impact of GPR40 agonist on hepatic steatosis still remains to be elucidated. In the present study, we found that activation of GPR40 by its agonist GW9508 attenuated Liver X receptor (LXR)-induced hepatic lipid accumulation. Activation of LXR in the livers of C57BL/6 mice fed a high-cholesterol diet and in HepG2 cells stimulated by chemical agonist caused increased expression of its target lipogenic genes and subsequent lipid accumulation. All these effects of LXR were dramatically downregulated after GW9508 supplementation. Moreover, GPR40 activation was accompanied by upregulation of AMPK pathway, whereas the inhibitive effect of GPR40 on the lipogenic gene expression was largely abrogated by AMPK knockdown. Taken together, our results demonstrated that GW9508 exerts a beneficial effect to ameliorate LXR-induced hepatic steatosis through regulation of AMPK signaling pathway.
Ultrafast Imaging using Spectral Resonance Modulation
Authors: Huang Eric , Ma Qian , Liu Zhaowei
Published: April 2016

CCD cameras are ubiquitous in research labs, industry and hospitals for a huge variety of applications, but there are many dynamic processes in nature that unfold too quickly to be captured. Although tradeoffs can be made between exposure time, sensitivity and area of interest, ultimately the speed limit of a CCD camera is constrained by the electronic readout rate of the sensors. One potential way to improve the imaging speed is with compressive sensing (CS), a technique that allows for a reduction in the number of measurements needed to record an image. However, most CS imaging methods require spatial light modulators (SLMs), which are subject to mechanical speed limitations. Here, we demonstrate an etalon array based SLM without any moving elements that is unconstrained by either mechanical or electronic speed limitations. This novel spectral resonance modulator (SRM) shows great potential in an ultrafast compressive single pixel camera.
High prevalence of vaterite in sagittal otoliths causes hearing impairment in farmed fish
Authors: Reimer T. , Dempster T. , Warren-Myers F. , Jensen A. J. , Swearer S. E.
Published: April 2016

The rapid growth of aquaculture raises questions about the welfare status of mass-produced species. Sagittal otoliths are primary hearing structures in the inner ear of all teleost (bony) fishes and are normally composed of aragonite, though abnormal vaterite replacement is sometimes seen in the wild. We provide the first widespread evaluation of the prevalence of vaterite in otoliths, showing that farmed fish have levels of vaterite replacement over 10 times higher than wild fish, regardless of species. We confirm this observation with extensive sampling of wild and farmed Atlantic salmon in Norway, the world’s largest producer and verify that vateritic otoliths are common in farmed salmon worldwide. Using a mechanistic model of otolith oscillation in response to sound, we demonstrate that average levels of vaterite replacement result in a 28–50% loss of otolith functionality across most of a salmonid’s known hearing range and throughout its life cycle. The underlying cause(s) of vaterite formation remain unknown, but the prevalence of hearing impairment in farmed fish has important implications for animal welfare, the survival of escapees and their effects on wild populations and the efficacy of restocking programs based on captive-bred fish.
In-situ Liquid Phase Epitaxy: Another Strategy to Synthesize Heterostructured Core-shell Composites
Authors: Wen Zhongsheng , Wang Guanqin
Published: April 2016

Core-shell Nb2O5/TiO2 composite with hierarchical heterostructure is successfully synthesized In-situ by a facile template-free and acid-free solvothermal method based on the mechanism of liquid phase epitaxy. The chemical circumstance change induced by the alcoholysis of NbCl5 is utilized tactically to trigger core-shell assembling In-situ. The tentative mechanism for the self-assembling of core-shell structure and hierarchical structure is explored. The microstructure and morphology changes during synthesis process are investigated systematically by using X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy and transmission electron microscopy. The dramatic alcoholysis of NbCl5 has been demonstrated to be the fundamental factor for the formation of the spherical core, which changes the acid circumstance of the solution and induces the co-precipitation of TiO2. The homogeneous co-existence of Nb2O5/TiO2 in the core and the co-existence of Nb/Ti ions in the reaction solution facilitate the In-situ nucleation and epitaxial growth of the crystalline shell with the same composition as the core. In-situ liquid phase epitaxy can offer a different strategy for the core-shell assembling for oxide materials.
Pain tolerance predicts human social network size
Authors: Johnson Katerina V.-A. , Dunbar Robin I. M.
Published: April 2016

Personal social network size exhibits considerable variation in the human population and is associated with both physical and mental health status. Much of this inter-individual variation in human sociality remains unexplained from a biological perspective. According to the brain opioid theory of social attachment, binding of the neuropeptide β-endorphin to μ-opioid receptors in the central nervous system (CNS) is a key neurochemical mechanism involved in social bonding, particularly amongst primates. We hypothesise that a positive association exists between activity of the μ-opioid system and the number of social relationships that an individual maintains. Given the powerful analgesic properties of β-endorphin, we tested this hypothesis using pain tolerance as an assay for activation of the endogenous μ-opioid system. We show that a simple measure of pain tolerance correlates with social network size in humans. Our results are in line with previous studies suggesting that μ-opioid receptor signalling has been elaborated beyond its basic function of pain modulation to play an important role in managing our social encounters. The neuroplasticity of the μ-opioid system is of future research interest, especially with respect to psychiatric disorders associated with symptoms of social withdrawal and anhedonia, both of which are strongly modulated by endogenous opioids.