bluuebunny/crossref_metadata_2025 huggingface dataset:
Forging Paths for the African Queer: Is There an “African” Mechanism for Realizing LGBTIQ Rights?
Authors: Devji Zahrah Z
Published: September 2016

The African continent has struggled to accept its LGBTIQ population and queer individuals continue to struggle in pursuit of their rights. Similar refrains justifying widespread homophobia reverberate throughout the continent. This article analyses two case studies in Africa: Uganda and South Africa. Although each country treats the question of queer rights differently, arguably the treatment of the queer on a day to day basis is not dissimilar in each country. The article considers whether there is a mechanism for realizing queer rights in Africa, by appealing to the values and cultures that exist on the continent.
No-tillage culture and nitrogen fertilizer management for burley tobacco production
Authors: ZOU C. , PEARCE R. C. , GROVE J. H. , COYNE M. S.
Published: September 2016

Few studies have investigated nitrogen (N) fertilizer management in no-tillage (NT) tobacco (Nicotiana tobacumL.) production systems, even though N fertilization is known to influence tobacco cured leaf yield and quality. The present study evaluated how tillage practice and N fertilizer rate affected burley tobacco agronomic performance, plant available nitrogen (PAN) supply, and leaf chemical constituents. In 2012 and 2013, three N fertilizer rates (0, 140 and 280 kg N/ha) were introduced as split-plots within a long-term NT and conventional tillage (CT) (mouldboard plough) comparison study. Results (2007–2013) showed that the effect of tillage on tobacco yield depended on seasonal weather; NT tobacco appeared to have lower yield than CT tobacco in seasons with <450 mm growing season rainfall, but similar yields when rainfall was >500 mm. In 2012 (432 mm rainfall; 84% of the long-term seasonal mean), leaf SPAD reading, leaf nitrate concentration, total nitrogen concentration at the topping day (i.e. removal of flowers/buds at the tops of the plants) and cured leaf nicotine and alkaloid content suggested that N deficiency was more pronounced in NT than CT at the lowest N fertilizer rate. The PAN supply, as measured by a modifiedin situresin core method, was similar in 2012 between NT and CT, suggesting that plant factors may have had a role in N uptake efficiency. This scenario did not repeat in 2013 (706 mm rainfall; 137% of the long-term seasonal mean). Even though N fertilization rates were identical for both tillage practices in 2012 and 2013, PAN was lower, on average, in 2012. Because N uptake is largely the result of mass flow, the impact of reduced root density in NT tobacco would be expected to be more pronounced in a season such as 2012, when water was limited. Banding N close to the tobacco root system and/or side-dressing some portion of N may be recommended strategies to improve N use efficiency in NT burley tobacco production.
Therapeutic potential of the immunomodulatory proteins Wuchereria bancrofti L2 and Brugia malayi abundant larval transcript 2 against streptozotocin-induced type 1 diabetes in mice
Authors: Amdare N.P. , Khatri V.K. , Yadav R.S.P. , Tarnekar A. , Goswami K. , Reddy M.V.R.
Published: September 2016

Epidemiological and experimental evidence has supported the concept of using helminths as alternative bio-therapeutic agents in the treatment of type 1 diabetes (T1D). In the current study, two filarial proteins, recombinant Wuchereria bancrofti L2 (rWbL2) and Brugia malayi abundant larval transcript 2 (rBmALT-2) have been investigated, individually and in combination, for their therapeutic potential in streptozotocin (STZ)-induced T1D. The rWbL2 and rBmALT-2 proteins, when administered individually or in combination, have resulted in lowering of the blood glucose levels and reducing the incidence of T1D in mice. In addition, these proteins have led to reduced lymphocytic infiltration and decreased islet damage and inflammation. The curative effect was found to be associated with the suppression of release of tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and increased production of interleukin (IL)-4, IL-5 and IL-10 cytokines by the splenocytes of the diabetic mice. Insulin-specific IgG1 and antigen-specific IgE antibodies were found to be elevated in the sera of mice treated with rWbL2 and rBmALT-2 proteins. From the findings in this study, it can be envisaged that both of these filarial immunomodulatory proteins have the potential to ameliorate T1D by altering the regulatory immune responses.
Introduction: Transitions from late prehistory to early historic periods in mainland Southeast Asia, c. early to mid-first millennium CE
Authors: Murphy Stephen A. , Stark Miriam T.
Published: September 2016

Studies of early Southeast Asia focus largely on its ‘classical states’, when rulers and their entourages from Sukhothai and Ayutthaya (Thailand), Angkor (Cambodia), Bagan (Myanmar), Champa and Dai Viet (Vietnam) clashed, conquered, and intermarried one another over an approximately six-century-long quest for legitimacy and political control. Scholarship on Southeast Asia has long held that such transformations were largely a response to outside intervention and external events, or at least that these occurred in interaction with a broader world system in which Southeast Asians played key roles. As research gathered pace on the prehistory of the region over the past five decades or so, it has become increasingly clear that indigenous Southeast Asian cultures grew in sophistication and complexity over the Iron Age in particular. This has led archaeologists to propose much greater agency in regard to the selective adaptation of incoming Indic beliefs and practices than was previously assumed under early scholarship of the nineteenth and early to mid-twentieth century.
A skink out of water: impacts of anthropogenic disturbance on an Endangered reptile in Australian highland swamps
Authors: Gorissen Sarsha , Greenlees Matthew , Shine Richard
Published: September 2016

The Blue Mountains water skinkEulamprus leuraensisis an Endangered swamp specialist known from < 60 sites and restricted to the rare, threatened and fragmented habitat of Temperate Highland Peat Swamps on Sandstone. Understanding the species’ ecology, notably its vulnerability to threatening processes such as hydrological disturbance, is essential if we are to retain viable populations of this Endangered reptile. We examined the impact of anthropogenic disturbance (longwall mining practices, development (industrial, urban, infrastructural) and damage by recreational vehicles) on this species, other herpetofauna and the swamp by surveying six paired undisturbed and disturbed sites in south-eastern Australia. The abundance ofE. leuraensiswas severely affected by disturbance. The species was absent from disturbed swamps, where it was replaced by its congenerE. heatwoleiand other woodland reptile species. Disturbance was associated with a halving of soil moisture content and a loss of surface water; the dense, live understorey was replaced by a sparser, drier habitat with dead vegetation, logs, rocks and bare ground. In effect, disturbance eliminated the distinctive features of the swamp habitat, transforming it into an area that resembled the surrounding habitat in terms of fauna, flora and physical characteristics. Our surveys suggest that hydrological disturbance (groundwater loss or alterations in surface water chemistry) extirpatesE. leuraensis. This species' dependence on groundwater renders it sensitive to habitat degradation through hydrological disturbance. The conservation message for management authorities is clear: to protect the skink, protect the habitat.
Text trajectories in a multilingual call centre: The linguistic ethnography of a calling script
Authors: Woydack Johanna , Rampton Ben
Published: September 2016

Call centres have been widely criticised as standardised workplaces, and the imposition of calling scripts is often characterised as dehumanising and deskilling. But these accounts lack close analysis of how scripts are actually produced, taken up, and used by call-centre workers, and they are generally locked into dualistic analyses of control and resistance. In contrast, this article combines long-term ethnography with transcontextual analysis of the production, circulation and uptake of calling scripts. This reveals a good deal of collective and individual agency in processes of text-adaptation, and produces a rather more nuanced picture of work in a call centre. (Call centres, text trajectories, linguistic ethnography, standardisation)*
Dairy food products: good or bad for cardiometabolic disease?
Authors: Lovegrove Julie A. , Givens D. Ian
Published: September 2016

Prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasingly and is a key risk for CVD development, now recognised as the leading cause of death globally. Dietary strategies to reduce CVD development include reduction of saturated fat intake. Milk and dairy products are the largest contributors to dietary saturated fats in the UK and reduced consumption is often recommended as a strategy for risk reduction. However, overall evidence from prospective cohort studies does not confirm a detrimental association between dairy product consumption and CVD risk. The present review critically evaluates the current evidence on the association between milk and dairy products and risk of CVD, T2DM and the metabolic syndrome (collectively, cardiometabolic disease). The effects of total and individual dairy foods on cardiometabolic risk factors and new information on the effects of the food matrix on reducing fat digestion are also reviewed. It is concluded that a policy to lower SFA intake by reducing dairy food consumption to reduce cardiometabolic disease risk is likely to have limited or possibly negative effects. There remain many uncertainties, including differential effects of different dairy products and those of differing fat content. Focused and suitably designed and powered studies are needed to provide clearer evidence not only of the mechanisms involved, but how they may be beneficially influenced during milk production and processing.
Identification of Nanocrystalline Inclusions in Bismuth-Doped Silica Fibers and Preforms
Authors: Iskhakova Liudmila D. , Milovich Filipp O. , Mashinsky Valery M. , Zlenko Alexander S. , Borisovsky Sergey E. , Dianov Evgeny M.
Published: September 2016

The nature of nanocrystalline inclusions and dopant distribution in bismuth-doped silicate fibers and preforms are studied by scanning and transmission electron microscopy, and energy and wavelength-dispersive X-ray microanalysis. The core compositions are Bi:SiO2, Bi:Al2O3–SiO2, Bi:GeO2–SiO2, Bi:Al2O3–GeO2–SiO2, and Bi:P2O5–Al2O3–GeO2–SiO2. Nanocrystals of metallic Bi, Bi2O3, SiO2, GeO2, and Bi4(GeO4)3 are observed in these glasses. These inclusions can be the reason for the background optical loss in bismuth-doped optical fibers. The bismuth concentration of 0.0048±0.0006 at% is directly measured in aluminosilicate optical fibers with effective laser generation (slope efficiency of 27% at room temperature).
ON THE GENERATING GRAPH OF A SIMPLE GROUP
Authors: LUCCHINI ANDREA , MARÓTI ATTILA , RONEY-DOUGAL COLVA M.
Published: September 2016

The generating graph $\unicode[STIX]{x1D6E4}(H)$ of a finite group $H$ is the graph defined on the elements of $H$, with an edge between two vertices if and only if they generate $H$. We show that if $H$ is a sufficiently large simple group with $\unicode[STIX]{x1D6E4}(G)\cong \unicode[STIX]{x1D6E4}(H)$ for a finite group $G$, then $G\cong H$. We also prove that the generating graph of a symmetric group determines the group.
Legal Records at Risk: Does the Legal Profession Care about Preserving its Heritage? And What Could be Done to Rescue Private Sector Legal Records?
Authors: Cowling Clare
Published: September 2016

This article is written by Clare Cowling, Director, Legal Records at Risk Project, Institute of Advanced Legal Studies, University of London. Her article explores the hypothesis that modern private sector legal records are more at risk of loss than their historical equivalents. There are many reasons for this, but one factor, detailed in this article, appears to be the indifference or reluctance of legal practitioners themselves. The LRAR project seeks to allay any concerns practitioners may have about confidentiality and to raise their awareness of the potential commercial and historic value of their legal records. It will do this by a combination of case studies, interviews with stakeholders and investigations into the current information management and archiving practices of institutions specialised to law. In so doing it will provide guidance and advice on the more cost-effective management and preservation of legal records so that the history of change to non-governmental legal services in the UK over the past century will be accurately documented.
Reflections on the IALL Conference 2015 and Some Thoughts About Brexit: Perhaps Brexit is the Ending of the International Era and the Beginning of the Transnational Period?
Authors: Punch Pattie
Published: September 2016

In this article Pattie Punch reflects on IALL's 34th Annual Course on International Law and Legal Information which was held at Statsbibliothek, Berlin from 20th to 24th September, 2015. The course was entitled ‘Within and in Between: German Legal Tradition in Times of Internationalization and Beyond’ and the work and content of the presentations made her consider what she values about the education of law librarians in the 21st Century. The course raised many questions in relation to a resilient education for law librarians. Since this course, the Brexit referendum in the UK has taken place and the author offers her thoughts about this change of direction and what it might mean for the profession.
Reconstructing the Underclass
Authors: Macnicol John
Published: September 2016

In late 2011, the Conservative and Liberal Democrat coalition government announced the launch of a new programme on ‘troubled families’ – a term used to describe the estimated 120,000 most behaviourally anti-social families in England and Wales. To many social scientists, this appeared to be yet another reconstruction of the broad ‘underclass’ concept that has run like a thread of analysis through UK poverty discourses over the last 150 years. The symbolic nature and coded meanings of this particular concept of poverty are very interesting, as is the way it has been reconstructed periodically. This paper summarises these reconstructions, and the analytical issues raised by them: the ‘residuum’ concept of the 1880–1914 period; the ‘social problem group’ of the inter-war years; the ‘problem family’ of the 1940s and 1950s; the ‘cycle of deprivation’ of the 1970s; and the ‘underclass’ of the 1980s and 1990s.
Accuracy of the Distress Thermometer for home care patients with palliative care needs in Germany
Authors: Wüller Johannes , Küttner Stefanie , Foldenauer Ann Christina , Rolke Roman , Pastrana Tania
Published: September 2016

Objective:

Our aim was to examine the accuracy of the German version of the Distress Thermometer (DT) compared with the Hospital Anxiety and Depression Scale (HADS) in patients with palliative care needs living at home.

Method:

Ours was a 15-month cross-sectional study beginning in September of 2013 in Germany with consecutive patients cared for by a palliative home care service. The survey was implemented during the initial visit by a home care team. Patients were excluded if they were under 18 years of age, mentally or physically unable to complete the assessment questionnaires as judged by their healthcare worker, or unable to understand the German language. During the first encounter, the DT and HADS were applied, and sociodemographic and medical data were collected.

Results:

A total of 89 persons completed both the HADS and DT questionnaires (response rate = 59.7%; mean age = 67 years; female = 55.1%; married = 65.2%; living home with relatives = 73.0%; oncological condition = 92.1%; Karnofsky Performance Scale [KPS] score: 0–40 = 30.3%, 50–70 = 57.3%, >80 = 6.7%). The mean DT score was 6.3 (±2.3), with 84.3% of participants scoring above the DT cutoff (≥4). The mean HADStotalscore was 17.9 (±7.8), where 64% of participants had a total HADS score (HADStotal) ≥15, 51.7% reported anxiety (HADSanxiety≥ 8), and 73% reported depression (HADSdepression≥ 8). Using the HADS as a gold standard, a DT cutoff score ≥5 was optimal for identifying severe distress in patients with palliative care needs, with a sensitivity of 93.0%, a specificity of 34.4%, a positive predictive value (PPV) of 73.3%, and likelihood ratios LR+ = 1.42 (<3) and –LR = 0.203 (<0.3).

Significance of results:

The DT performed satisfactorily compared to the HADS in screening for distress in our study and can be employed as an instrument for identification of patients with distress. Consequent to the high prevalence of distress, we recommend its routine use for screening distressed persons at home with palliative care needs in order to offer adequate support.
Ambulante Dialektisch-Behaviorale Therapie für Adoleszente (DBT-A) mit impulsiven und selbstschädigenden Verhaltensweisen
Authors: Maffezzoni Marco , Steinhausen Hans-Christoph
Published: September 2016

Zusammenfassung. Die Dialektisch-Behaviorale Therapie für Adoleszente (DBT-A) zur Behandlung impulsiver und suizidaler Jugendlicher wird seit Februar 2005 in leicht abgeänderter Form ambulant im Kinder- und Jugendpsychiatrischen Dienst Zürich umgesetzt. Diese DBT-A umfasst Einzeltherapie, ein Gruppen- bzw. Skills-Training sowie einen Elternabend und dauert jeweils ein halbes Jahr. Der vorliegende Erfahrungsbericht zeigt die Umsetzung dieses Ansatzes und präsentiert eine Evaluation im Rahmen der klinikinternen Qualitätssicherung.

Die insgesamt 43 Teilnehmerinnen des Therapie-Programms waren weibliche Jugendliche im Alter von 14–19 Jahren, die impulsive und selbstschädigende Verhaltensweisen sowie Probleme in der Regulierung ihrer Emotionen und in der zwischenmenschlichen Beziehungsgestaltung aufwiesen. An einem Skills-Training nahmen jeweils 4–6 Jugendliche teil.

Unsere mehrheitlich positiven Erfahrungen mit diesem Ansatz in der Therapie wurden durch die Auswertungen der Daten aus der Qualitätssicherung von 19 Teilnehmerinnen bestätigt, welche sowohl Selbst- wie auch Fremdurteile umfassten. Es liegen Hinweise vor, dass die DBT-A mit zu einer Abnahme sowohl verschiedener Indikatoren der allgemeinen als auch der spezifischen Psychopathologie führt.
Pilotstudie zu psychiatrischen und sozialen Aspekten bei Kindern und Jugendlichen mit Fragilem-X-Syndrom (FRX)
Authors: Häßler Frank , Gaese Franziska , Colla Michael , Huss Michael , Kretschmar Christoph , Brinkman Marc , Peters Helmut , Elstner Samuel , Weirich Steffen , Pittrow David
Published: September 2016

Zusammenfassung. Fragestellung: Ziel der Untersuchung ist die Erhebung von Daten zu psychischen Belastungen und deren Behandlung bei Kindern und Jugendlichen mit Fragilem-X-Syndrom (FRX). Methodik: Die Ergebnisse basieren auf einer strukturierten, prospektiven, offenen, nichtinterventionellen, registerbasierten Beobachtungsstudie in Deutschland (EXPLAIN), im Rahmen derer an 11 Zentren 34 Patienten jünger als 18 Jahre mit einem genetisch gesicherten FRX eingeschlossen wurden. Ergebnisse: Jedes dritte Indexkind hatte ein ebenfalls unter FRX leidendes Geschwisterkind. Die Belastung mit neurologischen und psychischen Symptomen war insgesamt hoch, wobei ataktische Symptome, epileptische Anfälle und autistische Symptome nur bei den Kindern (< 14 Jahre) berichtet wurden. Nahezu alle erfassten psychischen Symptome und Störungen, insbesondere die expansiven Symptome, wurden mit entsprechenden Psychopharmaka behandelt. Darüber hinaus kamen oft logopädische, ergotherapeutische und heilpädagogische Maßnahmen zum Einsatz. Trotz der hohen Symptombelastung lebten 96.3 % der unter 14-Jährigen und immer noch 57.1 % der 14- bis 18-Jährigen im elterlichen Haushalt. Schlussfolgerungen: Aufgrund der hohen Belastung mit neurologischen und psychischen Symptomen sollte frühzeitig eine dem Alter entsprechende kinder- und jugendpsychiatrische und neurologische Diagnostik und Therapie erfolgen.
Verhaltenstherapeutische Intervention für Vorschulkinder mit Autismus
Authors: Molnár Claire , Eldevik Sigmund
Published: September 2016

Zusammenfassung. Fragestellung: Für Vorschulkinder mit Autismus-Spektrum-Störung (ASS) weist die frühe intensive Verhaltenstherapie die besten Lernerfolge auf. In dieser explorativen Studie wurden Ergebnisse eines Modells für ein Angebot auf kommunaler Ebene mit Eltern als aktive Therapeuten ausgewertet. Methodik: In einem Wartelisten-Kontrolldesign wurden 13 Kinder mit ASS, die zu Beginn der Intervention zwischen 2 und 5 Jahre alt waren, untersucht. Sie erhielten eine einjährige verhaltenstherapeutische Frühförderung von ca. 20 Wochenstunden im Elternhaus, größtenteils durchgeführt von ihren Eltern. Die Wartekontrollgruppe bestand aus sieben Kindern, die 6 Monate vor der Intervention untersucht wurden. Die Therapie wurde auf der Grundlage des University of California at Los Angeles Young Autism Project-Modells (UCLA YAP; Lovaas, 1981 , 1987 , 2003 ) durchgeführt. Zur Messung wurden die Testverfahren Psychoeducational Profile, Third Edition (PEP-3), Parenting Stress Index (PSI) und Childhood Autism Rating Scale, Second Edition (CARS2) eingesetzt. Aus dem Teilbereich Cognitive Verbal/Preverbal des PEP-3, der das mentale Entwicklungsalter misst, wurde zusätzlich ein mentaler Entwicklungsindex (MDI) errechnet. Ergebnisse: Nach einem Jahr intensiver Verhaltenstherapie wurden signifikant höhere PEP-3-Werte und ein signifikant höherer mentaler Entwicklungsindex gemessen. Es wurden außerdem signifikant niedrigere CARS2-Werte gemessen. Bei der Wartekontrollgruppe, gab es keine signifikanten Veränderungen. Das Stressniveau der Eltern veränderte sich nicht signifikant und sank insgesamt leicht. Schlussfolgerung: Diese Umsetzung der frühen intensiven Verhaltenstherapie ist vielversprechend. Die umfangreiche Elternbeteiligung an der Förderung zeigte keine besonderen Auswirkungen auf das Stresserleben der Eltern. Die Studie sollte mit einer größeren Stichprobe und einem verbesserten Design wiederholt werden.
The structural basis for CD36 binding by the malaria parasite
Authors: Hsieh Fu-Lien , Turner Louise , Bolla Jani Reddy , Robinson Carol V. , Lavstsen Thomas , Higgins Matthew K.
Published: September 2016

CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum, tethering parasite-infected erythrocytes to endothelial receptors. This prevents their destruction by splenic clearance and allows increased parasitaemia. Here we describe the structure of CD36 in complex with long chain fatty acids and a CD36-binding PfEMP1 protein domain. A conserved hydrophobic pocket allows the hugely diverse PfEMP1 protein family to bind to a conserved phenylalanine residue at the membrane distal tip of CD36. This phenylalanine is also required for CD36 to interact with lipoprotein particles. By targeting a site on CD36 that is required for its physiological function, PfEMP1 proteins maintain the ability to tether to the endothelium and avoid splenic clearance.
Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd
Authors: Wang Zichen , Monteiro Caroline D. , Jagodnik Kathleen M. , Fernandez Nicolas F. , Gundersen Gregory W. , Rouillard Andrew D. , Jenkins Sherry L. , Feldmann Axel S. , Hu Kevin S. , McDermott Michael G. , Duan Qiaonan , Clark Neil R. , Jones Matthew R. , Kou Yan , Goff Troy , Woodland Holly , Amaral Fabio M R. , Szeto Gregory L. , Fuchs Oliver , Schüssler-Fiorenza Rose Sophia M. , Sharma Shvetank , Schwartz Uwe , Bausela Xabier Bengoetxea , Szymkiewicz Maciej , Maroulis Vasileios , Salykin Anton , Barra Carolina M. , Kruth Candice D. , Bongio Nicholas J. , Mathur Vaibhav , Todoric Radmila D , Rubin Udi E. , Malatras Apostolos , Fulp Carl T. , Galindo John A. , Motiejunaite Ruta , Jüschke Christoph , Dishuck Philip C. , Lahl Katharina , Jafari Mohieddin , Aibar Sara , Zaravinos Apostolos , Steenhuizen Linda H. , Allison Lindsey R. , Gamallo Pablo , de Andres Segura Fernando , Dae Devlin Tyler , Pérez-García Vicente , Ma’ayan Avi
Published: September 2016

Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization.
FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties
Authors: Wolfe Sarah A. , Workman Emily R. , Heaney Chelcie F. , Niere Farr , Namjoshi Sanjeev , Cacheaux Luisa P. , Farris Sean P. , Drew Michael R. , Zemelman Boris V. , Harris R. Adron , Raab-Graham Kimberly F.
Published: September 2016

Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, the molecular/synaptic pathways that are shared by alcohol and antidepressants are unknown. In the current study, acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviours. To understand the functional basis of these behaviours, we examined a molecular pathway that is activated by rapid antidepressants. Ethanol, like rapid antidepressants, alters γ-aminobutyric acid type B receptor (GABABR) expression and signalling, to increase dendritic calcium. Furthermore, new GABABRs are synthesized in response to ethanol treatment, requiring fragile-X mental retardation protein (FMRP). Ethanol-dependent changes in GABABR expression, dendritic signalling, and antidepressant efficacy are absent in Fmr1-knockout (KO) mice. These findings indicate that FMRP is an important regulator of protein synthesis following alcohol exposure, providing a molecular basis for the antidepressant efficacy of acute ethanol exposure.
The tobacco-specific carcinogen-operated calcium channel promotes lung tumorigenesis via IGF2 exocytosis in lung epithelial cells
Authors: Boo Hye-Jin , Min Hye-Young , Jang Hyun-Ji , Yun Hye Jeong , Smith John Kendal , Jin Quanri , Lee Hyo-Jong , Liu Diane , Kweon Hee-Seok , Behrens Carmen , Lee J. Jack , Wistuba Ignacio I. , Lee Euni , Hong Waun Ki , Lee Ho-Young
Published: September 2016

Nicotinic acetylcholine receptors (nAChRs) binding to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces Ca2+ signalling, a mechanism that is implicated in various human cancers. In this study, we investigated the role of NNK-mediated Ca2+ signalling in lung cancer formation. We show significant overexpression of insulin-like growth factors (IGFs) in association with IGF-1R activation in human preneoplastic lung lesions in smokers. NNK induces voltage-dependent calcium channel (VDCC)-intervened calcium influx in airway epithelial cells, resulting in a rapid IGF2 secretion via the regulated pathway and thus IGF-1R activation. Silencing nAChR, α1 subunit of L-type VDCC, or various vesicular trafficking curators, including synaptotagmins and Rabs, or blockade of nAChR/VDCC-mediated Ca2+ influx significantly suppresses NNK-induced IGF2 exocytosis, transformation and tumorigenesis of lung epithelial cells. Publicly available database reveals inverse correlation between use of calcium channel blockers and lung cancer diagnosis. Our data indicate that NNK disrupts the regulated pathway of IGF2 exocytosis and promotes lung tumorigenesis.
Atomically thin quantum light-emitting diodes
Authors: Palacios-Berraquero Carmen , Barbone Matteo , Kara Dhiren M. , Chen Xiaolong , Goykhman Ilya , Yoon Duhee , Ott Anna K. , Beitner Jan , Watanabe Kenji , Taniguchi Takashi , Ferrari Andrea C. , Atatüre Mete
Published: September 2016

Transition metal dichalcogenides are optically active, layered materials promising for fast optoelectronics and on-chip photonics. We demonstrate electrically driven single-photon emission from localized sites in tungsten diselenide and tungsten disulphide. To achieve this, we fabricate a light-emitting diode structure comprising single-layer graphene, thin hexagonal boron nitride and transition metal dichalcogenide mono- and bi-layers. Photon correlation measurements are used to confirm the single-photon nature of the spectrally sharp emission. These results present the transition metal dichalcogenide family as a platform for hybrid, broadband, atomically precise quantum photonics devices.
Satellite RNAs promote pancreatic oncogenic processes via the dysfunction of YBX1
Authors: Kishikawa Takahiro , Otsuka Motoyuki , Yoshikawa Takeshi , Ohno Motoko , Ijichi Hideaki , Koike Kazuhiko
Published: September 2016

Highly repetitive tandem arrays at the centromeric and pericentromeric regions in chromosomes, previously considered silent, are actively transcribed, particularly in cancer. This aberrant expression occurs even in K-ras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are precancerous lesions. To examine the biological roles of the satellite RNAs in carcinogenesis, we construct mouse PanIN-derived cells expressing major satellite (MajSAT) RNA and show increased malignant properties. We find an increase in frequency of chromosomal instability and point mutations in both genomic and mitochondrial DNA. We identify Y-box binding protein 1 (YBX1) as a protein that binds to MajSAT RNA. MajSAT RNA inhibits the nuclear translocation of YBX1 under stress conditions, thus reducing its DNA-damage repair function. The forced expression of YBX1 significantly decreases the aberrant phenotypes. These findings indicate that during the early stage of cancer development, satellite transcripts may act as ‘intrinsic mutagens’ by inducing YBX1 dysfunction, which may be crucial in oncogenic processes.
Relative validity of a web-based food frequency questionnaire for patients with type 1 and type 2 diabetes in Denmark
Authors: Bentzen S M R , Knudsen V K , Christiensen T , Ewers B
Published: September 2016

Background:

Diet has an important role in the management of diabetes. However, little is known about dietary intake in Danish diabetes patients. A food frequency questionnaire (FFQ) focusing on most relevant nutrients in diabetes including carbohydrates, dietary fibres and simple sugars was developed and validated.

Objectives:

To examine the relative validity of nutrients calculated by a web-based food frequency questionnaire for patients with diabetes.

Design:

The FFQ was validated against a 4-day pre-coded food diary (FD). Intakes of nutrients were calculated. Means of intake were compared and cross-classifications of individuals according to intake were performed. To assess the agreement between the two methods, Pearson and Spearman’s correlation coefficients and weighted kappa coefficients were calculated.

Subjects:

Ninety patients (64 with type 1 diabetes and 26 with type 2 diabetes) accepted to participate in the study. Twenty-six were excluded from the final study population.

Setting:

64 volunteer diabetes patients at the Steno Diabetes Center.

Results:

Intakes of carbohydrates, simple sugars, dietary fibres and total energy were higher according to the FFQ compared with the FD. However, intakes of nutrients were grossly classified in the same or adjacent quartiles with an average of 82% of the selected nutrients when comparing the two methods. In general, moderate agreement between the two methods was found.

Conclusion:

The FFQ was validated for assessment of a range of nutrients. Comparing the intakes of selected nutrients (carbohydrates, dietary fibres and simple sugars), patients were classified correctly according to low and high intakes. The FFQ is a reliable dietary assessment tool to use in research and evaluation of patient education for patients with diabetes.
Eco-friendly p-type Cu2SnS3 thermoelectric material: crystal structure and transport properties
Authors: Shen Yawei , Li Chao , Huang Rong , Tian Ruoming , Ye Yang , Pan Lin , Koumoto Kunihito , Zhang Ruizhi , Wan Chunlei , Wang Yifeng
Published: September 2016

As a new eco-friendly thermoelectric material, copper tin sulfide (Cu2SnS3) ceramics were experimentally studied by Zn-doping. Excellent electrical transport properties were obtained by virtue of 3-dimensionally conductive network for holes, which are less affected by the coexistence of cubic and tetragonal phases that formed upon Zn subsitition for Sn; a highest power factors ~0.84 mW m−1 K−2 at 723 K was achieved in the 20% doped sample. Moreover, an ultralow lattice thermal conductivity close to theoretical minimum was observed in these samples, which could be related to the disordering of atoms in the coexisting cubic and tetragonal phases and the interfaces. Thanks to the phonon-glass-electron-crystal features, a maximum ZT ~ 0.58 was obtained at 723 K, which stands among the tops for sulfide thermoelectrics at the same temperature.
Tunable potential well for plasmonic trapping of metallic particles by bowtie nano-apertures
Authors: Lu Yu , Du Guangqing , Chen Feng , Yang Qing , Bian Hao , Yong Jiale , Hou Xun
Published: September 2016

In this paper, the tunable optical trapping dependence on wavelength of incident beam is theoretically investigated based on numerical simulations. The Monte Carlo method is taken into account for exploring the trapping characteristics such as average deviation and number distribution histogram of nanoparticles. It is revealed that both the width and the depth of potential well for trapping particles can be flexibly adjusted by tuning the wavelength of the incident beam. In addition, incident wavelengths for the deepest potential well and for the strongest stiffness at bottom are separated. These phenomena are explained as the strong plasmon coupling between tweezers and metallic nanoparticles. In addition, required trapping fluence and particles’ distributions show distinctive properties through carefully modifying the incident wavelengths from 1280 nm to 1300 nm. Trapping with lowest laser fluence can be realized with1280 nm laser and trapping with highest precision can be realized with 1300 nm laser. This work will provide theoretical support for advancing the manipulation of metallic particles and related applications such as single-molecule fluorescence and surface enhanced Raman spectroscopy.
A suppressor locus for MODY3-diabetes
Authors: Garcia-Gonzalez Miguel A. , Carette Claire , Bagattin Alessia , Chiral Magali , Makinistoglu Munevver Parla , Garbay Serge , Prévost Géraldine , Madaras Cécile , Hérault Yann , Leibovici Michel , Pontoglio Marco
Published: September 2016

Maturity Onset Diabetes of the Young type 3 (MODY3), linked to mutations in the transcription factor HNF1A, is the most prevalent form of monogenic diabetes mellitus. HNF1alpha-deficiency leads to defective insulin secretion via a molecular mechanism that is still not completely understood. Moreover, in MODY3 patients the severity of insulin secretion can be extremely variable even in the same kindred, indicating that modifier genes may control the onset of the disease. With the use of a mouse model for HNF1alpha-deficiency, we show here that specific genetic backgrounds (C3H and CBA) carry a powerful genetic suppressor of diabetes. A genome scan analysis led to the identification of a major suppressor locus on chromosome 3 (Moda1). Moda1 locus contains 11 genes with non-synonymous SNPs that significantly interacts with other loci on chromosomes 4, 11 and 18. Mechanistically, the absence of HNF1alpha in diabetic-prone (sensitive) strains leads to postnatal defective islets growth that is remarkably restored in resistant strains. Our findings are relevant to human genetics since Moda1 is syntenic with a human locus identified by genome wide association studies of fasting glycemia in patients. Most importantly, our results show that a single genetic locus can completely suppress diabetes in Hnf1a-deficiency.
Facile transformation of FeO/Fe3O4 core-shell nanocubes to Fe3O4 via magnetic stimulation
Authors: Lak Aidin , Niculaes Dina , Anyfantis George C. , Bertoni Giovanni , Barthel Markus J. , Marras Sergio , Cassani Marco , Nitti Simone , Athanassiou Athanassia , Giannini Cinzia , Pellegrino Teresa
Published: September 2016

Here, we propose the use of magnetic hyperthermia as a means to trigger the oxidation of Fe1−xO/Fe3−δO4 core-shell nanocubes to Fe3−δO4 phase. As a first relevant consequence, the specific absorption rate (SAR) of the initial core-shell nanocubes doubles after exposure to 25 cycles of alternating magnetic field stimulation. The improved SAR value was attributed to a gradual transformation of the Fe1−xO core to Fe3−δO4, as evidenced by structural analysis including high resolution electron microscopy and Rietveld analysis of X-ray diffraction patterns. The magnetically oxidized nanocubes, having large and coherent Fe3−δO4 domains, reveal high saturation magnetization and behave superparamagnetically at room temperature. In comparison, the treatment of the same starting core-shell nanocubes by commonly used thermal annealing process renders a transformation to γ-Fe2O3. In contrast to other thermal annealing processes, the method here presented has the advantage of promoting the oxidation at a macroscopic temperature below 37 °C. Using this soft oxidation process, we demonstrate that biotin-functionalized core-shell nanocubes can undergo a mild self-oxidation transformation without losing their functional molecular binding activity.
Simultaneous steering and imaging of magnetic particles using MRI toward delivery of therapeutics
Authors: Felfoul Ouajdi , Becker Aaron T. , Fagogenis Georgios , Dupont Pierre E.
Published: September 2016

Magnetic resonance navigation (MRN) offers the potential for real-time steering of drug particles and cells to targets throughout the body. In this technique, the magnetic gradients of an MRI scanner perform image-based steering of magnetically-labelled therapeutics through the vasculature and into tumours. A major challenge of current techniques for MRN is that they alternate between pulse sequences for particle imaging and propulsion. Since no propulsion occurs while imaging the particles, this results in a significant reduction in imaging frequency and propulsive force. We report a new approach in which an imaging sequence is designed to simultaneously image and propel particles. This sequence provides a tradeoff between maximum propulsive force and imaging frequency. In our reported example, the sequence can image at 27 Hz while still generating 95% of the force produced by a purely propulsive pulse sequence. We implemented our pulse sequence on a standard clinical scanner using millimetre-scale particles and demonstrated high-speed (74 mm/s) navigation of a multi-branched vascular network phantom. Our study suggests that the magnetic gradient magnitudes previously demonstrated to be sufficient for pure propulsion of micron-scale therapeutics in magnetic resonance targeting (MRT) could also be sufficient for real-time steering of these particles.
Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex
Authors: Postila Pekka A. , Kaszuba Karol , Kuleta Patryk , Vattulainen Ilpo , Sarewicz Marcin , Osyczka Artur , Róg Tomasz
Published: September 2016

The cytochrome (cyt) bc1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme’s substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Qi-site of the cyt bc1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Qi-site to facilitate binding of half-protonated semiquinone – a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Qi-site.
Sporicidal performance induced by photocatalytic production of organic peroxide under visible light irradiation
Authors: Yamaguchi Yuichi , Shimodo Takahito , Chikamori Noriyasu , Usuki Sho , Kanai Yoshihiro , Endo Takeshi , Katsumata Ken-ichi , Terashima Chiaki , Ikekita Masahiko , Fujishima Akira , Suzuki Tomonori , Sakai Hideki , Nakata Kazuya
Published: September 2016

Bacteria that cause serious food poisoning are known to sporulate under conditions of nutrient and water shortage. The resulting spores have much greater resistance to common sterilization methods, such as heating at 100 °C and exposure to various chemical agents. Because such bacteria cannot be inactivated with typical alcohol disinfectants, peroxyacetic acid (PAA) often is used, but PAA is a harmful agent that can seriously damage human health. Furthermore, concentrated hydrogen peroxide, which is also dangerous, must be used to prepare PAA. Thus, the development of a facile and safe sporicidal disinfectant is strongly required. In this study, we have developed an innovative sporicidal disinfection method that employs the combination of an aqueous ethanol solution, visible light irradiation and a photocatalyst. We successfully produced a sporicidal disinfectant one hundred times as effective as commercially available PAA, while also resolving the hazards and odor problems associated with PAA. The method presented here can potentially be used as a replacement for the general disinfectants employed in the food and health industries.
Correction: Corrigendum: The Expression of Human Cytomegalovirus MicroRNA MiR-UL148D during Latent Infection in Primary Myeloid Cells Inhibits Activin A-triggered Secretion of IL-6
Authors: Lau Betty , Poole Emma , Krishna Benjamin , Montanuy Immaculada , Wills Mark R. , Murphy Eain , Sinclair John
Published: September 2016

Scientific Reports 6: Article number: 31205; published online: 05 August 2016; updated: 26 September 2016. The original version of this Article contained an error in the spelling of the author Immaculada Montanuy which was incorrectly given as Immaculada Sellart. In addition, the Author Contributions Statement contained errors.
Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors
Authors: Kanazaki Kengo , Sano Kohei , Makino Akira , Homma Tsutomu , Ono Masahiro , Saji Hideo
Published: September 2016

Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging.
Exploring functional roles of TRPV1 intracellular domains with unstructured peptide-insertion screening
Authors: Ma Linlin , Yang Fan , Vu Simon , Zheng Jie
Published: September 2016

TRPV1 is a polymodal nociceptor for diverse physical and chemical stimuli that interact with different parts of the channel protein. Recent cryo-EM studies revealed detailed channel structures, opening the door for mapping structural elements mediating activation by each stimulus. Towards this goal, here we have combined unstructured peptide-insertion screening (UPS) with electrophysiological and fluorescence recordings to explore structural and functional roles of the intracellular regions of TRPV1 in mediating various activation stimuli. We found that most of the tightly packed protein regions did not tolerate structural perturbation by UPS when tested, indicating that structural integrity of the intracellular region is critical. In agreement with previous reports, Ca2+-dependent desensitization is strongly dependent on both intracellular N- and C-terminal domains; insertions of an unstructured peptide between these domains and the transmembrane core domain nearly eliminated Ca2+-dependent desensitization. In contrast, channel activations by capsaicin, low pH, divalent cations, and even heat are mostly intact in mutant channels containing the same insertions. These observations suggest that the transmembrane core domain of TRPV1, but not the intracellular domains, is responsible for sensing these stimuli.
Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma
Authors: Zhang Yi-Fan , Ho Mitchell
Published: September 2016

Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework. Interestingly, we found that the proline at position 41, a non-CDR residue in heavy chain variable regions (VH), is important for humanization of mouse antibodies. We also showed that two humanized anti-GPC3 antibodies (hYP7 and hYP9.1b) in the IgG format induced antibody-dependent cell-mediated cytotoxicity and complement-dependent-cytotoxicity in GPC3-positive cancer cells. The hYP7 antibody was tested and showed inhibition of HCC xenograft tumor growth in nude mice. This study successfully humanizes and validates high affinity anti-GPC3 antibodies and sets a foundation for future development of these antibodies in various clinical formats in the treatment of liver cancer.