bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing oral proficiency with VoiceThread: Learners’ strategic uses and views
Authors: Dugartsyrenova Vera A. , Sardegna Veronica G.
Published: September 2016

This study explored Russian as a foreign language (RFL) learners’ self-reported strategic uses ofVoiceThread(VT)—a multimodal asynchronous computer-mediated communication tool—in order to gain insights into learner perceived effectiveness of VT for second language (L2) oral skills development and to determine the factors that contributed to those perceptions. The participants were eight undergraduate students who attended six weekly tutoring sessions that combined face-to-face (F2F) RFL instruction with VT activities. VT allowed them to access text-based, graphic, video, and aural linguistic input; record and store audio/video-recorded output; listen and comment on peers’ recordings; and receive individualized teacher feedback on oral performance. Data from activity logs and researcher field notes were triangulated with participants’ responses to two surveys and a semi-structured oral interview. Findings indicated that participants believed that VT supported their oral proficiency development through the provision of additional time and resources for independent planning, rehearsal, and controlled production of L2 forms. Most participants also agreed that VT’s playback and record features were the most beneficial for developing language skills, enhancing the reflection process, and facilitating self-assessment and creativity in the L2. Yet, despite VT’s multimodal affordances and the availability of communicative tasks via VT, participants did not perceive VT as a social environment that could promote peer-to-peer interaction or replace F2F communication. A thematic data analysis suggested that participants’ preferences for language learning tasks influenced their strategic uses of VT’s features, which ultimately affected their perceptions of VT’s value for promoting meaningful language learning interactions. Pedagogical considerations are discussed.
Treatment of mixed features in bipolar disorder
Authors: Rosenblat Joshua D. , McIntyre Roger S.
Published: September 2016

Mood episodes with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)–defined mixed features are highly prevalent in bipolar disorder (BD), affecting ~40% of patients during the course of illness. Mixed states are associated with poorer clinical outcomes, greater treatment resistance, higher rates of comorbidity, more frequent mood episodes, and increased rates of suicide. The objectives of the current review are to identify, summarize, and synthesize studies assessing the efficacy of treatments specifically for BD I and II mood episodes (ie, including manic, hypomanic, and major depressive episodes) with DSM-5–defined mixed features. Two randomized controlled trials (RCTs) and 6 post-hoc analyses were identified, all of which assessed the efficacy of second-generation antipsychotics (SGAs) for the acute treatment of BD mood episodes with mixed features. Results from these studies provide preliminary support for SGAs as efficacious treatments for both mania with mixed features and bipolar depression with mixed features. However, there are inadequate data to definitively support or refute the clinical use of specific agents. Conventional mood stabilizing agents (eg, lithium and divalproex) have yet to have been adequately studied in DSM-5–defined mixed features. Further study is required to assess the efficacy, safety, and tolerability of treatments specifically for BD mood episodes with mixed features.
The return of the chatbots
Authors: DALE ROBERT
Published: September 2016

By all accounts, 2016 is the year of the chatbot. Some commentators take the view that chatbot technology will be so disruptive that it will eliminate the need for websites and apps. But chatbots have a long history. So what's new, and what's different this time? And is there an opportunity here to improve how our industry does technology transfer?
CVLT-II Forced Choice Recognition Trial as an Embedded Validity Indicator: A Systematic Review of the Evidence
Authors: Schwartz Eben S. , Erdodi Laszlo , Rodriguez Nicholas , Ghosh Jyotsna J. , Curtain Joshua R. , Flashman Laura A. , Roth Robert M.
Published: September 2016

Objectives: The Forced Choice Recognition (FCR) trial of the California Verbal Learning Test, 2nd edition, was designed as an embedded performance validity test (PVT). To our knowledge, this is the first systematic review of classification accuracy against reference PVTs. Methods: Results from peer-reviewed studies with FCR data published since 2002 encompassing a variety of clinical, research, and forensic samples were summarized, including 37 studies with FCR failure rates (N=7575) and 17 with concordance rates with established PVTs (N=4432). Results: All healthy controls scored >14 on FCR. On average, 16.9% of the entire sample scored ≤14, while 25.9% failed reference PVTs. Presence or absence of external incentives to appear impaired (as identified by researchers) resulted in different failure rates (13.6% vs. 3.5%), as did failing or passing reference PVTs (49.0% vs. 6.4%). FCR ≤14 produced an overall classification accuracy of 72%, demonstrating higher specificity (.93) than sensitivity (.50) to invalid performance. Failure rates increased with the severity of cognitive impairment. Conclusions: In the absence of serious neurocognitive disorder, FCR ≤14 is highly specific, but only moderately sensitive to invalid responding. Passing FCR does not rule out a non-credible presentation, but failing FCR rules it in with high accuracy. The heterogeneity in sample characteristics and reference PVTs, as well as the quality of the criterion measure across studies, is a major limitation of this review and the basic methodology of PVT research in general. (JINS, 2016, 22, 851–858)
The Last Campaign and Death of Jebe Noyan
Authors: POW STEPHEN
Published: September 2016

Despite Jebe Noyan's importance to the expansion of Chinggis Khan's empire, the Mongol general remains a shadowy figure. In part this stems from the absence of any biography of Jebe in the Yuan Shi and much uncertainly surrounds when, and in what circumstances, he died. Here the argument is made that the Novgorod First Chronicle provides a description of Jebe's capture and death at the hands of the Kipchaks during the 1223 campaign which culminated with the decisive Battle of the Kalka River. The silence and ambiguity surrounding Jebe's fate in pro-Mongol sources of the thirteenth century can perhaps be explained by a taboo surrounding the disgraceful circumstances of his capture and execution.

The paper explores the implications which this identification holds for how we assess the westward campaign of Jebe and Sübe'etei (1220-1224), often perceived as a reconnaissance mission, and how the Mongol leadership viewed enemies west of the Volga in its aftermath. This, in turn, sheds light on the preparations the Mongols made for their return in force to the region in the 1230s. Finally a theory is offered for why Jebe's identification was not made previously which illustrates the challenges facing researchers of the Mongol Empire.
Polarization Second Harmonic Generation Discriminates Between Fresh and Aged Starch-Based Adhesives Used in Cultural Heritage
Authors: Psilodimitrakopoulos Sotiris , Gavgiotaki Evaggelia , Melessanaki Kristallia , Tsafas Vassilis , Filippidis George
Published: September 2016

In this work, we report that polarization second harmonic generation (PSHG) microscopy, commonly used in biomedical imaging, can quantitatively discriminate naturally aged from fresh starch-based glues used for conservation or restoration of paintings, works of art on paper, and books. Several samples of fresh and aged (7 years) flour and starch pastes were investigated by use of PSHG. In these types of adhesives, widely used in cultural heritage conservation, second harmonic generation (SHG) contrast originates primarily from the starch granules. It was found that in aged glues, the starch SHG effective orientation (SHG angle, θ) shifts to significantly higher values in comparison to the fresh granules. This shift is attributed to the different degree of granule hydration between fresh and aged adhesives. Thus noninvasive high-resolution nonlinear scattering can be employed to detect and quantify the degree of deterioration of restoration adhesives and to provide guidance toward future conservation treatments.
On the Chemical Signature and Origin of Dicoppertrihydroxyformate (Cu2(OH)3HCOO) Formed on Copper Miniatures of 17th and 18th centuries
Authors: Veiga Alfredina , Teixeira Dora Martins , Candeias António J. , Mirão José , Rodrigues Paulo Simões , Teixeira Jorge Ginja
Published: September 2016

A corrosion product rarely reported in the literature has been found on the copper support of three miniature paintings of the 17th and 18th centuries. This product, which has been identified as dicoppertrihydroxyformate (Cu2(OH)3HCOO), is an unusual basic copper formate found on copper artifacts. The identification and characterization of dicoppertrihydroxyformate was carried out directly over the corroded surface of the objects, using a nondestructive approach, which combines the integrated use of various microanalytical techniques. Using this approach, it was possible to obtain a set of new reference data about the natural form of Cu2(OH)3HCOO, that will enable its unambiguous identification in other similar objects. In this work, the probable causes that may have contributed to its formation are also discussed.
Removing Beam Current Artifacts in Helium Ion Microscopy: A Comparison of Image Processing Techniques
Authors: Barlow Anders J. , Portoles Jose F. , Sano Naoko , Cumpson Peter J.
Published: September 2016

The development of the helium ion microscope (HIM) enables the imaging of both hard, inorganic materials and soft, organic or biological materials. Advantages include outstanding topographical contrast, superior resolution down to <0.5 nm at high magnification, high depth of field, and no need for conductive coatings. The instrument relies on helium atom adsorption and ionization at a cryogenically cooled tip that is atomically sharp. Under ideal conditions this arrangement provides a beam of ions that is stable for days to weeks, with beam currents in the order of picoamperes. Over time, however, this stability is lost as gaseous contamination builds up in the source region, leading to adsorbed atoms of species other than helium, which ultimately results in beam current fluctuations. This manifests itself as horizontal stripe artifacts in HIM images. We investigate post-processing methods to remove these artifacts from HIM images, such as median filtering, Gaussian blurring, fast Fourier transforms, and principal component analysis. We arrive at a simple method for completely removing beam current fluctuation effects from HIM images while maintaining the full integrity of the information within the image.
Telematic driving profile classification in car insurance pricing
Authors: Weidner Wiltrud , Transchel Fabian W.G. , Weidner Robert
Published: September 2016

This paper presents pricing innovations to German car insurance. The purpose is to provide an effective approach to adapting actuarial pricing decision to incorporate telematic data, which differs substantially from established tariff criteria in complexity and volume. A vehicle mobility model and a real-world sample of driving profiles form the input into the analysis. We propose an allocation of the driving profiles based on velocity and acceleration parameters to specific driving styles for evaluating the driving behaviour to subsequently enable discounts or surcharges on the premiums to obtain usage-based insurance premiums. The result is highly relevant for actuaries, who calculate the tariffs, but also for managers, as they have to make a pricing decision.
Emotional Intelligence Training in Team Sports
Authors: Campo Mickaël , Laborde Sylvain , Mosley Emma
Published: September 2016

Abstract. The aim of this study was to test the effectiveness of an emotional intelligence (EI) training intervention to improve EI at trait level. Sixty-seven rugby players participated in the study. One group received a specific EI training intervention, while the other group served as a control group. The intervention consisted of four face-to-face sessions over a 5-month period, with homework and follow-up procedures. Results showed that the EI training was partially successful in increasing EI, and demonstrates it is possible to enhance EI at trait level in participants while they may not have preexisting motivation to do so.
A dynamic code for economic object valuation in prefrontal cortex neurons
Authors: Tsutsui Ken-Ichiro , Grabenhorst Fabian , Kobayashi Shunsuke , Schultz Wolfram
Published: September 2016

Neuronal reward valuations provide the physiological basis for economic behaviour. Yet, how such valuations are converted to economic decisions remains unclear. Here we show that the dorsolateral prefrontal cortex (DLPFC) implements a flexible value code based on object-specific valuations by single neurons. As monkeys perform a reward-based foraging task, individual DLPFC neurons signal the value of specific choice objects derived from recent experience. These neuronal object values satisfy principles of competitive choice mechanisms, track performance fluctuations and follow predictions of a classical behavioural model (Herrnstein’s matching law). Individual neurons dynamically encode both, the updating of object values from recently experienced rewards, and their subsequent conversion to object choices during decision-making. Decoding from unselected populations enables a read-out of motivational and decision variables not emphasized by individual neurons. These findings suggest a dynamic single-neuron and population value code in DLPFC that advances from reward experiences to economic object values and future choices.
Erratum: A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
Authors: Rivas Manuel A. , Graham Daniel , Sulem Patrick , Stevens Christine , Desch A. Nicole , Goyette Philippe , Gudbjartsson Daniel , Jonsdottir Ingileif , Thorsteinsdottir Unnur , Degenhardt Frauke , Mucha Sören , Kurki Mitja I. , Li Dalin , D’Amato Mauro , Annese Vito , Vermeire Severine , Weersma Rinse K. , Halfvarson Jonas , Paavola-Sakki Paulina , Lappalainen Maarit , Lek Monkol , Cummings Beryl , Tukiainen Taru , Haritunians Talin , Halme Leena , Koskinen Lotta L. E. , Ananthakrishnan Ashwin N. , Luo Yang , Heap Graham A. , Visschedijk Marijn C. ,   UK IBD Genetics Consortium, Barrett J. , de Lange K. , Edwards C. , Hart A. , Hawkey C. , Jostins L. , Kennedy N. , Lamb C. , Lee J. , Lees C. , Mansfield J. , Mathew C. , Mowatt C. , Newman W. , Nimmo E. , Parkes M. , Pollard M. , Prescott N. , Randall J. , Rice D. , Satsangi J. , Simmons A. , Tremelling M. , Uhlig H. , Wilson D. ,   NIDDK IBD Genetics Consortium, Abraham C. , Achkar J.P. , Bitton A. , Boucher G. , Croitoru K. , Fleshner P. , Glas J. , Kugathasan S. , Limbergen J. V. , Milgrom R. , Proctor D. , Regueiro M. , Schumm P. L. , Sharma Y. , Stempak J. M. , Targan S. R. , Wang M. H. , MacArthur Daniel G. , Neale Benjamin M. , Ahmad Tariq , Anderson Carl A. , Brant Steven R. , Duerr Richard H. , Silverberg Mark S. , Cho Judy H. , Palotie Aarno , Saavalainen Päivi , Kontula Kimmo , Färkkilä Martti , McGovern Dermot P. B. , Franke Andre , Stefansson Kari , Rioux John D. , Xavier Ramnik J. , Daly Mark J.
Published: September 2016

Nature Communications 7 Article number: 12342 (2016); Published 9 August 2016; Updated 13 September 2016 The HTML version of this Article incorrectly listed the authors of the UK IBD Genetics Consortium and the NIDDK IBD Genetics Consortium individually in the main author list. This has now been corrected in the HTML; the PDF version of the paper was correct from the time of publication.
Erratum: Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth
Authors: Gerling Marco , Büller Nikè V.J.A. , Kirn Leonard M , Joost Simon , Frings Oliver , Englert Benjamin , Bergström Åsa , Kuiper Raoul V. , Blaas Leander , Wielenga Mattheus C. B. , Almer Sven , Kühl Anja A. , Fredlund Erik , van den Brink Gijs R. , Toftgård Rune
Published: September 2016

Nature Communications 7:12321 doi: (2016); Published 5 Aug 2016; Updated 13 Sep 2016 In Fig. 6f of this Article, the labelling of the two immunohistochemistry images was inadvertently changed from ‘Haematoxylin, ki67’ to ‘Haematoxylin, Casp-3’ during the production process. The correct version of Fig.
Dispersion of nonresonant third-order nonlinearities in GeSiSn ternary alloys
Authors: De Leonardis Francesco , Troia Benedetto , Soref Richard A. , Passaro Vittorio M. N.
Published: September 2016

Silicon (Si), tin (Sn), and germanium (Ge) alloys have attracted research attention as direct band gap semiconductors with applications in electronics and optoelectronics. In particular, GeSn field effect transistors can exhibit very high performance in terms of power reduction and operating speed because of the high electron drift mobility, while the SiGeSn system can be constructed using CMOS-compatible techniques to realize lasers, LED, and photodetectors. The wide Si, Ge and Sn transparencies allow the use of binary and ternary alloys extended to mid-IR wavelengths, where nonlinearities can also be employed. However, neither theoretical or experimental predictions of nonlinear features in SiGeSn alloys are reported in the literature. For the first time, a rigorous and detailed physical investigation is presented to estimate the two photon absorption (TPA) coefficient and the Kerr refractive index for the SiGeSn alloy up to 12 μm. The TPA spectrum, the effective TPA wavelength cut-off, and the Kerr nonlinear refractive index have been determined as a function of alloy compositions. The promising results achieved can pave the way to the demonstration of on-chip nonlinear-based applications, including mid-IR spectrometer-on-a-chip, all-optical wavelength down/up-conversion, frequency comb generation, quantum-correlated photon-pair source generation and supercontinuum source creation, as well as Raman lasing.
Thermomechanical controls on magma supply and volcanic deformation: application to Aira caldera, Japan
Authors: Hickey James , Gottsmann Joachim , Nakamichi Haruhisa , Iguchi Masato
Published: September 2016

Ground deformation often precedes volcanic eruptions, and results from complex interactions between source processes and the thermomechanical behaviour of surrounding rocks. Previous models aiming to constrain source processes were unable to include realistic mechanical and thermal rock properties, and the role of thermomechanical heterogeneity in magma accumulation was unclear. Here we show how spatio-temporal deformation and magma reservoir evolution are fundamentally controlled by three-dimensional thermomechanical heterogeneity. Using the example of continued inflation at Aira caldera, Japan, we demonstrate that magma is accumulating faster than it can be erupted, and the current uplift is approaching the level inferred prior to the violent 1914 Plinian eruption. Magma storage conditions coincide with estimates for the caldera-forming reservoir ~29,000 years ago, and the inferred magma supply rate indicates a ~130-year timeframe to amass enough magma to feed a future 1914-sized eruption. These new inferences are important for eruption forecasting and risk mitigation, and have significant implications for the interpretations of volcanic deformation worldwide.
Lipid membrane-mediated attraction between curvature inducing objects
Authors: van der Wel Casper , Vahid Afshin , Šarić Anđela , Idema Timon , Heinrich Doris , Kraft Daniela J.
Published: September 2016

The interplay of membrane proteins is vital for many biological processes, such as cellular transport, cell division, and signal transduction between nerve cells. Theoretical considerations have led to the idea that the membrane itself mediates protein self-organization in these processes through minimization of membrane curvature energy. Here, we present a combined experimental and numerical study in which we quantify these interactions directly for the first time. In our experimental model system we control the deformation of a lipid membrane by adhering colloidal particles. Using confocal microscopy, we establish that these membrane deformations cause an attractive interaction force leading to reversible binding. The attraction extends over 2.5 times the particle diameter and has a strength of three times the thermal energy (−3.3 kBT). Coarse-grained Monte-Carlo simulations of the system are in excellent agreement with the experimental results and prove that the measured interaction is independent of length scale. Our combined experimental and numerical results reveal membrane curvature as a common physical origin for interactions between any membrane-deforming objects, from nanometre-sized proteins to micrometre-sized particles.
Deoxyinosine triphosphate induces MLH1/PMS2- and p53-dependent cell growth arrest and DNA instability in mammalian cells
Authors: Yoneshima Yasuto , Abolhassani Nona , Iyama Teruaki , Sakumi Kunihiko , Shiomi Naoko , Mori Masahiko , Shiomi Tadahiro , Noda Tetsuo , Tsuchimoto Daisuke , Nakabeppu Yusaku
Published: September 2016

Deoxyinosine (dI) occurs in DNA either by oxidative deamination of a previously incorporated deoxyadenosine residue or by misincorporation of deoxyinosine triphosphate (dITP) from the nucleotide pool during replication. To exclude dITP from the pool, mammals possess specific hydrolysing enzymes, such as inosine triphosphatase (ITPA). Previous studies have shown that deficiency in ITPA results in cell growth suppression and DNA instability. To explore the mechanisms of these phenotypes, we analysed ITPA-deficient human and mouse cells. We found that both growth suppression and accumulation of single-strand breaks in nuclear DNA of ITPA-deficient cells depended on MLH1/PMS2. The cell growth suppression of ITPA-deficient cells also depended on p53, but not on MPG, ENDOV or MSH2. ITPA deficiency significantly increased the levels of p53 protein and p21 mRNA/protein, a well-known target of p53, in an MLH1-dependent manner. Furthermore, MLH1 may also contribute to cell growth arrest by increasing the basal level of p53 activity.
A change in coral extension rates and stable isotopes after El Niño-induced coral bleaching and regional stress events
Authors: Hetzinger S. , Pfeiffer M. , Dullo W.-Chr. , Zinke J. , Garbe-Schönberg D.
Published: September 2016

Coral reefs are biologically diverse ecosystems threatened with effective collapse under rapid climate change, in particular by recent increases in ocean temperatures. Coral bleaching has occurred during major El Niño warming events, at times leading to the die-off of entire coral reefs. Here we present records of stable isotopic composition, Sr/Ca ratios and extension rate (1940–2004) in coral aragonite from a northern Venezuelan site, where reefs were strongly impacted by bleaching following the 1997–98 El Niño. We assess the impact of past warming events on coral extension rates and geochemical proxies. A marked decrease in coral (Pseudodiploria strigosa) extension rates coincides with a baseline shift to more negative values in oxygen and carbon isotopic composition after 1997–98, while a neighboring coral (Siderastrea siderea) recovered to pre-bleaching extension rates simultaneously. However, other stressors, besides high temperature, might also have influenced coral physiology and geochemistry. Coastal Venezuelan reefs were exposed to a series of extreme environmental fluctuations since the mid-1990s, i.e. upwelling, extreme rainfall and sediment input from landslides. This work provides important new data on the potential impacts of multiple regional stress events on coral isotopic compositions and raises questions about the long-term influence on coral-based paleoclimate reconstructions.
Vitamin D treatment attenuates 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis
Authors: Liu Tianjing , Shi Yongyan , Du Jie , Ge Xin , Teng Xu , Liu Lu , Wang Enbo , Zhao Qun
Published: September 2016

Crohn’s disease (CD) and ulcerative colitis (UC) have different immunological mechanisms, while both of them are potential targets of vitamin D treatment. In this study, we have tried to address the role of vitamin D in CD and UC using two mouse models. Mice of C57B6L were given vitamin D before the induction of colitis. Our results showed that vitamin D attenuated 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis. Vitamin D could preserve the local histology, alleviate inflammation, suppress apoptosis, maintain tight junction function and decrease permeability. Interestingly, it has more of an effect on local structure preservation and inflammation inhibition in CD than in UC mice. Vitamin D blocked the increase of helper T-cell type 1 (Th1)- and helper T-cell type 17 (Th17)-related cytokines in TNBS-induced colitis. But the increase of helper T-cell type 2 (Th2)- and regulatory T cells (Treg)-related cytokines was augmented at the same time in oxazolone-induced colitis which counteracted each other. Our study helps elucidate the differential protective effects of vitamin D on CD and UC patients, as reported in literature.
An Auditory BCI System for Assisting CRS-R Behavioral Assessment in Patients with Disorders of Consciousness
Authors: Xiao Jun , Xie Qiuyou , He Yanbin , Yu Tianyou , Lu Shenglin , Huang Ningmeng , Yu Ronghao , Li Yuanqing
Published: September 2016

The Coma Recovery Scale-Revised (CRS-R) is a consistent and sensitive behavioral assessment standard for disorders of consciousness (DOC) patients. However, the CRS-R has limitations due to its dependence on behavioral markers, which has led to a high rate of misdiagnosis. Brain-computer interfaces (BCIs), which directly detect brain activities without any behavioral expression, can be used to evaluate a patient’s state. In this study, we explored the application of BCIs in assisting CRS-R assessments of DOC patients. Specifically, an auditory passive EEG-based BCI system with an oddball paradigm was proposed to facilitate the evaluation of one item of the auditory function scale in the CRS-R – the auditory startle. The results obtained from five healthy subjects validated the efficacy of the BCI system. Nineteen DOC patients participated in the CRS-R and BCI assessments, of which three patients exhibited no responses in the CRS-R assessment but were responsive to auditory startle in the BCI assessment. These results revealed that a proportion of DOC patients who have no behavioral responses in the CRS-R assessment can generate neural responses, which can be detected by our BCI system. Therefore, the proposed BCI may provide more sensitive results than the CRS-R and thus assist CRS-R behavioral assessments.
4-Hydroxy-2-nonenal induces apoptosis by activating ERK1/2 signaling and depleting intracellular glutathione in intestinal epithelial cells
Authors: Ji Yun , Dai Zhaolai , Wu Guoyao , Wu Zhenlong
Published: September 2016

Excessive reactive oxygen species (ROS) induces oxidative damage to cellular constituents, ultimately leading to induction of apoptotic cell death and the pathogenesis of various diseases. The molecular mechanisms for the action of ROS in intestinal diseases remain poorly defined. Here, we reported that 4-hydroxy-2-nonenal (4-HNE) treatment led to capses-3-dependent apoptosis accompanied by increased intracellular ROS level and reduced glutathione concentration in intestinal epithelial cells. These effects of 4-HNE were markedly abolished by the antioxidant L-cysteine derivative N-acetylcysteine (NAC). Further studies demonstrated that the protective effect of NAC was associated with restoration of intracellular redox state by Nrf2-related regulation of expression of genes involved in intracellular glutathione (GSH) biosynthesis and inactivation of 4-HNE-induced phosphorylation of extracellular signal-regulated protein kinases (ERK1/2). The 4-HNE-induced ERK1/2 activation was mediated by repressing mitogen-activated protein kinase phosphatase-1 (MKP-1), a negative regulator of ERK1/2, through a proteasome-dependent degradation mechanism. Importantly, either overexpression of MKP-1 or NAC treatment blocked 4-HNE-induced MKP-1 degradation, thereby protecting cell from apoptosis. These novel findings provide new insights into a functional role of MKP-1 in oxidative stress-induced cell death by regulating ERK1/2 MAP kinase in intestinal epithelial cells.
Two-dimensional artificial light-harvesting antennae with predesigned high-order structure and robust photosensitising activity
Authors: Feng Xiao , Ding Xuesong , Chen Long , Wu Yang , Liu Lili , Addicoat Matthew , Irle Stephan , Dong Yuping , Jiang Donglin
Published: September 2016

Highly ordered discrete assemblies of chlorophylls that are found in natural light-harvesting antennae are key to photosynthesis, which converts light energy to chemical energy and is the principal producer of organic matter on Earth. Porphyrins and phthalocyanines, which are analogues of chlorophylls, exhibit a strong absorbance of visible and near-infrared light, respectively. A highly ordered porphyrin-co-phthalocyanine antennae would harvest photons over the entire solar spectrum for chemical transformation. However, such a robust antennae has not yet been synthesised. Herein, we report a strategy that merges covalent bonds and noncovalent forces to produce highly ordered two-dimensional porphyrin-co-phthalocyanine antennae. This methodology enables control over the stoichiometry and order of the porphyrin and phthalocyanine units; more importantly, this approach is compatible with various metalloporphyrin and metallophthalocyanine derivatives and thus may lead to the generation of a broad structural diversity of two-dimensional artificial antennae. These ordered porphyrin-co-phthalocyanine two-dimensional antennae exhibit unique optical properties and catalytic functions that are not available with single-component or non-structured materials. These 2D artificial antennae exhibit exceptional light-harvesting capacity over the entire solar spectrum as a result of a synergistic light-absorption effect. In addition, they exhibit outstanding photosensitising activities in using both visible and near-infrared photons for producing singlet oxygen.
Crocetin exploits p53-induced death domain (PIDD) and FAS-associated death domain (FADD) proteins to induce apoptosis in colorectal cancer
Authors: Ray Pallab , Guha Deblina , Chakraborty Juni , Banerjee Shuvomoy , Adhikary Arghya , Chakraborty Samik , Das Tanya , Sa Gaurisankar
Published: September 2016

Tumor suppressor p53 preserves the genomic integrity by restricting anomaly at the gene level. The hotspots for mutation in half of all colon cancers reside in p53. Hence, in a p53-mutated cellular milieu targeting cancer cells may be achievable by targeting the paralogue(s) of p53. Here we have shown the effectiveness of crocetin, a dietary component, in inducing apoptosis of colon cancer cells with varying p53 status. In wild-type p53-expressing cancer cells, p53 in one hand transactivates BAX and in parallel up-regulates p53-induced death domain protein (PIDD) that in turn cleaves and activates BID through caspase-2. Both BAX and t-BID converge at mitochondria to alter the transmembrane potential thereby leading to caspase-9 and caspase-3-mediated apoptosis. In contrast, in functional p53-impaired cells, this phytochemical exploits p53-paralogue p73, which up-regulates FAS to cleave BID through FAS-FADD-caspase-8-pathway. These findings not only underline the phenomenon of functional switch-over from p53 to p73 in p53-impaired condition, but also validate p73 as a promising and potential target for cancer therapy in absence of functional p53.
The porin VDAC2 is the mitochondrial platform for Bax retrotranslocation
Authors: Lauterwasser Joachim , Todt Franziska , Zerbes Ralf M. , Nguyen Thanh Ngoc , Craigen William , Lazarou Michael , van der Laan Martin , Edlich Frank
Published: September 2016

The pro-apoptotic Bcl-2 protein Bax can permeabilize the outer mitochondrial membrane and therefore commit human cells to apoptosis. Bax is regulated by constant translocation to the mitochondria and retrotranslocation back into the cytosol. Bax retrotranslocation depends on pro-survival Bcl-2 proteins and stabilizes inactive Bax. Here we show that Bax retrotranslocation shuttles membrane-associated and membrane-integral Bax from isolated mitochondria. We further discover the mitochondrial porin voltage-dependent anion channel 2 (VDAC2) as essential component and platform for Bax retrotranslocation. VDAC2 ensures mitochondria-specific membrane association of Bax and in the absence of VDAC2 Bax localizes towards other cell compartments. Bax retrotranslocation is also regulated by nucleotides and calcium ions, suggesting a potential role of the transport of these ions through VDAC2 in Bax retrotranslocation. Together, our results reveal the unanticipated bifunctional role of VDAC2 to target Bax specifically to the mitochondria and ensure Bax inhibition by retrotranslocation into the cytosol.
Decoupling the refractive index from the electrical properties of transparent conducting oxides via periodic superlattices
Authors: Caffrey David , Norton Emma , Coileáin Cormac Ó , Smith Christopher M. , Bulfin Brendan , Farrell Leo , Shvets Igor V. , Fleischer Karsten
Published: September 2016

We demonstrate an alternative approach to tuning the refractive index of materials. Current methodologies for tuning the refractive index of a material often result in undesirable changes to the structural or optoelectronic properties. By artificially layering a transparent conducting oxide with a lower refractive index material the overall film retains a desirable conductivity and mobility while acting optically as an effective medium with a modified refractive index. Calculations indicate that, with our refractive index change of 0.2, a significant reduction of reflective losses could be obtained by the utilisation of these structures in optoelectronic devices. Beyond this, periodic superlattice structures present a solution to decouple physical properties where the underlying electronic interaction is governed by different length scales.
EGFP oligomers as natural fluorescence and hydrodynamic standards
Authors: Vámosi György , Mücke Norbert , Müller Gabriele , Krieger Jan Wolfgang , Curth Ute , Langowski Jörg , Tóth Katalin
Published: September 2016

EGFP oligomers are convenient standards for experiments on fluorescent protein-tagged biomolecules. In this study, we characterized their hydrodynamic and fluorescence properties. Diffusion coefficients D of EGFP1–4 were determined by analytical ultracentrifugation with fluorescence detection and by fluorescence correlation spectroscopy (FCS), yielding 83.4…48.2 μm2/s and 97.3…54.8 μm2/s from monomer to tetramer. A “barrels standing in a row” model agreed best with the sedimentation data. Oligomerization red-shifted EGFP emission spectra without any shift in absorption. Fluorescence anisotropy decreased, indicating homoFRET between the subunits. Fluorescence lifetime decreased only slightly (4%) indicating insignificant quenching by FRET to subunits in non-emitting states. FCS-measured D, particle number and molecular brightness depended on dark states and light-induced processes in distinct subunits, resulting in a dependence on illumination power different for monomers and oligomers. Since subunits may be in “on” (bright) or “off” (dark) states, FCS-determined apparent brightness is not proportional to that of the monomer. From its dependence on the number of subunits, the probability of the “on” state for a subunit was determined to be 96% at pH 8 and 77% at pH 6.38, i.e., protonation increases the dark state. These fluorescence properties of EGFP oligomeric standards can assist interpreting results from oligomerized EGFP fusion proteins of biological interest.
Protease-activated receptor-1 deficiency protects against streptozotocin-induced diabetic nephropathy in mice
Authors: Waasdorp Maaike , Duitman JanWillem , Florquin Sandrine , Spek C. Arnold
Published: September 2016

Endogenously administered activated protein C ameliorates diabetic nephropathy (DN) in a protease-activated receptor-1 (PAR-1)-dependent manner, suggesting that PAR-1 activation limits the progression of DN. Activation of PAR-1 in fibroblast-like cells, however, induces proliferation and extracellular matrix production, thereby driving fibrotic disease. Considering the key role of mesangial proliferation and extracellular matrix production during DN, PAR-1 may in fact potentiate diabetes-induced kidney injury. To determine the net effect of PAR-1 in DN, streptozotocin-induced DN was studied in wild type and PAR-1 deficient mice. Subsequent mechanistic insight was obtained by assessing profibrotic responses of mesangial and tubular epithelial cells in vitro, following PAR-1 stimulation and inhibition. Despite having similar glucose levels, PAR-1 deficient mice developed less kidney damage after induction of diabetes, as evidenced by diminished proteinuria, plasma cystatin C levels, expansion of the mesangial area, and tubular atrophy. In vitro, PAR-1 signaling in mesangial cells led to increased proliferation and expression of matrix proteins fibronectin and collagen IV. Conversely, a reduction in both proliferation and fibronectin deposition was observed in diabetic PAR-1 deficient mice. Overall, we show that PAR-1 plays an important role in the development of DN and PAR-1 might therefore be an attractive therapeutic target to pursue in DN.
Chronic Moderate Alcohol Intakes Accelerate SR-B1 Mediated Reverse Cholesterol Transport
Authors: Li Menghua , Diao Yan , Liu Ying , Huang Hui , Li Yanze , Tan Peizhu , Liang Huan , He Qi , Nie Junhui , Dong Xingli , Wang Yang , Zhou Lingyun , Gao Xu
Published: September 2016

Cholesterol is essential for all animal life. However, a high level of cholesterol in the body is strongly associated with the progression of various severe diseases. In our study, the potential involvement of alcohol in the regulation of high density lipoprotein (HDL) receptor scavenger receptor class B and type I (SR-B1)-mediated reverse cholesterol transport was investigated. We separated male C57BL/6 mice into four diets: control, alcohol, Control + HC and alcohol + HC. The SR-B1 level and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate- high- density lipoprotein (DiI-HDL) uptake were also measured in AML12 cells and HL7702 cells treated with alcohol. The control + HC diet led to increased hepatic triglyceride and cholesterol levels while alcohol + HC led no significant change. Compared with that of the control group, the SR-B1 mRNA level was elevated by 27.1% (P < 0.05), 123.8% (P < 0.001) and 343.6% (P < 0.001) in the alcohol, control + HC and alcohol + HC groups, respectively. In AML12 and HL7702 cells, SR-B1 level and DiI-HDL uptake were repressed by SR-B1 siRNA or GW9662. However, these effects were reversed through alcohol treatment. These data suggest that a moderate amount of alcohol plays a novel role in reverse cholesterol transport, mainly mediated by PPARγ and SR-B1.
Patterns of contribution to citizen science biodiversity projects increase understanding of volunteers’ recording behaviour
Authors: Boakes Elizabeth H. , Gliozzo Gianfranco , Seymour Valentine , Harvey Martin , Smith Chloë , Roy David B. , Haklay Muki
Published: September 2016

The often opportunistic nature of biological recording via citizen science leads to taxonomic, spatial and temporal biases which add uncertainty to biodiversity estimates. However, such biases may also give valuable insight into volunteers’ recording behaviour. Using Greater London as a case-study we examined the composition of three citizen science datasets – from Greenspace Information for Greater London CIC, iSpot and iRecord - with respect to recorder contribution and spatial and taxonomic biases, i.e. when, where and what volunteers record. We found most volunteers contributed few records and were active for just one day. Each dataset had its own taxonomic and spatial signature suggesting that volunteers’ personal recording preferences may attract them towards particular schemes. There were also patterns across datasets: species’ abundance and ease of identification were positively associated with number of records, as was plant height. We found clear hotspots of recording activity, the 10 most popular sites containing open water. We note that biases are accrued as part of the recording process (e.g. species’ detectability) as well as from volunteer preferences. An increased understanding of volunteer behaviour gained from analysing the composition of records could thus enhance the fit between volunteers’ interests and the needs of scientific projects.
Targeting Motor End Plates for Delivery of Adenoviruses: An Approach to Maximize Uptake and Transduction of Spinal Cord Motor Neurons
Authors: Tosolini Andrew Paul , Morris Renée
Published: September 2016

Gene therapy can take advantage of the skeletal muscles/motor neurons anatomical relationship to restrict gene expression to the spinal cord ventral horn. Furthermore, recombinant adenoviruses are attractive viral-vectors as they permit spatial and temporal modulation of transgene expression. In the literature, however, several inconsistencies exist with regard to the intramuscular delivery parameters of adenoviruses. The present study is an evaluation of the optimal injection sites on skeletal muscle, time course of expression and mice’s age for maximum transgene expression in motor neurons. Targeting motor end plates yielded a 2.5-fold increase in the number of transduced motor neurons compared to injections performed away from this region. Peak adenoviral transgene expression in motor neurons was detected after seven days. Further, greater numbers of transduced motor neurons were found in juvenile (3–7 week old) mice as compared with adults (8+ weeks old). Adenoviral injections produced robust transgene expression in motor neurons and skeletal myofibres. In addition, dendrites of transduced motor neurons were shown to extend well into the white matter where the descending motor pathways are located. These results also provide evidence that intramuscular delivery of adenovirus can be a suitable gene therapy approach to treat spinal cord injury.
Crystal structures of archaeal 2-oxoacid:ferredoxin oxidoreductases from Sulfolobus tokodaii
Authors: Yan Zhen , Maruyama Akane , Arakawa Takatoshi , Fushinobu Shinya , Wakagi Takayoshi
Published: September 2016

As the first three-dimensional structure of the two-subunit type 2-oxoacid:ferredoxin oxidoreductases (OFOR) from archaea, we solved the crystal structures of STK_23000/STK_22980 (StOFOR1) and STK_24350/STK_24330 (StOFOR2) from Sulfolobus tokodaii. They showed similar overall structures, consisting of two a- and b-subunit heterodimers containing thiamin pyrophosphate (TPP) cofactor and [4Fe-4S] cluster, but lack an intramolecular ferredoxin domain. Unlike other OFORs, StOFORs can utilize both pyruvate and 2-oxoglutarate, playing a key role in the central metabolism. In the structure of StOFOR2 in unreacted pyruvate complex form, carboxylate group of pyruvate is recognized by Arg344 and Thr257 from the a-subunit, which are conserved in pyruvate:ferredoxin oxidoreductase from Desulfovbrio africanus (DaPFOR). In the structure of StOFOR1 co-crystallized with 2-oxobutyrate, electron density corresponding to a 1-hydroxypropyl group (post-decarboxylation state) was observed at the thiazole ring of TPP. The binding pockets of the StOFORs surrounding the methyl or propyl group of the ligands are wider than that of DaPFOR. Mutational analyses indicated that several residues were responsible for the broad 2-oxoacid specificity of StOFORs. We also constructed a possible complex structural model by placing a Zn2+-containing dicluster ferredoxin of S. tokodaii into the large pocket of StOFOR2, providing insight into the electron transfer between the two redox proteins.
Magneto-Optical Study of Defect Induced Sharp Photoluminescence in LaAlO3 and SrTiO3
Authors: Sarkar Soumya , Saha Surajit , Motapothula M. R. , Patra Abhijeet , Cao Bing-Chen , Prakash Saurav , Cong Chun Xiao , Mathew Sinu , Ghosh Siddhartha , Yu Ting , Venkatesan T.
Published: September 2016

Strongly correlated electronic systems such as Transition Metal Oxides often possess various mid-gap states originating from intrinsic defects in these materials. In this paper, we investigate an extremely sharp Photoluminescence (PL) transition originating from such defect states in two widely used perovskites, LaAlO3 and SrTiO3. A detailed study of the PL as a function of temperature and magnetic field has been conducted to understand the behavior and origin of the transition involved. The temperature dependence of the PL peak position for SrTiO3 is observed to be opposite to that in LaAlO3. Our results reveal the presence of a spin/orbital character in these transitions which is evident from the splitting of these defect energy levels under a high magnetic field. These PL transitions have the potential for enabling non-contact thermal and field sensors.
Probing the luminal microenvironment of reconstituted epithelial microtissues
Authors: Cerchiari Alec E. , Samy Karen E. , Todhunter Michael E. , Schlesinger Erica , Henise Jeff , Rieken Christopher , Gartner Zev J. , Desai Tejal A.
Published: September 2016

Polymeric microparticles can serve as carriers or sensors to instruct or characterize tissue biology. However, incorporating microparticles into tissues for in vitro assays remains a challenge. We exploit three-dimensional cell-patterning technologies and directed epithelial self-organization to deliver microparticles to the lumen of reconstituted human intestinal microtissues. We also develop a novel pH-sensitive microsensor that can measure the luminal pH of reconstituted epithelial microtissues. These studies offer a novel approach for investigating luminal microenvironments and drug-delivery across epithelial barriers.
De novo Transcriptome Analysis Reveals Distinct Defense Mechanisms by Young and Mature Leaves of Hevea brasiliensis (Para Rubber Tree)
Authors: Fang Yongjun , Mei Hailiang , Zhou Binhui , Xiao Xiaohu , Yang Meng , Huang Yacheng , Long Xiangyu , Hu Songnian , Tang Chaorong
Published: September 2016

Along with changes in morphology in the course of maturation, leaves of Hevea brasiliensis become more resistant to leaf diseases, including the South American Leaf Blight (SALB), a devastating fungal disease of this economically important tree species. To understand the underlying mechanisms of this defense, and to identify the candidate genes involved, we sequenced the Hevea leaf transcriptome at four developmental stages (I to IV) by Illumina sequencing. A total of 62.6 million high-quality reads were generated, and assembled into 98,796 unique transcripts. We identified 3,905 differentially expressed genes implicated in leaf development, 67.8% (2,651) of which were during the transition to leaf maturation. The genes involved in cyanogenic metabolism, lignin and anthocyanin biosynthesis were noteworthy for their distinct patterns of expression between developing leaves (stages I to III) and mature leaves (stage IV), and the correlation with the change in resistance to SALB and the Oidium/Colletotrichum leaf fall. The results provide a first profile of the molecular events that relate to the dynamics of leaf morphology and defense strategies during Hevea leaf development. This dataset is beneficial to devising strategies to engineer resistance to leaf diseases as well as other in-depth studies in Hevea tree.