bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly via Robust Neuronal Differentiation
Authors: Uchida Hiroki , Morita Takahiro , Niizuma Kuniyasu , Kushida Yoshihiro , Kuroda Yasumasa , Wakao Shohei , Sakata Hiroyuki , Matsuzaka Yoshiya , Mushiake Hajime , Tominaga Teiji , Borlongan Cesario V. , Dezawa Mari
Published: September 2015

Objective: Muse cells reside as pre-existing pluripotent-like stem cells within the fibroblasts, are nontumorigenic, exhibit differentiation capacity into triploblastic-lineage cells, and replenish lost cells when transplanted in injury models. Cell fate and function of human skin fibroblast-derived Muse cells were evaluated in a rat stroke model. Methods: Muse cells (30,000), collected by pluripotent surface marker stage-specific embryonic antigen-3, were injected stereotaxically into three deposits within the rat ischemic cortex at 2 days after transient middle cerebral artery occlusion, and the cells' biological effects were examined for more than 84 days. Results: Muse cells spontaneously and promptly committed to neural/neuronal-lineage cells when cocultured with stroke brain slices. Muse-transplanted stroke rats exhibited significant improvements in neurological and motor functions compared to control groups at chronic days 70 and 84, without a reduction in the infarct size. Muse cells survived in the host brain for up to 84 days and differentiated into NeuN (∼65%), MAP-2 (∼32%), calbindin (∼28%), and GST-π (∼25%)-positive cells in the cortex, but glial fibrillary acidic protein-positive cells were rare. Tumor formation was not observed. Muse cells integrated into the sensory-motor cortex, extended their neurites into cervical spinal cord, and displayed normalized hind limb somatosensory evoked potentials. Interpretation: Muse cells are unique from other stem cells in that they differentiate with high ratio into neuronal cells after integration with host brain microenvironment, possibly reconstructing the neuronal circuit to mitigate stroke symptoms. Human fibroblast-derived Muse cells pose as a novel source of transplantable stem cells, circumventing the need for gene manipulations, especially when contemplating autologous cell therapy for stroke.
Teachers' Adaptive Instruction Supporting Students' Literacy Learning
Authors: Vaughn Margaret , Parsons Seth A. , Gallagher Melissa A. , Branen Jeneille
Published: September 2015

Adaptive teaching is an instructional approach where differences among learners are clearly recognized. For the last decade, our research team has studied literacy teachers' instructional adaptations in numerous classrooms in different regions of the United States. In this article, we share conclusions and insights from this longitudinal research. Specifically, we describe the characteristics of teachers who adapt their literacy instruction to support the individual needs of their students. Our aim is to support practicing teachers in their efforts to teach adaptively as they negotiate literacy instruction in today's diverse classrooms.
Longitudinal changes in maternal serum placental growth factor and soluble fms‐like tyrosine kinase‐1 in women at increased risk of pre‐eclampsia
Authors: Khalil A. , Maiz N. , Garcia‐Mandujano R. , Penco J. M. , Nicolaides K. H.
Published: September 2015

Objectives

To investigate longitudinal changes in maternal serum levels of placental growth factor (PlGF) and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) in pregnant women who develop pre‐eclampsia (PE) or gestational hypertension (GH).

Methods

This was a prospective longitudinal study in women with singleton pregnancies identified by screening at 11 + 0 to 13 + 6 weeks' gestation as being at high‐risk of PE. Blood samples were taken every 4 weeks until delivery. Values were compared in women who developed preterm PE (requiring delivery before 37 weeks' gestation), term PE or GH and those who remained normotensive.

Results

A total of 1069 samples were analyzed in 234 women, including 172 who remained normotensive, 18 who developed GH, 22 who developed preterm PE and 22 who developed term PE. In the preterm PE group, compared to the normotensive group, sFlt‐1 levels were significantly higher from 15 weeks' gestation onward and the difference increased with gestational age (P < 0.001). In the preterm PE group, compared to the normotensive group, PlGF levels were significantly lower from 11 weeks' gestation onward and the difference increased significantly with gestational age (P < 0.001). Similarly, in the term PE and GH groups, PlGF levels were lower from 13 and 27 weeks onward, respectively, and the differences increased significantly with gestational age (P < 0.001 for both groups). In the preterm PE group, compared to the normotensive group, the sFlt‐1/PlGF ratio was significantly higher from 11 weeks onward and the difference increased significantly with gestational age (P < 0.001). A random slope model provided a significantly better fit to the data than did a single‐level model for sFlt‐1 (likelihood ratio (LR) = 516; degrees of freedom (df) = 3; P < 0.001), PlGF (LR = 542; df = 3; P < 0.001) and the sFlt‐1/PlGF ratio (LR = 468; df = 3; P < 0.001).

Conclusion

Repeat measurements of the biochemical markers used in this study are likely to be better predictors of PE than are measurements at a single time point during pregnancy, as the differences between normotensive and hypertensive pregnancies increase with gestational age. In screening for preterm PE, maternal serum level of PlGF is a useful marker from the first trimester onward, while the level of sFlt‐1 is likely to have a predictive value from the second trimester onward. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Transcriptomic profiling of chemical exposure reveals roles of Yap1 in protecting yeast cells from oxidative and other types of stresses
Authors: Zhang Chao , Li Zhouquan , Zhang Xiaohua , Yuan Li , Dai Heping , Xiao Wei
Published: September 2015

Transcriptomic profiles are generated by comparing wild‐type and the yeast yap1 mutant to various chemicals in an attempt to establish a correlation between this gene mutation and chemical exposure. Test chemicals include ClonNAT as a non‐genotoxic agent, methyl methanesulphonate (MMS) as an alkylating agent, tert‐butyl hydroperoxide (t‐BHP) as an oxidative agent and the mixture of t‐BHP and MMS to reflect complex natural exposure. Differentially expressed genes (DEGs) were identified and specific DEGs were obtained by excluding overlapping DEGs with the control group. In the MMS exposure group, deoxyribonucleotide biosynthetic processes were upregulated, while oxidation–reduction processes were downregulated. In the t‐BHP exposure group, metabolic processes were upregulated while peroxisome and ion transport pathways were downregulated. In the mixture exposure group, the proteasome pathway was upregulated, while the aerobic respiration was downregulated. Homologue analysis of DEGs related to human diseases showed that many of DEGs were linked to cancer, ageing and neuronal degeneration. These observations confirm that the yap1 mutant is more sensitive to chemicals than wild‐type cells and that the susceptible individuals carrying the YAP1‐like gene defect may enhance risk to chemical exposure. Hence, this study offers a novel approach to environmental risk assessment, based on the genetic backgrounds of susceptible individuals. Copyright © 2015 John Wiley & Sons, Ltd.
Three Isostructural 4‐Sulfophthalate‐Based Lanthanide Complexes: Syntheses, Crystal Structures, and Luminescent Properties
Authors: Shang Qiu , Li Yan , Yang En‐Cui , Zhao Xiao‐Jun
Published: September 2015

Three lanthanide complexes with the ligand 4‐sulfophthalate (sp3–), [Ln(H2O)2(sp)]n [Ln = Dy (1), Tb (2), and Er (3)], were solvo‐/hydrothermally synthesized by changing the rare earth cations, and were characterized structurally and photophysically. Complexes 1–3 are isostructural, exhibiting a two‐dimensional layered structure with centrosymmetric dinuclear subunits infinitely extended by 4‐connected sp3– connectors. Photoluminescence spectra of 1–3 demonstrate that anionic sp3– ligand can serve as a functionalized chromophore to sensitize the luminescent emission of the lanthanide ion, suggesting that the sp3–‐involved lanthanide complexes can be used as novel optical materials.
Theoretically Predicted and Experimentally Observed Relaxation Pathways of two Heterodinuclear 3d‐4f Complexes
Authors: Bender Markus , Comba Peter , Demeshko Serhiy , Großhauser Michael , Müller Dennis , Wadepohl Hubert
Published: September 2015

The dinucleating ligand (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayl)‐tetrakis‐(methylene)‐tetrakis(2‐methoxy‐4‐methylphenol), H4L, is well preorganized with an N4O2 octahedral site for a divalent transition metal ion and an O4 site (phenolates and methoxo donors, completed by added pivalates and solvent molecules) for lanthanide ions. Two 3d‐4f complexes ([DyIII{NiII(μ‐H2L)}piv2(OH2)]ClO4 and [DyIII{CoII(μ‐H2L)}piv2(OH2)]ClO4) were prepared and fully characterized by X‐ray molecular structures and electronic properties determined by ac and dc SQUID magnetometry. While the NiII based complex shows single‐molecule magnetism (SMM), the CoII complex does not. With an extensive quantum‐chemical analysis, this is shown to be due to a misalignment of the single ion anisotropies in the latter complex, and reasons for this are discussed.
Ligand Exchange Processes in Abnormal N‐heterocyclic Carbene Rhodium Complexes
Authors: Krüger Anneke , Michaud Gaëlle , Dowling Aoife , Müller‐Bunz Helge , Albrecht Martin
Published: September 2015

Rhodium(III) complexes containing a mesoionic and strongly electron‐donating abnormal dicarbene ligand and a phosphine in a facial coordination mode and three ancillary iodide ligands undergo spontaneous solvolysis to give a cationic complex with an iodide in the outer coordination sphere. The availability of this non‐coordinating iodide promotes a halide exchange reaction and in chlorinated solvents such as chlorocyclohexane, chloroethyl benzene, 1,2‐dichloroethane, and benzyl chloride, the metal‐coordinated iodo ligands exchange for chlorides. Mechanistic investigations suggest that the role of the metal is to release the iodide anion, rather than being directly involved in the C–Cl bond activation. The release of the iodide from the metal coordination sphere is promoted by the strong donor ability of the abnormal dicarbene ligand.
Persisting Differences or Adaptation to German Fertility Patterns? First and Second Birth Behavior of the 1.5 and Second Generation Turkish Migrants in Germany
Authors: Krapf Sandra , Wolf Katharina
Published: September 2015

In this study, we use data of the German Mikrozensus to explore first and second birth behavior of migrants’ descendants. Whereas prior waves of the Mikrozensus only included respondents’ citizenship, in the survey years 2005 and 2009 also parental citizenship has been surveyed. This allows us to identify respondents’ migrant backgrounds, even if they have German citizenship. We distinguish those who migrated as children (1.5 generation) from those who were born to Turkish parents in Germany (second generation migrants). We compare both migrant generations to German non-migrants. Using discrete-time hazard models, our results show that 1.5 generation migrants have the highest probability of having a first and second birth, while German non-migrants have the lowest birth probabilities. The second generation lies in-between. This pattern also persists after taking the educational attainment of respondents into consideration. However, there seems to be an adaptation of highly educated second generation Turkish migrants to non-migrant Germans: we find no significant differences in the probability of having a first birth in the two groups. For second births, we do not find this pattern which might be related to the young age structure in the sample of second generation migrants.
Changes in the Determinants of Marriage Entry in Post-Reform Urban China
Authors: Yu Jia , Xie Yu
Published: September 2015

Using population intercensus and national survey data, we examine marriage timing in urban China spanning the past six decades. Descriptive analysis from the intercensus shows that marriage patterns have changed in China. Marriage age is delayed for both men and women, and prevalence of nonmarriage became as high as one-quarter for men in recent birth cohorts with very low levels of education. Capitalizing on individual-level survey data, we further explore the effects of demographic and socioeconomic determinants of entry into marriage in urban China over time. Our study yields three significant findings. First, the influence of economic prospects on marriage entry has significantly increased during the economic reform era for men. Second, the positive effect of working in the state-owned sector has substantially weakened. Third, educational attainment now has a negative effect on marriage timing for women. Taken together, these results suggest that the traditional hypergamy norm has persisted in China as an additional factor in the influences of economic resources on marriage formation.
Lost in transaction? The transfer effect of strategic consistency
Authors: Fehre Kerstin , Kronenwett Daniel , Lindstädt Hagen , Wolff Michael
Published: September 2015

Prior empirical studies provide evidence that the learning-curve perspective from manufacturing settings is not directly applicable to strategic management settings. In the latter case learning relates to the quality rather than to the quantity of experience. Regarding the antecedents of organizational learning especially, there are still unanswered questions remaining; for example, the questions what kind of experience has a positive effect on performance and what kind of experience is more of a hindrance than a help. This becomes obvious when looking at acquisitions as examples of strategic management decisions. Results of prior empirical studies analyzing the relationship of acquisition experience and acquisition performance have been mixed. By introducing the concept of strategic consistency, we intend to facilitate a better understanding of the kind of experience necessary for organizational learning. Therefore, we measure the concordance and frequency of change in strategic actions. Employing a sample of 379 acquisition series, we find evidence for a positive transfer effect of strategic consistency within series and, therefore, a positive relationship between strategic consistency and acquisition performance.
Generation of an alpaca‐derived nanobody recognizing γ‐H2AX
Authors: Rajan Malini , Mortusewicz Oliver , Rothbauer Ulrich , Hastert Florian D. , Schmidthals Katrin , Rapp Alexander , Leonhardt Heinrich , Cardoso M. Cristina
Published: September 2015

Post‐translational modifications are difficult to visualize in living cells and are conveniently analyzed using antibodies. Single‐chain antibody fragments derived from alpacas and called nanobodies can be expressed and bind to the target antigenic sites in living cells. As a proof of concept, we generated and characterized nanobodies against the commonly used biomarker for DNA double strand breaks γ‐H2AX.In vitro andin vivo characterization showed the specificity of the γ‐H2AX nanobody. Mammalian cells were transfected with fluorescent fusions called chromobodies and DNA breaks induced by laser microirradiation. We found that alternative epitope recognition and masking of the epitope in living cells compromised the chromobody function. These pitfalls should be considered in the future development and screening of intracellular antibody biomarkers.
The Spiral to Recovery: An Australian Model for Therapeutic Residential Care
Authors: Downey Laurel , Jago Jon , Poppi Shanelle
Published: September 2015

This article gives a brief overview of the Spiral to Recovery practice framework as it is being used at Catalyst child and family services in far north Queensland. The Spiral is an evidence informed framework for therapeutic residential care (TRC), designed for children and young people with complex and extreme emotional and behavioural difficulties who reside in out-of-home care (OOHC) placements. The Spiral is a stage-based framework where the initial aim is to establish actual and felt safety before young people meet the challenges of healing and growth. The framework rests on a theoretical base of trauma, attachment and socialisation theories. The article also describes how the Spiral framework has been implemented at Catalyst, demonstrating the need for congruence between organisational and practice frameworks.
Why Two Parties? Ambition, Policy, and the Presidency
Authors: Aldrich John H. , Lee Daniel J.
Published: September 2015

Duverger’s Law suggests that two parties will dominate under first-past-the-post (FPTP) within an electoral district, but the law does not necessarily establish two-party competition at the national level. United States is unique among FPTP countries in having the only durable and nearly pure, two-party system. Following this observation, we answer two questions. First, what contributes to the same two parties competing in districts all across the country and at different levels of office? Second, why is the US two-party system so durable over time, dominated by the same two parties? That is, “Why two parties?” As an answer, we propose the APP: ambition, the presidency, and policy. The presidency with its national electorate and electoral rules that favor two-party competition establishes two national major parties, which frames the opportunity structure that influences party affiliation decisions of ambitious politicians running for lower offices. Control over the policy agenda helps reinforce the continuation of a particular two-party system in equilibrium by blocking third parties through divergence on the main issue dimension and the suppression of latent issue dimensions that could benefit new parties. The confluence of the three factors explains why the United States is so uniquely a durable two-party system.
Effects of functional remediation on neurocognitively impaired bipolar patients: enhancement of verbal memory
Authors: Bonnin C. M. , Reinares M. , Martínez-Arán A. , Balanzá-Martínez V. , Sole B. , Torrent C. , Tabarés-Seisdedos R. , García-Portilla M. P. , Ibáñez A. , Amann B. L. , Arango C. , Ayuso-Mateos J. L. , Crespo J. M. , González-Pinto A. , Colom F. , Vieta E. ,   The CIBERSAM Functional Remediation Group
Published: September 2015

Background

Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients.

Method

A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants’ neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients.

Results

Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F2,158 = 4.26, df = 2, p = 0.016).

Conclusions

Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.
Norm antipreneurs and theorising resistance to normative change
Authors: BLOOMFIELD ALAN
Published: September 2015

Norm dynamics studies typically accord a special status to norm entrepreneurs, actors who promote new global norms. But conceptually privileging these agents of change has meant the norm dynamics literature has become unbalanced and marred by case selection bias. Accordingly, an oppositional role – the ‘norm antipreneur’ – should be recognised to correct these problems. When the normative status quo in an issue-area isentrenched, a clear distinction can be drawn between the entrepreneurs and antipreneurs, because in these contexts the antipreneurs enjoy significant but under-appreciated tactical and strategic advantages. Recognising this enables the construction of a norm dynamics role-spectrum – a sort of ‘typology of roles’ – including ‘competitor entrepreneur’ and ‘creative resister’ in addition to the entrepreneur and antipreneur roles which actors might play in particular norm contestation contexts. Understanding these roles promises to improve analyses of the dynamic interactions between actors in particular norm contestation processes, thereby bringing greater overall balance to the norm dynamics literature.1
The nomadic other: Ontological security and the Inner Asian steppe in historical East Asian international politics
Authors: MacKay Joseph
Published: September 2015

A growing literature in IR addresses the historical international politics of East Asia prior to Western influence. However, this literature has taken little note of the role of Eurasian steppe societies and empires in these dynamics. This article offers a corrective, showing that relations between China and the steppe played an important role in regional politics. I argue that Chinese elite conceptions of the steppe as other played an important role in maintaining China’s ontological security. Imperial Chinese elites pursued a deliberate strategy of ‘othering’ steppe societies, presenting them as China’s political-cultural opposite. Doing so both provided a source of stable identity to China and justified their exclusion from the Chinese ‘world order’. Empirically, I proceed in three sections. First, I consider Chinese identity building, framed in terms of ontological security, both under the founding Qin and Han dynasties, and under the later Ming dynasty. Second, I address recent historiography of the steppe, showing Chinese conceptions of it were inaccurate. Third, I address the long history of hybridity between the two regions.
Introduction: Prosody in the Nordic languages
Authors: Horne Merle , Roll Mikael
Published: September 2015

The initiative for this special issue on prosody in the Nordic languages developed in connection with an international symposium on prosody which took place in Lund on 2–3 June 2014 (http://konferens.ht.lu.se/en/bruce-2014/). The symposium commemorated the life and work of Gösta Bruce (1947–2010), our friend, teacher, mentor, and colleague during many years. Gösta's contributions to the field of prosody have been of utmost significance to the development of prosody research, in particular his work on modelling the structure and function of Swedish word accents ‘in sentence perspective’.
Study on Initial Gravity Map Matching Technique Based on Triangle Constraint Model
Authors: Zhuangsheng Zhu , Yiyang Guo , Zhenli Yang
Published: September 2015

In this paper, a gravity map-matching algorithm is proposed based on a triangle constraint model. A high-accuracy triangle constraint model is constructed by using a short time and high-accuracy-featured inertial navigation system. In this paper, the principle of the gravity map-matching algorithm based on the triangle constraint model and a triangle matching parameter-parsing method are first introduced in detail. It is verified by test that the method is sensitive to the initial error value. By comparison to the commonly used Iterative Closest Contour Point (ICCP) and Sandia Inertial Terrain Aided Navigation (SITAN) algorithms respectively, the results show that this method is perfect in real-time performance and reliability, and its advantages are more obvious especially with a large initial error.
Bayesian Inference of GNSS Failures
Authors: Milner Carl , Macabiau Christophe , Thevenon Paul
Published: September 2015

The probability of failure (failure rate) is a key input parameter to integrity monitoring systems used for safety, liability or mission critical applications. A standard approach in the design of Global Positioning System (GPS) integrity monitoring is to utilise the service commitment on the probability of major service failure, often by applying a conservative factor. This paper addresses the question of what factor is appropriate by applying Bayesian inference to real and hypothetical fault histories.

Global Navigation Satellite System (GNSS) anomalies include clock or signal transmission type faults which are punctual (may occur at any time) and incorrect ephemeris data which are broadcast for a nominal two hours. These two types of anomaly, classified as continuous and discrete respectively are addressed. Bounds on the total probability of failure are obtained with given confidence levels subject to well defined hypotheses relating past to future performance. Factors for the GPS service commitment of 10−5per hour per satellite are obtained within the range two to five with high confidence (up to 1–10−9).
Revisiting Wolff–Parkinson–White risk stratification: a malignant arrhythmia in a patient with intermittent pre-excitation
Authors: Paul Erin A. , Mone Suzanne M. , Liberman Leonardo
Published: September 2015

It has been reported that the presence of intermittent pre-excitation indicates low risk of rapid conduction via the accessory pathway in atrial fibrillation. We report a case of a 10-year-old boy with a history of intermittent pre-excitation who presented with atrial fibrillation with very rapid conduction.
Five-fold symmetry as indicator of dynamic arrest in metallic glass-forming liquids
Authors: Hu Y. C. , Li F. X. , Li M. Z. , Bai H. Y. , Wang W. H.
Published: September 2015

With sufficient high cooling rates, a variety of liquids, including metallic melts, will cross a glass transition temperature and solidify into glass accompanying a marked increase of the shear viscosity in approximately 17 orders of magnitude. Because of the intricate atomic structure and dynamic behaviours of liquid, it is yet difficult to capture the underlying structural mechanism responsible for the marked slowing down during glass transition, which impedes deep understanding of the formation and nature of glasses. Here, we report that a universal structural indicator, the average degree of five-fold local symmetry, can well describe the slowdown dynamics during glass transition. A straightforward relationship between structural parameter and viscosity (or α-relaxation time) is introduced to connect the dynamic arrest and the underlying structural evolution. This finding would be helpful in understanding the long-standing challenges of glass transition mechanism in the structural perspective.
New insights into photoactivated volume generation boost surface morphing in liquid crystal coatings
Authors: Liu Danqing , Broer Dirk J.
Published: September 2015

Photoactivated generation of disorder in a liquid crystal network produces free volume that leads to the controlled formation of dynamic corrugations at its surface. The liquid crystal order amplifies the deformation of copolymerized azobenzene, which takes place on molecular length scales, to a micrometre-sized macroscopic phenomenon based on changes in density. We postulate a new mechanism in which continuous oscillating dynamics of the trans-to-cis isomerization of the azobenzene overrules the net conversion, which is currently considered as the origin. This is supported by a significant local density decrease when both the trans and cis isomers are triggered simultaneously, either by dual-wavelength excitation or by the addition of a fluorescent agent converting part of the light to the cis-actuating wavelengths. This new insight provides a general guideline to boost free volume generation leading not only to larger macroscopic deformations but also to controllable and faster non-equilibrium dynamics.
Probe-based measurement of lateral single-electron transfer between individual molecules
Authors: Steurer Wolfram , Fatayer Shadi , Gross Leo , Meyer Gerhard
Published: September 2015

The field of molecular electronics aims at using single molecules as functional building blocks for electronics components, such as switches, rectifiers or transistors. A key challenge is to perform measurements with atomistic control over the alignment of the molecule and its contacting electrodes. Here we use atomic force microscopy to examine charge transfer between weakly coupled pentacene molecules on insulating films with single-electron sensitivity and control over the atomistic details. We show that, in addition to the imaging capability, the probe tip can be used to control the charge state of individual molecules and to detect charge transfers to/from the tip, as well as between individual molecules. Our approach represents a novel route for molecular charge transfer studies with a host of opportunities, especially in combination with single atom/molecule manipulation and nanopatterning techniques.
Atomically resolved real-space imaging of hot electron dynamics
Authors: Lock D. , Rusimova K. R. , Pan T. L. , Palmer R. E. , Sloan P. A.
Published: September 2015

The dynamics of hot electrons are central to understanding the properties of many electronic devices. But their ultra-short lifetime, typically 100 fs or less, and correspondingly short transport length-scale in the nanometre range constrain real-space investigations. Here we report variable temperature and voltage measurements of the nonlocal manipulation of adsorbed molecules on the Si(111)-7 × 7 surface in the scanning tunnelling microscope. The range of the nonlocal effect increases with temperature and, at constant temperature, is invariant over a wide range of electron energies. The measurements probe, in real space, the underlying hot electron dynamics on the 10 nm scale and are well described by a two-dimensional diffusive model with a single decay channel, consistent with 2-photon photo-emission (2PPE) measurements of the real time dynamics.
Correction: Corrigendum: NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma
Authors: Wilson C. L. , Jurk D. , Fullard N. , Banks P. , Page A. , Luli S. , Elsharkawy A. M. , Gieling R. G. , Bagchi Chakraborty J. , Fox C. , Richardson C. , Callaghan K. , Blair G. E. , Fox N. , Lagnado A. , Passos J. F. , Moore A. J. , Smith G. R. , Tiniakos D. G. , Mann J. , Oakley F. , Mann D. A.
Published: September 2015

Nature Communications 6, Article number: 6818 (2015); Published 16 April 2015; Updated 21 September 2015 The diagram in Supplementary Fig. 6a illustrating the targeting strategy for the nfkb1S340A KI allele depicts an unrelated targeting strategy. The correct version of the figure appears below. Supplementary Figure 6
High-resolution computed tomography reconstructions of invertebrate burrow systems
Authors: Hale Rachel , Boardman Richard , Mavrogordato Mark N. , Sinclair Ian , Tolhurst Trevor J. , Solan Martin
Published: September 2015

The architecture of biogenic structures can be highly influential in determining species contributions to major soil and sediment processes, but detailed 3-D characterisations are rare and descriptors of form and complexity are lacking. Here we provide replicate high-resolution micro-focus computed tomography (μ-CT) data for the complete burrow systems of three co-occurring, but functionally contrasting, sediment-dwelling inter-tidal invertebrates assembled alone, and in combination, in representative model aquaria. These data (≤2,000 raw image slices aquarium−1, isotropic voxel resolution, 81 μm) provide reference models that can be used for the development of novel structural analysis routines that will be of value within the fields of ecology, pedology, geomorphology, palaeobiology, ichnology and mechanical engineering. We also envisage opportunity for those investigating transport networks, vascular systems, plant rooting systems, neuron connectivity patterns, or those developing image analysis or statistics related to pattern or shape recognition. The dataset will allow investigators to develop or test novel methodology and ideas without the need to generate a complete three-dimensional computation of exemplar architecture.
Multiplexed 3D FRET imaging in deep tissue of live embryos
Authors: Zhao Ming , Wan Xiaoyang , Li Yu , Zhou Weibin , Peng Leilei
Published: September 2015

Current deep tissue microscopy techniques are mostly restricted to intensity mapping of fluorophores, which significantly limit their applications in investigating biochemical processes in vivo. We present a deep tissue multiplexed functional imaging method that probes multiple Förster resonant energy transfer (FRET) sensors in live embryos with high spatial resolution. The method simultaneously images fluorescence lifetimes in 3D with multiple excitation lasers. Through quantitative analysis of triple-channel intensity and lifetime images, we demonstrated that Ca2+ and cAMP levels of live embryos expressing dual FRET sensors can be monitored simultaneously at microscopic resolution. The method is compatible with a broad range of FRET sensors currently available for probing various cellular biochemical functions. It opens the door to imaging complex cellular circuitries in whole live organisms.
Correction: Corrigendum: Interactional synchrony in chimpanzees: Examination through a finger-tapping experiment
Authors: Yu Lira , Tomonaga Masaki
Published: September 2015

Humans often unconsciously coordinate behaviour with that of others in daily life. This interpersonal coordination, including mimicry and interactional synchrony, has been suggested to play a fundamental role in social interaction. If this coordinative behavior is socially adaptive, it may be shared with other highly social animal species. The current study targeted chimpanzees, which phylogenetically are the closest living relatives of humans and live in complex social groups, and examined whether interactional synchrony would emerge in pairs of chimpanzees when auditory information about a partner’s movement was provided. A finger-tapping task was introduced via touch panels to elicit repetitive and rhythmic movement from each chimpanzee. We found that one of four chimpanzees produced significant changes in both tapping tempo and timing of the tapping relative to its partner’s tap when auditory sounds were provided. Although the current results may have limitations in generalizing to chimpanzees as a species, we suggest that a finger-tapping task is one potential method to investigate interactional synchrony in chimpanzees under a laboratory setup.
Erratum: Novel microscopy-based screening method reveals regulators of contact-dependent intercellular transfer
Authors: Frei Dominik Michael , Hodneland Erlend , Rios-Mondragon Ivan , Burtey Anne , Neumann Beate , Bulkescher Jutta , Schölermann Julia , Pepperkok Rainer , Gerdes Hans-Hermann , Kögel Tanja
Published: September 2015

Contact-dependent intercellular transfer (codeIT) of cellular constituents can have functional consequences for recipient cells, such as enhanced survival and drug resistance. Pathogenic viruses, prions and bacteria can also utilize this mechanism to spread to adjacent cells and potentially evade immune detection. However, little is known about the molecular mechanism underlying this intercellular transfer process. Here, we present a novel microscopy-based screening method to identify regulators and cargo of codeIT. Single donor cells, carrying fluorescently labelled endocytic organelles or proteins, are co-cultured with excess acceptor cells. CodeIT is quantified by confocal microscopy and image analysis in 3D, preserving spatial information. An siRNA-based screening using this method revealed the involvement of several myosins and small GTPases as codeIT regulators. Our data indicates that cellular protrusions and tubular recycling endosomes are important for codeIT. We automated image acquisition and analysis to facilitate large-scale chemical and genetic screening efforts to identify key regulators of codeIT.
A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women
Authors: McMillan Amy , Rulisa Stephen , Sumarah Mark , Macklaim Jean M. , Renaud Justin , Bisanz Jordan E. , Gloor Gregory B. , Reid Gregor
Published: September 2015

Bacterial vaginosis (BV) increases transmission of HIV, enhances the risk of preterm labour and is associated with malodour. Clinical diagnosis often relies on microscopy, which may not reflect the microbiota composition accurately. We use an untargeted metabolomics approach, whereby we normalize the weight of samples prior to analysis, to obtained precise measurements of metabolites in vaginal fluid. We identify biomarkers for BV with high sensitivity and specificity (AUC = 0.99) in a cohort of 131 pregnant and non-pregnant Rwandan women and demonstrate that the vaginal metabolome is strongly associated with bacterial diversity. Metabolites associated with high diversity and clinical BV include 2-hydroxyisovalerate and γ-hydroxybutyrate (GHB), but not succinate, which is produced by bothLactobacillus crispatusand BV-associated anaerobesin vitro. Biomarkers associated with high diversity and clinical BV are independent of pregnancy status and were validated in a blinded replication cohort from Tanzania (n = 45), where we predicted clinical BV with 91% accuracy. Correlations between the metabolome and microbiota identifiedGardnerella vaginalisas a putative producer of GHB and we demonstrate production by this speciesin vitro. This work illustrates how changes in community structure alter the chemical composition of the vagina and identifies highly specific biomarkers for a common condition.
Nanoclusters first: a hierarchical phase transformation in a novel Mg alloy
Authors: Okuda Hiroshi , Yamasaki Michiaki , Kawamura Yoshihito , Tabuchi Masao , Kimizuka Hajime
Published: September 2015

The Mg-Y-Zn ternary alloy system contains a series of novel structures known as long-period stacking ordered (LPSO) structures. The formation process and its key concept from a viewpoint of phase transition are not yet clear. The current study reveals that the phase transformation process is not a traditional spinodal decomposition or structural transformation but, rather a novel hierarchical phase transformation. In this transformation, clustering occurs first and the spatial rearrangement of the clusters induce a secondary phase transformation that eventually lead to two-dimensional ordering of the clusters. The formation process was examined using in situ synchrotron radiation small-angle X-ray scattering (SAXS). Rapid quenching from liquid alloy into thin ribbons yielded strongly supersaturated amorphous samples. The samples were heated at a constant rate of 10 K/min. and the scattering patterns were acquired. The SAXS analysis indicated that small clusters grew to sizes of 0.2 nm after they crystallized. The clusters distributed randomly in space grew and eventually transformed into a microstructure with two well-defined cluster-cluster distances, one for the segregation periodicity of LPSO and the other for the in-plane ordering in segregated layer. This transformation into the LPSO structure concomitantly introduces the periodical stacking fault required for the 18R structures.
Calreticulin is required for development of the cumulus oocyte complex and female fertility
Authors: Tokuhiro Keizo , Satouh Yuhkoh , Nozawa Kaori , Isotani Ayako , Fujihara Yoshitaka , Hirashima Yumiko , Matsumura Hiroyuki , Takumi Kazuhiro , Miyano Takashi , Okabe Masaru , Benham Adam M. , Ikawa Masahito
Published: September 2015

Calnexin (CANX) and calreticulin (CALR) chaperones mediate nascent glycoprotein folding in the endoplasmic reticulum. Here we report that these chaperones have distinct roles in male and female fertility. Canx null mice are growth retarded but fertile. Calr null mice die during embryonic development, rendering indeterminate any effect on reproduction. Therefore, we conditionally ablated Calr in male and female germ cells using Stra8 (mcKO) and Zp3 (fcKO) promoter-driven Cre recombinase, respectively. Calr mcKO male mice were fertile, but fcKO female mice were sterile despite normal mating behavior. Strikingly, we found that Calr fcKO female mice had impaired folliculogenesis and decreased ovulatory rates due to defective proliferation of cuboidal granulosa cells. Oocyte-derived, TGF-beta family proteins play a major role in follicular development and molecular analysis revealed that the normal processing of GDF9 and BMP15 was defective in Calr fcKO oocytes. These findings highlight the importance of CALR in female reproduction and demonstrate that compromised CALR function leads to ovarian insufficiency and female infertility.
Lessons in Protein Design from Combined Evolution and Conformational Dynamics
Authors: Tripathi Swarnendu , Waxham M. Neal , Cheung Margaret S. , Liu Yin
Published: September 2015

Protein-protein interactions play important roles in the control of every cellular process. How natural selection has optimized protein design to produce molecules capable of binding to many partner proteins is a fascinating problem but not well understood. Here, we performed a combinatorial analysis of protein sequence evolution and conformational dynamics to study how calmodulin (CaM), which plays essential roles in calcium signaling pathways, has adapted to bind to a large number of partner proteins. We discovered that amino acid residues in CaM can be partitioned into unique classes according to their degree of evolutionary conservation and local stability. Holistically, categorization of CaM residues into these classes reveals enriched physico-chemical interactions required for binding to diverse targets, balanced against the need to maintain the folding and structural modularity of CaM to achieve its overall function. The sequence-structure-function relationship of CaM provides a concrete example of the general principle of protein design. We have demonstrated the synergy between the fields of molecular evolution and protein biophysics and created a generalizable framework broadly applicable to the study of protein-protein interactions.
REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis
Authors: Kawasaki Yoshihiro , Matsumura Kosuke , Miyamoto Masaya , Tsuji Shinnosuke , Okuno Masumi , Suda Sakiko , Hiyoshi Masaya , Kitayama Joji , Akiyama Tetsu
Published: September 2015

The transcription factor GATA6 is a critical regulator of cell proliferation and development in the gastrointestinal tract. We have recently reported that GATA6 induces the expression of the intestinal stem cell marker LGR5 and enhances the clonogenicity and tumorigenicity of colon cancer cells, but not the growth of these cells cultured under adherent conditions. Here we show that REG4, a member of the regenerating islet-derived (REG) family, is also a target of GATA6. We further demonstrate that REG4 is downregulated by overexpression of miR-363, which suppresses GATA6 expression. Moreover, we show that GATA6-mediated activation of REG4 enhances the growth of colon cancer cells under adherent conditions and is required for their tumorigenicity. Taken together, our findings demonstrate that GATA6 simultaneously induces the expression of genes essential for the growth of colon cancer cells under adherent conditions (REG4) and genes required for their clonogenicity (LGR5) and that the miR-363-GATA6-REG4/LGR5 signaling cascade promotes the tumorigenicity of colon cancer cells.
Strong and highly asymmetrical optical absorption in conformal metal-semiconductor-metal grating system for plasmonic hot-electron photodetection application
Authors: Wu Kai , Zhan Yaohui , Zhang Cheng , Wu Shaolong , Li Xiaofeng
Published: September 2015

We propose an architecture of conformal metal-semiconductor-metal (MSM) device for hot-electron photodetection by asymmetrical alignment of the semiconductor barrier relative to the Fermi level of metals and strong energy localization through plasmonic resonances. Compared with the conventional grating design, the multi-layered grating system under conformal configuration is demonstrated to possess both optical and electrical advantages for high-sensitivity hot-electron photodetection. Finite-element simulation reveals that a strong and highly asymmetrical optical absorption (top metal absorption >99%) can be realized under such a conformal arrangement. An analytical probability-based electrical simulation verifies the strong unidirectional photocurrent, by taking advantage of the extremely high net absorption and a low metal/semiconductor barrier height and predicts that the corresponding photoresponsivity can be ~3 times of that based on the conventional grating design in metal-insulator-metal (MIM) configuration.
Ultrasensitive detection and characterization of molecules with infrared plasmonic metamaterials
Authors: Cheng Fei , Yang Xiaodong , Gao Jie
Published: September 2015

Infrared vibrational spectroscopy is an effective technique which enables the direct probe of molecular fingerprints and such detection can be further enhanced by the emerging engineered plasmonic metamaterials. Here we experimentally demonstrate ultrasensitive detection and characterization of polymer molecules based on an asymmetric infrared plasmonic metamaterial and quantitatively analyze the molecule detection sensitivity and molecule-structure interactions. A sharp, non-radiative Fano resonance supported by the plasmonic metamaterial exhibits strongly enhanced near-field and the resonance frequency is tailored to match the vibrational fingerprint of the target molecule. By utilizing the near-field nature of the plasmonic excitation, significantly enhanced absorption signal of molecules in the infrared spectroscopy are obtained, enabling ultrasensitive detection of only minute quantities of organic molecules. The enhancement of molecular absorption up to 105 fold is obtained and sensitive detection of molecules at zeptomole levels (corresponding to a few tens of molecules within a unit cell) is achieved with high signal-to-noise ratio in our experiment. The demonstrated infrared plasmonic metamaterial sensing platform offers great potential for improving the specificity and sensitivity of label-free, biochemical detection.
Enlargement of choroid plexus in complex regional pain syndrome
Authors: Zhou Guangyu , Hotta Jaakko , Lehtinen Maria K. , Forss Nina , Hari Riitta
Published: September 2015

The choroid plexus, located in brain ventricles, has received surprisingly little attention in clinical neuroscience. In morphometric brain analysis, we serendipitously found a 21% increase in choroid plexus volume in 12 patients suffering from complex regional pain syndrome (CRPS) compared with age- and gender-matched healthy subjects. No enlargement was observed in a group of 8 patients suffering from chronic pain of other etiologies. Our findings suggest involvement of the choroid plexus in the pathogenesis of CRPS. Since the choroid plexus can mediate interaction between peripheral and brain inflammation, our findings pinpoint the choroid plexus as an important target for future research of central pain mechanisms.