bluuebunny/crossref_metadata_2025 huggingface dataset:
Formal Definitions of Unbounded Evolution and Innovation Reveal Universal Mechanisms for Open-Ended Evolution in Dynamical Systems
Authors: Adams Alyssa , Zenil Hector , Davies Paul C. W. , Walker Sara Imari
Published: April 2017

Open-ended evolution (OEE) is relevant to a variety of biological, artificial and technological systems, but has been challenging to reproducein silico. Most theoretical efforts focus on key aspects of open-ended evolution as it appears in biology. We recast the problem as a more general one in dynamical systems theory, providing simple criteria for open-ended evolution based on two hallmark features: unbounded evolution and innovation. We define unbounded evolution as patterns that are non-repeating within the expected Poincare recurrence time of an isolated system, and innovation as trajectories not observed in isolated systems. As a case study, we implement novel variants of cellular automata (CA) where the update rules are allowed to vary with time in three alternative ways. Each is capable of generating conditions for open-ended evolution, but vary in their ability to do so. We find that state-dependent dynamics, regarded as a hallmark of life, statistically out-performs other candidate mechanisms, and is the only mechanism to produce open-ended evolution in a scalable manner, essential to the notion of ongoing evolution. This analysis suggests a new framework for unifying mechanisms for generating OEE with features distinctive to life and its artifacts, with broad applicability to biological and artificial systems.
Combination of High-density Microelectrode Array and Patch Clamp Recordings to Enable Studies of Multisynaptic Integration
Authors: Jäckel David , Bakkum Douglas J. , Russell Thomas L. , Müller Jan , Radivojevic Milos , Frey Urs , Franke Felix , Hierlemann Andreas
Published: April 2017

We present a novel, all-electric approach to record and to precisely control the activity of tens of individual presynaptic neurons. The method allows for parallel mapping of the efficacy of multiple synapses and of the resulting dynamics of postsynaptic neurons in a cortical culture. For the measurements, we combine an extracellular high-density microelectrode array, featuring 11’000 electrodes for extracellular recording and stimulation, with intracellular patch-clamp recording. We are able to identify the contributions of individual presynaptic neurons - including inhibitory and excitatory synaptic inputs - to postsynaptic potentials, which enables us to study dendritic integration. Since the electrical stimuli can be controlled at microsecond resolution, our method enables to evoke action potentials at tens of presynaptic cells in precisely orchestrated sequences of high reliability and minimum jitter. We demonstrate the potential of this method by evoking short- and long-term synaptic plasticity through manipulation of multiple synaptic inputs to a specific neuron.
The prognostic significance of Cdc6 and Cdt1 in breast cancer
Authors: Mahadevappa Ravikiran , Neves Henrique , Yuen Shun Ming , Bai Yuchen , McCrudden Cian M. , Yuen Hiu Fung , Wen Qing , Zhang Shu Dong , Kwok Hang Fai
Published: April 2017

DNA replication is a critical step in cell proliferation. Overexpression of MCM2-7 genes correlated with poor prognosis in breast cancer patients. However, the roles of Cdc6 and Cdt1, which work with MCMs to regulate DNA replication, in breast cancers are largely unknown. In the present study, we have shown that the expression levels of Cdc6 and Cdt1 were both significantly correlated with an increasing number of MCM2-7 genes overexpression. Both Cdc6 and Cdt1, when expressed in a high level, alone or in combination, were significantly associated with poorer survival in the breast cancer patient cohort (n = 1441). In line with this finding, the expression of Cdc6 and Cdt1 was upregulated in breast cancer cells compared to normal breast epithelial cells. Expression of Cdc6 and Cdt1 was significantly higher in ER negative breast cancer, and was suppressed when ER signalling was inhibited either by tamoxifen in vitro or letrozole in human subjects. Importantly, breast cancer patients who responded to letrozole expressed significantly lower Cdc6 than those patients who did not respond. Our results suggest that Cdc6 is a potential prognostic marker and therapeutic target in breast cancer patients.
Poly-protein G-expressing bacteria enhance the sensitivity of immunoassays
Authors: Hao Wen-Rui , Chen Michael , Chen Yi-Jou , Su Yu-Cheng , Cheng Chiu-Min , Hsueh Hsiang-Yin , Kao An-Pei , Hsieh Yuan-Chin , Chang Johny , Tseng Ming-Yang , Chuang Kuo-Hsiang
Published: April 2017

The sensitivities of solid-phase immunoassays are limited by the quantity of detection antibodies bound to their antigens on the solid phase. Here, we developed a poly-protein G-expressing bacterium as an antibody-trapping microparticle to enhance the signals of immunoassays by increasing the accumulation of detection antibodies on the given antigen. Eight tandemly repeated fragment crystallisable (Fc) binding domains of protein G were stably expressed on the surface of Escherichia coli BL21 cells (termed BL21/8G). BL21/8G cells showed a higher avidity for trapping antibodies on their surface than monomeric protein G-expressing BL21 (BL21/1G) cells did. In the sandwich enzyme-linked immunosorbent assay (ELISA), simply mixing the detection antibody with BL21/8G provided a detection limit of 6 pg/mL for human interferon-α (IFN-α) and a limit of 30 pg/mL for polyethylene glycol (PEG)-conjugated IFN-α (Pegasys), which are better than that of the traditional ELISA (30 pg/mL for IFN-α and 100 pg/mL for Pegasys). Moreover, the sensitivity of the Western blot for low-abundance Pegasys (0.4 ng/well) was increased by 25 folds upon mixing of an anti-PEG antibody with BL21/8G cells. By simply being mixed with a detection antibody, the poly-protein G-expressing bacteria can provide a new method to sensitively detect low-abundance target molecules in solid-phase immunoassays.
Low-noise time-resolved optical sensing of electromagnetic pulses from petawatt laser-matter interactions
Authors: Robinson T. S. , Consoli F. , Giltrap S. , Eardley S. J. , Hicks G. S. , Ditter E. J. , Ettlinger O. , Stuart N. H. , Notley M. , De Angelis R. , Najmudin Z. , Smith R. A.
Published: April 2017

We report on the development and deployment of an optical diagnostic for single-shot measurement of the electric-field components of electromagnetic pulses from high-intensity laser-matter interactions in a high-noise environment. The electro-optic Pockels effect in KDP crystals was used to measure transient electric fields using a geometry easily modifiable for magnetic field detection via Faraday rotation. Using dielectric sensors and an optical fibre-based readout ensures minimal field perturbations compared to conductive probes and greatly limits unwanted electrical pickup between probe and recording system. The device was tested at the Vulcan Petawatt facility with 1020 W cm−2 peak intensities, the first time such a diagnostic has been used in this regime. The probe crystals were located ~1.25 m from target and did not require direct view of the source plasma. The measured signals compare favourably with previously reported studies from Vulcan, in terms of the maximum measured intra-crystal field of 10.9 kV/m, signal duration and detected frequency content which was found to match the interaction chamber’s horizontal-plane fundamental harmonics of 76 and 101 MHz. Methods for improving the diagnostic for future use are also discussed in detail. Orthogonal optical probes offer a low-noise alternative for direct simultaneous measurement of each vector field component.
Application of high resolution melting assay (HRM) to study temperature-dependent intraspecific competition in a pathogenic bacterium
Authors: Ashrafi Roghaieh , Bruneaux Matthieu , Sundberg Lotta-Riina , Pulkkinen Katja , Ketola Tarmo
Published: April 2017

Studies on species’ responses to climate change have focused largely on the direct effect of abiotic factors and in particular temperature, neglecting the effects of biotic interactions in determining the outcome of climate change projections. Many microbes rely on strong interference competition; hence the fitness of many pathogenic bacteria could be a function of both their growth properties and intraspecific competition. However, due to technical challenges in distinguishing and tracking individual strains, experimental evidence on intraspecific competition has been limited so far. Here, we developed a robust application of the high-resolution melting (HRM) assay to study head-to-head competition between mixed genotype co-cultures of a waterborne bacterial pathogen of fish, Flavobacterium columnare, at two different temperatures. We found that competition outcome in liquid cultures seemed to be well predicted by growth yield of isolated strains, but was mostly inconsistent with interference competition results measured in inhibition tests on solid agar, especially as no growth inhibition between strain pairs was detected at the higher temperature. These results suggest that, for a given temperature, the factors driving competition outcome differ between liquid and solid environments.
C1QBP suppresses cell adhesion and metastasis of renal carcinoma cells
Authors: Wang Yong , Fu Donghe , Su Jing , Chen Yajing , Qi Can , Sun Yin , Niu Yuanjie , Zhang Ning , Yue Dan
Published: April 2017

Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein and can be upregulated or activated in a variety of malignant tumors, including those from thyroid, colon and breast, but its role remains unclear in renal cell carcinoma (RCC). In this study, C1QBP knockdown in RCC cell influenced expression of multiple genes associated with cell adhesion, among which L1 cell adhesion molecule (L1CAM) was significantly higher upon a reduction of C1QBP. In turn, cell adhesion and invasion abilities were significantly increased with increased metastasis to lung and liver in vivo. C1QBP may regulate RCC cell adhesion and invasion through influencing the p-GSK3/β-Catenin/L1CAM expression. Over all, our study demonstrated that C1QBP could regulate RCC metastasis by regulating the GSK3/β-Catenin/L1CAM signaling pathway.
Transcription Factor Antagonism Controls Enteroendocrine Cell Specification from Intestinal Stem Cells
Authors: Li Yumei , Pang Zhimin , Huang Huanwei , Wang Chenhui , Cai Tao , Xi Rongwen
Published: April 2017

The balanced maintenance and differentiation of local stem cells is required for Homeostatic renewal of tissues. In the Drosophila midgut, the transcription factor Escargot (Esg) maintains undifferentiated states in intestinal stem cells, whereas the transcription factors Scute (Sc) and Prospero (Pros) promote enteroendocrine cell specification. However, the mechanism through which Esg and Sc/Pros coordinately regulate stem cell differentiation is unknown. Here, by combining chromatin immunoprecipitation analysis with genetic studies, we show that both Esg and Sc bind to a common promoter region of pros. Moreover, antagonistic activity between Esg and Sc controls the expression status of Pros in stem cells, thereby, specifying whether stem cells remain undifferentiated or commit to enteroendocrine cell differentiation. Our study therefore reveals transcription factor antagonism between Esg and Sc as a novel mechanism that underlies fate specification from intestinal stem cells in Drosophila.
The yeast osmostress response is carbon source dependent
Authors: Babazadeh Roja , Lahtvee Petri-Jaan , Adiels Caroline B. , Goksör Mattias , Nielsen Jens B. , Hohmann Stefan
Published: April 2017

Adaptation to altered osmotic conditions is a fundamental property of living cells and has been studied in detail in the yeast Saccharomyces cerevisiae. Yeast cells accumulate glycerol as compatible solute, controlled at different levels by the High Osmolarity Glycerol (HOG) response pathway. Up to now, essentially all osmostress studies in yeast have been performed with glucose as carbon and energy source, which is metabolised by glycolysis with glycerol as a by-product. Here we investigated the response of yeast to osmotic stress when yeast is respiring ethanol as carbon and energy source. Remarkably, yeast cells do not accumulate glycerol under these conditions and it appears that trehalose may partly take over the role as compatible solute. The HOG pathway is activated in very much the same way as during growth on glucose and is also required for osmotic adaptation. Slower volume recovery was observed in ethanol-grown cells as compared to glucose-grown cells. Dependence on key regulators as well as the global gene expression profile were similar in many ways to those previously observed in glucose-grown cells. However, there are indications that cells re-arrange redox-metabolism when respiration is hampered under osmostress, a feature that could not be observed in glucose-grown cells.
Nanometre-scale 3D defects in Cr2AlC thin films
Authors: Chen Y. T. , Music D. , Shang L. , Mayer J. , Schneider J. M.
Published: April 2017

MAX-phase Cr2AlC containing thin films were synthesized by magnetron sputtering in an industrial system. Nanometre-scale 3D defects are observed near the boundary between regions of Cr2AlC and of the disordered solid solution (CrAl)xCy. Shrinkage of the Cr-Cr interplanar distance and elongation of the Cr-Al distance in the vicinity of the defects are detected using transmission electron microscopy. The here observed deformation surrounding the defects was described using density functional theory by comparing the DOS of bulk Cr2AlC with the DOS of a strained and unstrained Cr2AlC(0001) surface. From the partial density of states analysis, it can be learned that Cr-C bonds are stronger than Cr-Al bonds in bulk Cr2AlC. Upon Cr2AlC(0001) surface formation, both bonds are weakened. While the Cr-C bonds recover their bulk strength as Cr2AlC(0001) is strained, the Cr-Al bonds experience only a partial recovery, still being weaker than their bulk counterparts. Hence, the strain induced bond strengthening in Cr2AlC(0001) is larger for Cr d – C p bonds than for Cr d – Al p bonds. The here observed changes in bonding due to the formation of a strained surface are consistent with the experimentally observed elongation of the Cr-Al distance in the vicinity of nm-scale 3D defects in Cr2AlC thin films.
Sperm whale long-range echolocation sounds revealed by ANTARES, a deep-sea neutrino telescope
Authors: André M. , Caballé A. , van der Schaar M. , Solsona A. , Houégnigan L. , Zaugg S. , Sánchez A. M. , Castell J. V. , Solé M. , Vila F. , Djokic D. , Adrián-Martínez S. , Albert A. , Anghinolfi M. , Anton G. , Ardid M. , Aubert J.-J. , Avgitas T. , Baret B. , Barrios-Martí J. , Basa S. , Bertin V. , Biagi S. , Bormuth R. , Bouwhuis M. C. , Bruijn R. , Brunner J. , Busto J. , Capone A. , Caramete L. , Carr J. , Celli S. , Chiarusi T. , Circella M. , Coleiro A. , Coniglione R. , Costantini H. , Coyle P. , Creusot A. , Deschamps A. , De Bonis G. , Distefano C. , Di Palma I. , Donzaud C. , Dornic D. , Drouhin D. , Eberl T. , El Bojaddaini I. , Elsässer D. , Enzenhöfer A. , Fehn K. , Felis I. , Fusco L. A. , Galatà S. , Gay P. , Geißelsöder S. , Geyer K. , Giordano V. , Gleixner A. , Glotin H. , Gracia-Ruiz R. , Graf K. , Hallmann S. , van Haren H. , Heijboer A. J. , Hello Y. , Hernandez-Rey J. J. , Hößl J. , Hofestädt J. , Hugon C. , Illuminati G. , James C. W. , de Jong M. , Jongen M. , Kadler M. , Kalekin O. , Katz U. , Kießling D. , Kouchner A. , Kreter M. , Kreykenbohm I. , Kulikovskiy V. , Lachaud C. , Lahmann R. , Lefèvre D. , Leonora E. , Loucatos S. , Marcelin M. , Margiotta A. , Marinelli A. , Martínez-Mora J. A. , Mathieu A. , Melis K. , Michael T. , Migliozzi P. , Moussa A. , Mueller C. , Nezri E. , Păvălaş G. E. , Pellegrino C. , Perrina C. , Piattelli P. , Popa V. , Pradier T. , Racca C. , Riccobene G. , Roensch K. , Saldaña M. , Samtleben D. F. E. , Sanguineti M. , Sapienza P. , Schnabel J. , Schüssler F. , Seitz T. , Sieger C. , Spurio M. , Stolarczyk Th. , Sánchez-Losa A. , Taiuti M. , Trovato A. , Tselengidou M. , Turpin D. , Tönnis C. , Vallage B. , Vallée C. , Van Elewyck V. , Vivolo D. , Wagner S. , Wilms J. , Zornoza J. D. , Zuñiga J.
Published: April 2017

Despite dedicated research has been carried out to adequately map the distribution of the sperm whale in the Mediterranean Sea, unlike other regions of the world, the species population status is still presently uncertain. The analysis of two years of continuous acoustic data provided by the ANTARES neutrino telescope revealed the year-round presence of sperm whales in the Ligurian Sea, probably associated with the availability of cephalopods in the region. The presence of the Ligurian Sea sperm whales was demonstrated through the real-time analysis of audio data streamed from a cabled-to-shore deep-sea observatory that allowed the hourly tracking of their long-range echolocation behaviour on the Internet. Interestingly, the same acoustic analysis indicated that the occurrence of surface shipping noise would apparently not condition the foraging behaviour of the sperm whale in the area, since shipping noise was almost always present when sperm whales were acoustically detected. The continuous presence of the sperm whale in the region confirms the ecological value of the Ligurian sea and the importance of ANTARES to help monitoring its ecosystems.
Molecular evolutionary mechanisms driving functional diversification of α-glucosidase in Lepidoptera
Authors: Li Xiaotong , Shi Liangen , Zhou Yanyan , Xie Hongqing , Dai Xiangping , Li Rongqiao , Chen Yuyin , Wang Huabing
Published: April 2017

The digestive tract of lepidopteran insects is unique given its highly alkaline pH. The adaptive plasticity of digestive enzymes in this environment is crucial to the highly-efficient nutritional absorption in Lepidoptera. However, little is known about the molecular adaptation of digestive enzymes to this environment. Here, we show that lepidopteran α-glucosidase, a pivotal digestive enzyme, diverged into sucrose hydrolase (SUH) and other maltase subfamilies. SUH, which is specific for sucrose, was only detected in Lepidoptera. It suggests that lepidopteran insects have evolved an enhanced ability to hydrolyse sucrose, their major energy source. Gene duplications and exon-shuffling produced multiple copies of α-glucosidase in different microsyntenic regions. Furthermore, SUH showed significant functional divergence (FD) compared with maltase, which was affected by positive selection at specific lineages and codons. Nine sites, which were involved in both FD and positive selection, were located around the ligand-binding groove of SUH. These sites could be responsible for the ligand-binding preference and hydrolytic specificity of SUH for sucrose, and contribute to its conformational stability. Overall, our study demonstrated that positive selection is an important evolutionary force for the adaptive diversification of α-glucosidase, and for the exclusive presence of membrane-associated SUHs in the unique lepidopteran digestive tract.
Impact of metric and sample size on determining malaria hotspot boundaries
Authors: Stresman Gillian H. , Giorgi Emanuele , Baidjoe Amrish , Knight Phil , Odongo Wycliffe , Owaga Chrispin , Shagari Shehu , Makori Euniah , Stevenson Jennifer , Drakeley Chris , Cox Jonathan , Bousema Teun , Diggle Peter J.
Published: April 2017

The spatial heterogeneity of malaria suggests that interventions may be targeted for maximum impact. It is unclear to what extent different metrics lead to consistent delineation of hotspot boundaries. Using data from a large community-based malaria survey in the western Kenyan highlands, we assessed the agreement between a model-based geostatistical (MBG) approach to detect hotspots using Plasmodium falciparum parasite prevalence and serological evidence for exposure. Malaria transmission was widespread and highly heterogeneous with one third of the total population living in hotspots regardless of metric tested. Moderate agreement (Kappa = 0.424) was observed between hotspots defined based on parasite prevalence by polymerase chain reaction (PCR)- and the prevalence of antibodies to two P. falciparum antigens (MSP-1, AMA-1). While numerous biologically plausible hotspots were identified, their detection strongly relied on the proportion of the population sampled. When only 3% of the population was sampled, no PCR derived hotspots were reliably detected and at least 21% of the population was needed for reliable results. Similar results were observed for hotspots of seroprevalence. Hotspot boundaries are driven by the malaria diagnostic and sample size used to inform the model. These findings warn against the simplistic use of spatial analysis on available data to target malaria interventions in areas where hotspot boundaries are uncertain.
Correction: Corrigendum: Fluorescence-tunable Ag-DNA biosensor with tailored cytotoxicity for live-cell applications
Authors: Bossert Nelli , de Bruin Donny , Götz Maria , Bouwmeester Dirk , Heinrich Doris
Published: April 2017

Scientific Reports 6: Article number: 37897; published online: 30 November 2016; updated: 12 April 2017 In the ‘Introduction’ and ‘Results and Discussion’ sections of this manuscript, the authors used 2 sequences that were previously published and cited already as references 35 and 44. To better reflect the use of these sequences within the Introduction:
Luminescent manganese-doped CsPbCl3 perovskite quantum dots
Authors: Lin Chun Che , Xu Kun Yuan , Wang Da , Meijerink Andries
Published: April 2017

Nanocrystalline cesium lead halide perovskites (CsPbX3, X = Cl, Br, and I) form an exciting new class of semiconductor materials showing quantum confinement. The emission color can be tuned over the full visible spectral region making them promising for light‒emitting applications. Further control over the optical and magnetic properties of quantum dots (QDs) can be achieved through doping of transition metal (TM) ions such as Mn2+or Co2+. Here we demonstrate how, following QD synthesis in the presence of a Mn‒precursor, dropwise addition of silicon tetrachloride (SiCl4) to the QDs in toluene results in the formation of Mn‒doped CsPbCl3QDs showing bright orange Mn2+emission around 600 nm. Evidence for successful doping is provided by excitation spectra of the Mn2+emission, with all features of the CsPbCl3QD absorption spectrum and a decrease of the 410 nm excitonic emission life time with increasing Mn‒concentration, giving evidence for enhanced exciton to Mn2+energy transfer. As a doping mechanism we propose a combination of surface etching and reconstruction and diffusion doping. The presently reported approach provides a promising avenue for doping TM ions into perovskites QDs enabling a wider control over optical and magnetic properties for this new class of QDs.
Stereopsis deficits in patients with schizophrenia in a Han Chinese population
Authors: Hui Li , Sen Xia Hai , Shu Tang An , Feng Zhou Yi , Zhong Yin Guang , Long Hu Xing , Dong Du Xiang , Tang Yong
Published: April 2017

Although cognitive and sensory deficits have been identified as a core feature of schizophrenia, only a small portion of visual sensorium has been explored. To date, studies on visual system of three-dimensional percepts based on two-dimensional information still are limited. This study is the first to examine the integrity of stereopsis of schizophrenia in a Han Chinese population, and to further investigate the correlation of stereopsis with clinical symptoms. 100 patients with schizophrenia and 80 healthy controls were recruited. We assessed stereoacuity using the Titmus Stereopsis Test and clinical symptoms using Chinese versions of the Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS). There was a significant difference in log seconds of arc between two groups (p < 0.0001). The percentage of patients with correct stereopsis detection was significantly reduced at 400, 200, 140, 100, 80, 60, 50, and 40 seconds of arc than healthy controls (all, p < 0.01). Log seconds of arc in patients was not correlated with total scores and subscores of SAPS and SANS (all, p > 0.05). Our findings support that patients with schizophrenia have a marked deficit of stereopsis in a Han Chinese population. However, clinical symptoms do not influence stereopsis of schizophrenia.
A 3D-engineered porous conduit for peripheral nerve repair
Authors: Tao Jie , Hu Yu , Wang Shujuan , Zhang Jiumeng , Liu Xuan , Gou Zhiyuan , Cheng Hao , Liu Qianqi , Zhang Qianqian , You Shenglan , Gou Maling
Published: April 2017

End-to-end neurorrhaphy is the most commonly used method for treating peripheral nerve injury. However, only 50% of patients can regain useful function after treating with neurorrhaphy. Here, we constructed a 3D-engineered porous conduit to promote the function recovery of the transected peripheral nerve after neurorrhaphy. The conduit that consisted of a gelatin cryogel was prepared by molding with 3D-printed moulds. Due to its porous structure and excellent mechanical properties, this conduit could be collapsed by the mechanical force and resumed its original shape after absorption of normal saline. This shape-memory property allowed a simply surgery process for installing the conduits. Moreover, the biodegradable conduit could prevent the infiltration of fibroblasts and reduce the risk of scar tissue, which could provide an advantageous environment for nerve regeneration. The efficiency of the conduits in assisting peripheral nerve regeneration after neurorrhaphy was evaluated in a rat sciatic nerve transected model. Results indicated that conduits significantly benefitted the recovery of the transected peripheral nerve after end-to-end neurorrhaphy on the static sciatic index (SSI), electrophysiological results and the re-innervation of the gastrocnemius muscle. This work demonstrates a biodegradable nerve conduit that has potentially clinical application in promoting the neurorrhaphy.
Mutations in PMR1 stimulate xylose isomerase activity and anaerobic growth on xylose of engineered Saccharomyces cerevisiae by influencing manganese homeostasis
Authors: Verhoeven Maarten D. , Lee Misun , Kamoen Lycka , van den Broek Marcel , Janssen Dick B. , Daran Jean-Marc G. , van Maris Antonius J. A. , Pronk Jack T.
Published: April 2017

Combined overexpression of xylulokinase, pentose-phosphate-pathway enzymes and a heterologous xylose isomerase (XI) is required but insufficient for anaerobic growth of Saccharomyces cerevisiae on d-xylose. Single-step Cas9-assisted implementation of these modifications yielded a yeast strain expressing Piromyces XI that showed fast aerobic growth on d-xylose. However, anaerobic growth required a 12-day adaptation period. Xylose-adapted cultures carried mutations in PMR1, encoding a Golgi Ca2+/Mn2+ ATPase. Deleting PMR1 in the parental XI-expressing strain enabled instantaneous anaerobic growth on d-xylose. In pmr1 strains, intracellular Mn2+ concentrations were much higher than in the parental strain. XI activity assays in cell extracts and reconstitution experiments with purified XI apoenzyme showed superior enzyme kinetics with Mn2+ relative to other divalent metal ions. This study indicates engineering of metal homeostasis as a relevant approach for optimization of metabolic pathways involving metal-dependent enzymes. Specifically, it identifies metal interactions of heterologous XIs as an underexplored aspect of engineering xylose metabolism in yeast.
A Study on Fast Gates for Large-Scale Quantum Simulation with Trapped Ions
Authors: Taylor Richard L. , Bentley Christopher D. B. , Pedernales Julen S. , Lamata Lucas , Solano Enrique , Carvalho André R. R. , Hope Joseph J.
Published: April 2017

Large-scale digital quantum simulations require thousands of fundamental entangling gates to construct the simulated dynamics. Despite success in a variety of small-scale simulations, quantum information processing platforms have hitherto failed to demonstrate the combination of precise control and scalability required to systematically outmatch classical simulators. We analyse how fast gates could enable trapped-ion quantum processors to achieve the requisite scalability to outperform classical computers without error correction. We analyze the performance of a large-scale digital simulator, and find that fidelity of around 70% is realizable for π-pulse infidelities below 10−5 in traps subject to realistic rates of heating and dephasing. This scalability relies on fast gates: entangling gates faster than the trap period.
Bone Marrow Adipose Tissue Deficiency Increases Disuse-Induced Bone Loss in Male Mice
Authors: Keune Jessica A. , Wong Carmen P. , Branscum Adam J. , Iwaniec Urszula T. , Turner Russell T.
Published: April 2017

Bone marrow adipose tissue (MAT) is negatively associated with bone mass. Since osteoblasts and adipocytes are derived from the same precursor cells, adipocyte differentiation may occur at the expense of osteoblast differentiation. We used MAT-deficient KitW/W−v (MAT-) mice to determine if absence of MAT reduced bone loss in hindlimb-unloaded (HU) mice. Male MAT- and wild-type (WT) mice were randomly assigned to a baseline, control or HU group (n = 10 mice/group) within each genotype and HU groups unloaded for 2 weeks. Femurs were evaluated using micro-computed tomography, histomorphometry and targeted gene profiling. MAT- mice had a greater reduction in bone volume fraction after HU than did WT mice. HU MAT- mice had elevated cancellous bone formation and resorption compared to other treatment groups as well as a unique profile of differentially expressed genes. Adoptive transfer of WT bone marrow-derived hematopoietic stem cells reconstituted c-kit but not MAT in KitW/W−v mice. The MAT- WT → KitW/W−v mice lost cancellous bone following 2 weeks of HU. In summary, results from this study suggest that MAT deficiency was not protective, and was associated with exaggerated disuse-induced cancellous bone loss.
Performances of the hybrid between CyCa nucleocytplasmic hybrid fish and scattered mirror carp in different culture environments
Authors: Liu Xiangjiang , Liang Hongwei , Li Zhong , Liang Yongjun , Lu Cuiyun , Li Chitao , Chang Yumei , Zou Guiwei , Hu Guangfu
Published: April 2017

To improve the performance of growth traits and survival in common carp, CyCa nucleocytoplasmic hybrid fish (C) was used as parental fish for hybridization with Russian scattered mirror carp (R). Performances in morphological characters, growth traits and survival rate were compared among the purebreds (CC & RR) and crossbreds (RC & CR) at different time period in solitary and communal rearing system, respectively. The results demonstrated that both RC and CR crossbreds inherited the grey skin color type from the mirror carp, and got the full-scale pattern from the CyCa nucleocytoplasmic hybrid fish, which suggested that the grey color dominated to red color and full-scale dominated to scattered scale. With respect to yield, the RC crossbreds perform quite great compared to the RR and CC purebreds because they have quite high growth and survival rate. In contrast to RC crossbreds, the CR crossbreds performed poorly in growth traits, together with that crosses where scattered mirror carp was used as mother (RC and RR) achieved the greatest performance for all growth traits, suggested that the maternal influence also displayed an important role in growth traits. These results indicated that the RC crossbreds will be a potential carp variety for commercial production.
Windscapes and olfactory foraging in a large carnivore
Authors: Togunov Ron R. , Derocher Andrew E. , Lunn Nicholas J.
Published: April 2017

The theoretical optimal olfactory search strategy is to move cross-wind. Empirical evidence supporting wind-associated directionality among carnivores, however, is sparse. We examined satellite-linked telemetry movement data of adult female polar bears (Ursus maritimus) from Hudson Bay, Canada, in relation to modelled winds, in an effort to understand olfactory search for prey. In our results, the predicted cross-wind movement occurred most frequently at night during winter, the time when most hunting occurs, while downwind movement dominated during fast winds, which impede olfaction. Migration during sea ice freeze-up and break-up was also correlated with wind. A lack of orientation during summer, a period with few food resources, likely reflected reduced cross-wind search. Our findings represent the first quantitative description of anemotaxis, orientation to wind, for cross-wind search in a large carnivore. The methods are widely applicable to olfactory predators and their prey. We suggest windscapes be included as a habitat feature in habitat selection models for olfactory animals when evaluating what is considered available habitat.
Pressure-induced structural and spin transitions of Fe3S4
Authors: Huang Shengxuan , Kang Duan , Wu Xiang , Niu Jingjing , Qin Shan
Published: April 2017

Greigite (Fe3S4), isostructural with Fe3O4 has recently attracted great scientific interests from material science to geology due to its complicated structure and electronic and magnetic configurations. Here, an investigation into the structural, magnetic and electronic properties of Fe3S4 under high pressure has been conducted by first-principle calculations based on density functional theory. The results show that a first-order phase transition of Fe3S4 would occur from the inverse spinel (SP) structure to the Cr3S4-type (CS) structure at 3.4 GPa, accompanied by a collapse of 9.7% in the volume, a redistribution of iron cations, and a half-metal to metal transition. In the CS-Fe3S4, Fe2+ located at octahedral environment firstly undergoes a transition from high-spin (HS) state to low-spin (LS) state at 8.5 GPa and Fe3+ subsequently does at 17 GPa. The Equation of State for different phases of Fe3S4 are also determined. Our results not only give some clues to explore novel materials by utilizing Fe3S4 but also shed light on the fundamental information of Fe3O4, as well as those of other SP-AB2X4 compounds.
Characterization of c-Maf+Foxp3− Regulatory T Cells Induced by Repeated Stimulation of Antigen-Presenting B Cells
Authors: Chien Chien-Hui , Yu Hui-Chieh , Chen Szu-Ying , Chiang Bor-Luen
Published: April 2017

The role of B cells in the development of CD4+regulatory T cells has been emphasized recently. Our previous studies have demonstrated that the antigen-presenting splenic B cells converted naïve CD4+CD25−T cells into CD4+CD25+Foxp3−T cells without additional cytokines or chemicals with regulatory activity and that referred to as Treg-of-B cells. The present study further showed that Treg-of-B cells increased the IL-10-producing population, and the expression of c-Maf, inducible T-cell co-stimulator (ICOS) as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) after repeated stimulation of B cells in a cell-cell contact-dependent manner. Long-term cultured Treg-of-B cells exerted IL-10 and CTLA4-mediated antigen-specific suppressive activity; moreover, the single antigen-specific Treg-of-B cells inhibited in a non-antigen-specific fashion. In conclusion, these results suggest that repeated stimulation of B cells induced IL-10-producing CD4+Foxp3−regulatory T cells in a contact-dependent manner and these Treg-of-B cells possess IL-10 and CTLA4-dependent suppressive function.
Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer’s disease-like tau pathology
Authors: Gratuze Maud , Julien Jacinthe , Petry Franck R. , Morin Françoise , Planel Emmanuel
Published: April 2017

Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer’s disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insulin dysfunction affect tau pathology, is not well understood. In this study, we examined the effects of insulin deficiency on tau pathology in transgenic hTau mice by injecting different doses of streptozotocin (STZ), a toxin that destroys insulin-producing cells in the pancreas. One high dose of STZ resulted in marked diabetes, and five low doses led to a milder diabetes. Both groups exhibited brain tau hyperphosphorylation but no increased aggregation. Tau hyperphosphorylation correlated with inhibition of Protein Phosphatase 2A (PP2A), the main tau phosphatase. Interestingly, insulin injection 30 minutes before sacrifice partially restored tau phosphorylation to control levels in both STZ-injected groups. Our results confirm a link between insulin homeostasis and tau phosphorylation, which could explain, at least in part, a higher incidence of AD in diabetic patients.
Injection-modulated polarity conversion by charge carrier density control via a self-assembled monolayer for all-solution-processed organic field-effect transistors
Authors: Roh Jeongkyun , Lee Taesoo , Kang Chan-mo , Kwak Jeonghun , Lang Philippe , Horowitz Gilles , Kim Hyeok , Lee Changhee
Published: April 2017

We demonstrated modulation of charge carrier densities in all-solution-processed organic field-effect transistors (OFETs) by modifying the injection properties with self-assembled monolayers (SAMs). The all-solution-processed OFETs based on an n-type polymer with inkjet-printed Ag electrodes were fabricated as a test platform, and the injection properties were modified by the SAMs. Two types of SAMs with different dipole direction, thiophenol (TP) and pentafluorobenzene thiol (PFBT) were employed, modifying the work function of the inkjet-printed Ag (4.9 eV) to 4.66 eV and 5.24 eV with TP and PFBT treatments, respectively. The charge carrier densities were controlled by the SAM treatment in both dominant and non-dominant carrier-channel regimes. This work demonstrates that control of the charge carrier densities can be efficiently achieved by modifying the injection property with SAM treatment; thus, this approach can achieve polarity conversion of the OFETs.
Protective efficacy of Zika vaccine in AG129 mouse model
Authors: Sumathy K. , Kulkarni Bharathi , Gondu Ravi Kumar , Ponnuru Sampath Kumar , Bonguram Nagaraju , Eligeti Rakesh , Gadiyaram Sindhuja , Praturi Usha , Chougule Bhushan , Karunakaran Latha , Ella Krishna M.
Published: April 2017

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes asymptomatic infection or presents only mild symptoms in majority of those infected. However, vaccination for ZIKV is a public health priority due to serious congenital and neuropathological abnormalities observed as a sequelae of the virus infection in the recent epidemics. We have developed an inactivated virus vaccine with the African MR 766 strain. Here we show that two doses of the vaccine provided 100% efficacy against mortality and disease following challenge with homotypic MR 766 and the heterotypic FSS 13025 ZIKV strains in the Type I and Type II interferon deficient AG129 mice. Two doses of the vaccine elicited high titer of neutralizing antibodies in Balb/c mice, and the vaccine antisera conferred protection against virus challenge in passively immunized mice. The studies were useful to rationalize vaccine doses for protective efficacy. Furthermore, the vaccine antisera neutralized the homotypic and heterotypic ZIKV strains in vitro with equivalent efficiency. Our study suggests a single ZIKV serotype, and that the development of an effective vaccine may not be limited by the choice of virus strain.
Development and validation of a method for precise dating of female puberty in laboratory rodents: The puberty ovarian maturation score (Pub-Score)
Authors: Gaytan Francisco , Morales Concepción , Leon Silvia , Heras Violeta , Barroso Alexia , Avendaño Maria S. , Vazquez Maria J. , Castellano Juan M. , Roa Juan , Tena-Sempere Manuel
Published: April 2017

Puberty is a key developmental event whose primary regulatory mechanisms remain poorly understood. Precise dating of puberty is crucial for experimental (preclinical) studies on its complex neuroendocrine controlling networks. In female laboratory rodents, external signs of puberty, such as vaginal opening (VO) and epithelial cell cornification (i.e., first vaginal estrus, FE), are indirectly related to the maturational state of the ovary and first ovulation, which is the unequivocal marker of puberty. Whereas in rats, VO and FE are almost simultaneous with the first ovulation, these events are not so closely associated in mice. Moreover, external signs of puberty can be uncoupled with first ovulation in both species under certain experimental conditions. We propose herein the Pubertal Ovarian Maturation Score (Pub-score), as novel, reliable method to assess peripubertal ovarian maturation in rats and mice. This method is founded on histological evaluation of pre-pubertal ovarian maturation, based on antral follicle development, and the precise timing of first ovulation, by retrospective dating of maturational and regressive changes in corpora lutea. This approach allows exact timing of puberty within a time-window of at least two weeks after VO in both species, thus facilitating the identification and precise dating of advanced or delayed puberty under various experimental conditions.
Quantum-Dot Light-Emitting Diodes with Nitrogen-Doped Carbon Nanodot Hole Transport and Electronic Energy Transfer Layer
Authors: Park Young Ran , Jeong Hu Young , Seo Young Soo , Choi Won Kook , Hong Young Joon
Published: April 2017

Electroluminescence efficiency is crucial for the application of quantum-dot light-emitting diodes (QD-LEDs) in practical devices. We demonstrate that nitrogen-doped carbon nanodot (N-CD) interlayer improves electrical and luminescent properties of QD-LEDs. The N-CDs were prepared by solution-based bottom up synthesis and were inserted as a hole transport layer (HTL) between other multilayer HTL heterojunction and the red-QD layer. The QD-LEDs with N-CD interlayer represented superior electrical rectification and electroluminescent efficiency than those without the N-CD interlayer. The insertion of N-CD layer was found to provoke the Förster resonance energy transfer (FRET) from N-CD to QD layer, as confirmed by time-integrated and -resolved photoluminescence spectroscopy. Moreover, hole-only devices (HODs) with N-CD interlayer presented high hole transport capability, and ultraviolet photoelectron spectroscopy also revealed that the N-CD interlayer reduced the highest hole barrier height. Thus, more balanced carrier injection with sufficient hole carrier transport feasibly lead to the superior electrical and electroluminescent properties of the QD-LEDs with N-CD interlayer. We further studied effect of N-CD interlayer thickness on electrical and luminescent performances for high-brightness QD-LEDs. The ability of the N-CD interlayer to improve both the electrical and luminescent characteristics of the QD-LEDs would be readily exploited as an emerging photoactive material for high-efficiency optoelectronic devices.
Regulation of miR163 and its targets in defense against Pseudomonas syringae in Arabidopsis thaliana
Authors: Chow Hiu Tung , Ng Danny W-K.
Published: April 2017

Small RNAs are important regulators for a variety of biological processes, including leaf development, flowering-time, embryogenesis and defense responses. miR163 is a non-conserved miRNA and its locus has evolved recently through inverted duplication of its target genes to which they belong to the SABATH family of related small-molecule methyltransferases (MTs). In Arabidopsis thaliana, previous study demonstrated that miR163 accumulation was induced by alamethicin treatment, suggesting its roles in defense response pathways. Enhanced resistance against Pseudomonas syringae pv. tomato (Pst) was observed in the mir163 mutant, whereas transgenic lines overexpressing miR163 showed increase sensitivity to Pst, suggesting that miR163 is a negative regulator of defense response. Elevated level of miR163 and its targets in A. thaliana were observed upon Pst treatment, suggesting a modulating relationship between miR163 and its targets. In addition, miR163 and histone deacetylase were found to act cooperatively in mediating defense against Pst. Transgenic plants overexpressing miR163-resistant targets suggested their different contributions in defense. Results from this study revealed that the stress-inducible miR163 and its targets act in concert to modulate defense responses against bacterial pathogen in A. thaliana.
The Prevalence of Depression and Depressive Symptoms among Eye Disease Patients: A Systematic Review and Meta-analysis
Authors: Zheng Yajing , Wu Xiaohang , Lin Xiaoming , Lin Haotian
Published: April 2017

The prevalence of depression among different eye disease patients varies across studies and has not been systematically reviewed. This study is to provide a summary of the prevalence of depression among eye disease patients. PubMed, Medline, Embase and Cochrane Library were searched from January, 1990 to December, 2015 to identify studies with information on the prevalence of depression among ophthalmic patients. A random/fixed-effects meta-analysis was used to estimate the pooled prevalence of depression among eye disease patients. Heterogeneity was assessed with the I2 test. 28 studies were selected from 3162 references. The overall pooled prevalence of depression or depressive symptoms with eye disease was 25% (1502/6589 individuals, 95% CI, 0.20–0.30) ranging from 5.4% to 57.0%. Regarding different disease categories, the highest prevalence was revealed for dry eye disease (DED) with 29%, followed by 25% for glaucoma patients, 24% for age-related macular degeneration (AMD) patients, 23% for cataract patients. The increased pooled prevalence of depression was identified in those with eye diseases compared with healthy controls (OR, 1.59; 95% CI, 1.40–1.81; I2 = 68.5%). Substantial heterogeneity was identified across most estimates (I2 > 75%). Further research is needed to identify effective strategies for preventing and treating depression among eye disease patients.
Lignocellulose fermentation and residual solids characterization for senescent switchgrass fermentation by Clostridium thermocellum in the presence and absence of continuous in situ ball-milling
Authors: Balch Mikayla L. , Holwerda Evert K. , Davis Mark F. , Sykes Robert W. , Happs Renee M. , Kumar Rajeev , Wyman Charles E. , Lynd Lee R.
Published: April 2017

Milling during lignocellulosic fermentation, cotreatment, is investigated as an alternative to thermochemical pretreatment for biological processing of cellulosic biomass.
Evaluation of the DGT technique for selective measurement of aluminium and trace metal concentrations in an acid drainage-impacted coastal waterway
Authors: Shiva Amir Houshang , Teasdale Peter R. , Welsh David T. , Bennett William W.
Published: April 2017

DGT samplers with different binding layers (Chelex, Metsorb and mixed Chelex–Metsorb) were evaluated for measurement of Al and trace metals in four natural waters with a range of pH.
Dietary krill oil enhances neurocognitive functions and modulates proteomic changes in brain tissues of d-galactose induced aging mice
Authors: Cheong Ling-Zhi , Sun Tingting , Li Yanyan , Zhou Jun , Lu Chenyang , Li Ye , Huang Zhongbai , Su Xiurong
Published: April 2017

The effects of dietary krill oil on neurocognitive functions and proteomic changes in brain tissues of d-galactose-induced aging mice were evaluated.
Computer aided design and NMR characterization of an oligopeptide targeting the Ebola virus VP24 protein
Authors: Dapiaggi Federico , Pieraccini Stefano , Potenza Donatella , Vasile Francesca , Macut Helena , Pellegrino Sara , Aliverti Alessandro , Sironi Maurizio
Published: April 2017

The nona-peptide RS, designed on the basis of computational studies, is able to interact with Ebola VP24 and potentially inhibit its interaction with KPNA.
Restriction of telomerase capping by short non-toxic peptides via arresting telomeric G-quadruplex
Authors: Jana Jagannath , Sengupta Pallabi , Mondal Soma , Chatterjee Subhrangsu
Published: April 2017

The stabilization of a G-quadruplex structure in human telomeric DNA has become a promising strategy in the development of cancer therapeutics.