bluuebunny/crossref_metadata_2025 huggingface dataset:
The coincidence of ecological opportunity with hybridization explains rapid adaptive radiation in Lake Mweru cichlid fishes
Authors: Meier Joana I. , Stelkens Rike B. , Joyce Domino A. , Mwaiko Salome , Phiri Numel , Schliewen Ulrich K. , Selz Oliver M. , Wagner Catherine E. , Katongo Cyprian , Seehausen Ole
Published: December 2019

The process of adaptive radiation was classically hypothesized to require isolation of a lineage from its source (no gene flow) and from related species (no competition). Alternatively, hybridization between species may generate genetic variation that facilitates adaptive radiation. Here we study haplochromine cichlid assemblages in two African Great Lakes to test these hypotheses. Greater biotic isolation (fewer lineages) predicts fewer constraints by competition and hence more ecological opportunity in Lake Bangweulu, whereas opportunity for hybridization predicts increased genetic potential in Lake Mweru. In Lake Bangweulu, we find no evidence for hybridization but also no adaptive radiation. We show that the Bangweulu lineages also colonized Lake Mweru, where they hybridized with Congolese lineages and then underwent multiple adaptive radiations that are strikingly complementary in ecology and morphology. Our data suggest that the presence of several related lineages does not necessarily prevent adaptive radiation, although it constrains the trajectories of morphological diversification. It might instead facilitate adaptive radiation when hybridization generates genetic variation, without which radiation may start much later, progress more slowly or never occur.
An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment
Authors: Tekpli Xavier , Lien Tonje , Røssevold Andreas Hagen , Nebdal Daniel , Borgen Elin , Ohnstad Hege Oma , Kyte Jon Amund , Vallon-Christersson Johan , Fongaard Marie , Due Eldri Undlien , Svartdal Lisa Gregusson , Sveli My Anh Tu , Garred Øystein ,   OSBREAC, Børresen-Dale Anne-Lise , Schlichting Ellen , Sauer Torill , Geisler Jürgen , Hofvind Solveig , Bathen Tone F. , Engebråten Olav , Geitvik Gry Aarum , Langerød Anita , Kåresen Rolf , Mælandsmo Gunhild Mari , Lingjærde Ole Christian , Skjerven Helle Kristine , Park Daehoon , Fritzman Britt , Frigessi Arnoldo , Sahlberg Kristine Kleivi , Sørlie Therese , Russnes Hege G. , Naume Bjørn , Kristensen Vessela N.
Published: December 2019

How mixtures of immune cells associate with cancer cell phenotype and affect pathogenesis is still unclear. In 15 breast cancer gene expression datasets, we invariably identify three clusters of patients with gradual levels of immune infiltration. The intermediate immune infiltration cluster (Cluster B) is associated with a worse prognosis independently of known clinicopathological features. Furthermore, immune clusters are associated with response to neoadjuvant chemotherapy. In silico dissection of the immune contexture of the clusters identified Cluster A as immune cold, Cluster C as immune hot while Cluster B has a pro-tumorigenic immune infiltration. Through phenotypical analysis, we find epithelial mesenchymal transition and proliferation associated with the immune clusters and mutually exclusive in breast cancers. Here, we describe immune clusters which improve the prognostic accuracy of immune contexture in breast cancer. Our discovery of a novel independent prognostic factor in breast cancer highlights a correlation between tumor phenotype and immune contexture.
Multimodal image registration and connectivity analysis for integration of connectomic data from microscopy to MRI
Authors: Goubran Maged , Leuze Christoph , Hsueh Brian , Aswendt Markus , Ye Li , Tian Qiyuan , Cheng Michelle Y. , Crow Ailey , Steinberg Gary K. , McNab Jennifer A. , Deisseroth Karl , Zeineh Michael
Published: December 2019

3D histology, slice-based connectivity atlases, and diffusion MRI are common techniques to map brain wiring. While there are many modality-specific tools to process these data, there is a lack of integration across modalities. We develop an automated resource that combines histologically cleared volumes with connectivity atlases and MRI, enabling the analysis of histological features across multiple fiber tracts and networks, and their correlation within-vivobiomarkers. We apply our pipeline in a murine stroke model, demonstrating not only strong correspondence between MRI abnormalities and CLARITY-tissue staining, but also uncovering acute cellular effects in areas connected to the ischemic core. We provide improved maps of connectivity by quantifying projection terminals from CLARITY viral injections, and integrate diffusion MRI with CLARITY viral tracing to compare connectivity maps across scales. Finally, we demonstrate tract-level histological changes of stroke through this multimodal integration. This resource can propel investigations of network alterations underlying neurological disorders.
Using somatic variant richness to mine signals from rare variants in the cancer genome
Authors: Chakraborty Saptarshi , Arora Arshi , Begg Colin B. , Shen Ronglai
Published: December 2019

To date, the vast preponderance of somatic variants observed in the cancer genome have been rare variants, and it is common in practice to encounter in a new tumor variants that have not been observed previously. Here we focus on probability estimation for encountering such hitherto unseen variants. We draw upon statistical methodology that has been developed in other fields of study, notably in species estimation in ecology, and word frequency estimation in computational linguistics. Analysis of whole-exome and targeted panel sequencing data sets reveal substantial variability in variant “richness” between genes that could be harnessed for clinically relevant problems. We quantify the variant-tissue association and show a strong gene-specific, lineage-dependent pattern of encountering new variants. This variability is largely determined by the proportion of observed variants that are rare. Our findings suggest that variants that occur at very low frequencies can harbor important signals that are clinically consequential.
Single-spin qubits in isotopically enriched silicon at low magnetic field
Authors: Zhao R. , Tanttu T. , Tan K. Y. , Hensen B. , Chan K. W. , Hwang J. C. C. , Leon R. C. C. , Yang C. H. , Gilbert W. , Hudson F. E. , Itoh K. M. , Kiselev A. A. , Ladd T. D. , Morello A. , Laucht A. , Dzurak A. S.
Published: December 2019

Single-electron spin qubits employ magnetic fields on the order of 1 Tesla or above to enable quantum state readout via spin-dependent-tunnelling. This requires demanding microwave engineering for coherent spin resonance control, which limits the prospects for large scale multi-qubit systems. Alternatively, singlet-triplet readout enables high-fidelity spin-state measurements in much lower magnetic fields, without the need for reservoirs. Here, we demonstrate low-field operation of metal-oxide-silicon quantum dot qubits by combining coherent single-spin control with high-fidelity, single-shot, Pauli-spin-blockade-based ST readout. We discover that the qubits decohere faster at low magnetic fields with $${T}_{2}^{\,\text{Rabi}\,}=18.6$$T2Rabi=18.6 μs and $${T}_{2}^{* }=1.4$$T2*=1.4 μs at 150 mT. Their coherence is limited by spin flips of residual 29Si nuclei in the isotopically enriched 28Si host material, which occur more frequently at lower fields. Our finding indicates that new trade-offs will be required to ensure the frequency stabilization of spin qubits, and highlights the importance of isotopic enrichment of device substrates for the realization of a scalable silicon-based quantum processor.
Molecular engineering of organic semiconductors enables noble metal-comparable SERS enhancement and sensitivity
Authors: Demirel Gokhan , Gieseking Rebecca L. M. , Ozdemir Resul , Kahmann Simon , Loi Maria A. , Schatz George C. , Facchetti Antonio , Usta Hakan
Published: December 2019

Nanostructured molecular semiconductor films are promising Surface-Enhanced Raman Spectroscopy (SERS) platforms for both fundamental and technological research. Here, we report that a nanostructured film of the small molecule DFP-4T, consisting of a fully π-conjugated diperfluorophenyl-substituted quaterthiophene structure, demonstrates a very large Raman enhancement factor (>105) and a low limit of detection (10−9 M) for the methylene blue probe molecule. This data is comparable to those reported for the best inorganic semiconductor- and even intrinsic plasmonic metal-based SERS platforms. Photoluminescence spectroscopy and computational analysis suggest that both charge-transfer energy and effective molecular interactions, leading to a small but non-zero oscillator strength in the charge-transfer state between the organic semiconductor film and the analyte molecule, are required to achieve large SERS enhancement factors and high molecular sensitivities in these systems. Our results provide not only a considerable experimental advancement in organic SERS figure-of-merits but also a guidance for the molecular design of more sensitive SERS systems.
Strong spin resonance mode associated with suppression of soft magnetic ordering in hole-doped Ba1-xNaxFe2As2
Authors: Waßer Florian , Park Jitae T. , Aswartham Saicharan , Wurmehl Sabine , Sidis Yvan , Steffens Paul , Schmalzl Karin , Büchner Bernd , Braden Markus
Published: December 2019

Spin-resonance modes (SRM) are taken as evidence for magnetically driven pairing in Fe-based superconductors, but their character remains poorly understood. The broadness, the splitting and the spin-space anisotropies of SRMs contrast with the mostly accepted interpretation as spin excitons. We study hole-doped Ba1−xNaxFe2As2 that displays a spin reorientation transition. This reorientation has little impact on the overall appearance of the resonance excitations with a high-energy isotropic and a low-energy anisotropic mode. However, the strength of the anisotropic low-energy mode sharply peaks at the highest doping that still exhibits magnetic ordering resulting in the strongest SRM observed in any Fe-based superconductor so far. This remarkably strong SRM is accompanied by a loss of about half of the magnetic Bragg intensity upon entering the SC phase. Anisotropic SRMs thus can allow the system to compensate for the loss of exchange energy arising from the reduced antiferromagnetic correlations within the SC state.
Layer specificity of inputs from supplementary motor area and dorsal premotor cortex to primary motor cortex in macaque monkeys
Authors: Ninomiya Taihei , Inoue Ken-ichi , Hoshi Eiji , Takada Masahiko
Published: December 2019

The primate frontal lobe processes diverse motor information in parallel through multiple motor-related areas. For example, the supplementary motor area (SMA) is mainly involved in internally-triggered movements, whereas the premotor cortex (PM) is highly responsible for externally-guided movements. The primary motor cortex (M1) deals with both aspects of movements to execute a single motor behavior. To elucidate how the cortical motor system is structured to process a variety of information, the laminar distribution patterns of signals were examined between SMA and M1, or PM and M1 in macaque monkeys by using dual anterograde tract-tracing. Dense terminal labeling was observed in layers 1 and upper 2/3 of M1 after one tracer injection into SMA, another tracer injection into the dorsal division of PM resulted in prominent labeling in the deeper portion of layer 2/3. Weaker labeling was also visible in layer 5 in both cases. On the other hand, inputs from M1 terminated in both the superficial and the deep layers of SMA and PM. The present data indicate that distinct types of motor information are arranged in M1 in a layer-specific fashion to be orchestrated through a microcircuit within M1.
Practical Security Analysis of Reference Pulses for Continuous-Variable Quantum Key Distribution
Authors: Zhao Wei , Shi Ronghua , Huang Duan
Published: December 2019

By manipulating the reference pulses amplitude, a security vulnerability is caused by self-reference continuous-variable quantum key distribution. In this paper, we formalize an attack strategy for reference pulses, showing that the proposed attack can compromise the practical security of CVQKD protocol. In this scheme, before the beam splitter attack, Eve intercepts the reference pulses emitted by Alice, using Bayesian algorithm to estimate phase shifts. Subsequently, other reference pulses are re-prepared and resubmitted to Bob. In simulations, Bayesian algorithm effectively estimates the phase drifts and has the high robustness to noise. Therefore, the eavesdropper can bias the excess noise due to the intercept-resend attack and the beam splitter attack. And Alice and Bob believe that their excess noise is below the null key threshold and can still share a secret key. Consequently, the proposed attack shows that its practical security can be compromised by transmitting the reference pulses in the continuous-variable quantum key distribution protocol.
Actinomycin D and Telmisartan Combination Targets Lung Cancer Stem Cells Through the Wnt/Beta Catenin Pathway
Authors: Green Ryan , Howell Mark , Khalil Roukiah , Nair Rajesh , Yan Jiyu , Foran Elspeth , Katiri Sandhyabanu , Banerjee Jit , Singh Mandip , Bharadwaj Srinivas , Mohapatra Shyam S. , Mohapatra Subhra
Published: December 2019

The failure of lung cancer treatments has been attributed mostly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. Cancer initiating stem cells (CSCs), present in tumors in a small percentage, play critical roles in the development of drug resistance, metastasis, and cancer relapse. Hence, novel treatments targeting both bulk cancer cells and CSCs are under intense investigation. Herein, we report that lung cancer cells grown on a 3D fibrous scaffold form tumoroids that resemble in vivo tumors, expand CSCs, and provide a platform to identify anti-CSC drugs. The screening of an NCI library of FDA-approved drugs using tumoroid cultures led to identification of Actinomycin D (AD) as a top CSC inhibitor. Since CSCs are mostly resident in the tumor’s inner core, AD was combined with an angiotensin receptor antagonist, Telmisartan (TS), which is known to increase drug permeability in tumors and was shown to have anti-CSC activity. Our results showed that AD + TS administered intra-tumorally was significantly more effective than either drug alone in both syngeneic and xenograft mouse models. The results of mechanistic studies revealed that CSC expansion in tumoroids was associated with activation of β catenin signaling and that AD + TS treatment reduced active β catenin levels in tumors. Together, these results establish the utility of the tumoroid culture system to expand CSCs ex vivo for targeted drug screening, to identify promising novel treatments with both anti-CSC and anti-cancer effects, and to individualize treatments for metastatic drug resistant lung cancer patients.
Subendothelial stiffness alters endothelial cell traction force generation while exerting a minimal effect on the transcriptome
Authors: Bastounis Effie E. , Yeh Yi-Ting , Theriot Julie A.
Published: December 2019

Endothelial cells respond to changes in subendothelial stiffness by altering their migration and mechanics, but whether those responses are due to transcriptional reprogramming remains largely unknown. We measured traction force generation and also performed gene expression profiling for two endothelial cell types grown in monolayers on soft or stiff matrices: primary human umbilical vein endothelial cells (HUVEC) and immortalized human microvascular endothelial cells (HMEC-1). Both cell types respond to changes in subendothelial stiffness by increasing the traction stresses they exert on stiffer as compared to softer matrices, and exhibit a range of altered protein phosphorylation or protein conformational changes previously implicated in mechanotransduction. However, the transcriptome has only a minimal role in this conserved biomechanical response. Only few genes were differentially expressed in each cell type in a stiffness-dependent manner, and none were shared between them. In contrast, thousands of genes were differentially regulated in HUVEC as compared to HMEC-1. HUVEC (but not HMEC-1) upregulate expression of TGF-β2 on stiffer matrices, and also respond to application of exogenous TGF-β2 by enhancing their endogenous TGF-β2 expression and their cell-matrix traction stresses. Altogether, these findings provide insights into the relationship between subendothelial stiffness, endothelial mechanics and variation of the endothelial cell transcriptome, and reveal that subendothelial stiffness, while critically altering endothelial cells’ mechanical behavior, minimally affects their transcriptome.
Expressivity of the key genes associated with seed and pod development is highly regulated via lncRNAs and miRNAs in Pigeonpea
Authors: Das Antara , Nigam Deepti , Junaid Alim , Tribhuvan Kishor U. , Kumar Kuldeep , Durgesh Kumar , Singh N. K. , Gaikwad Kishor
Published: December 2019

Non-coding RNA’s like miRNA, lncRNA, have gained immense importance as a significant regulatory factor in different physiological and developmental processes in plants. In an effort to understand the molecular role of these regulatory agents, in the present study, 3019 lncRNAs and 227 miRNAs were identified from different seed and pod developmental stages in Pigeonpea, a major grain legume of Southeast Asia and Africa. Target analysis revealed that 3768 mRNAs, including 83 TFs were targeted by lncRNAs; whereas 3060 mRNA, including 154 TFs, were targeted by miRNAs. The targeted transcription factors majorly belong to WRKY, MYB, bHLH, etc. families; whereas the targeted genes were associated with the embryo, seed, and flower development. Total 302 lncRNAs interact with miRNAs and formed endogenous target mimics (eTMs) which leads to sequestering of the miRNAs present in the cell. Expression analysis showed that notably, Cc_lncRNA-2830 expression is up-regulated and sequestrates miR160h in pod leading to higher expression of the miR160h target gene, Auxin responsive factor-18. A similar pattern was observed for SPIKE, Auxin signaling F-box-2, Bidirectional sugar transporter, and Starch synthetase-2 eTMs. All the identified target mRNAs code for transcription factor and genes are involved in the processes like cell division, plant growth and development, starch synthesis, sugar transportation and accumulation of storage proteins which are essential for seed and pod development. On a combinatorial basis, our study provides a lncRNA and miRNA based regulatory insight into the genes governing seed and pod development in Pigeonpea.
Spontaneous categorization of tools based on observation in children and chimpanzees
Authors: Gruber Thibaud , Frick Aurélien , Hirata Satoshi , Adachi Ikuma , Biro Dora
Published: December 2019

The acquisition of the concept of ‘tool’ remains intriguing from both developmental and comparative perspectives. Our current model of tool use development in children is based on humans’ supposedly unique ability to adopt a teleological stance: the understanding of a demonstrator’s goal-based intentions when using a tool. It is however unclear how children and chimpanzees, our closest relatives, combine their knowledge of different objects whose function is to act on other parts of the environment, and assign them to a single category of ‘tools’. Here, we used a function-based approach to address this question. We exposed 7 to 11-year-old children and adult chimpanzees to a Matching-to-Function (MTF) task to explore whether they would sort tools and non-tools separately after demonstration of their function by an experimenter. MTF is a variant of Matching-to-Sample where the sample and the target are from the same category/kind rather than identical. Around 40% of children paired objects according to their function in the MTF task, with only one child younger than 8 years doing so. Moreover, when verbally questioned, these children offered a function-based answer to explain their choices. One of six chimpanzees also successfully paired objects according to function. Children and at least one chimpanzee can thus spontaneously sort tools into functional categories based on observing a demonstrator. The success of a single chimpanzee in our task suggests that teleological reasoning might already have been present in our last common ancestor but also shows that human children more readily conceptualize tools in a spontaneous fashion.
Drivers of bird-window collisions in southern South America: a two-scale assessment applying citizen science
Authors: Rebolo-Ifrán Natalia , di Virgilio Agustina , Lambertucci Sergio A.
Published: December 2019

Bird-window collisions are one of the main causes of avian mortality worldwide, with estimations reaching up to almost one billion of dead individuals annually due to this cause in Canada and the USA alone. Although this is a growing conservation problem, most of the studies come from North America, evidencing the lack of knowledge and concern in countries with high biodiversity and growing population development. Our objectives were: (1) to estimate the current situation of bird-window collisions in Argentina, a country with around 10% of the world’s avian biodiversity, and, (2) to identify drivers of bird-window collisions at a national and local scale, focusing on a city surrounded by a protected area. We used a citizen science project called “Bird-Window Collisions in Argentina” that consisted of an online survey that collected data on collision metrics and risk factors. We found that more than half of participants reported at least one collision during the last year, suggesting this issue is common and widespread. In addition, our data show that the number of windows and the presence of vegetation reflected in windows are factors that strongly influence the risk of collision at national scale. On the other hand, the environment surrounding buildings affects the rate of bird-window collisions at local scale, being greater in buildings surrounded by tall vegetation than in buildings surrounded by a greater proportion of urbanization (human-made structures). We call for attention on a topic that has been poorly evaluated in South America. We also encourage future scientific studies to evaluate additional risk factors and mitigation strategies accordingly, to provide a better understanding of bird-window collisions particularly in a highly biodiverse region as South America.
Alveolar bone repair of rhesus monkeys by using BMP-2 gene and mesenchymal stem cells loaded three-dimensional printed bioglass scaffold
Authors: Wang Liyan , Xu Weikang , Chen Yang , Wang Jingjing
Published: December 2019

Over the past years, the study about bone tissue engineering in the field of regenerative medicine has been a main research topic. Using three-dimensional (3D) porous degradable scaffold complexed with mesenchymal stem cells (MSCs) and growth factor gene to improve bone tissue repair and regeneration has raised much interest. This study mainly evaluated the osteogenesis of alveolar bone defects of animal in the following experimental groups: sham-operated (SO), 3D printed bioglass (3D-BG), 3D-BG with BMP-2 gene loaded CS (3D-BG + BMP/CS) and 3D-BG with rhesus marrow bone MSCs and BMP/CS (3D-BG + BMP/CS + rBMSCs). Simulated human bone defect with critical size of 10 × 10 × 5 mm were established in quadrumana - rhesus monkeys, and in vivo osteogenesis was characterized by X-ray, micro-Computed Tomography (mCT) and history. Our results revealed that 3D-BG + rBMSCs + BMP/CS scaffold could improve bone healing best by showing its promote osteogenic properties in vivo. Considering the great bone repair capacity of 3D-BG + BMP/CS + rBMSCs in humanoid primate rhesus monkeys, it could be a promising therapeutic strategy for surgery trauma or accidents, especially for alveolar bones defects.
Snowfall Variability Dictates Glacier Mass Balance Variability in Himalaya-Karakoram
Authors: Kumar Pankaj , Saharwardi Md. Saquib , Banerjee Argha , Azam Mohd. Farooq , Dubey Aditya Kumar , Murtugudde Raghu
Published: December 2019

Glaciers in the Himalaya-Karakoram (HK) are critical for ensuring water-security of a large fraction of world’s population that is vulnerable to climate impacts. However, the sensitivity of HK glaciers to changes in meteorological forcing remains largely unknown. We analyzed modelled interannual variability of mass balance (MB) that is validated against available observations, to quantify the sensitivity of MB to meteorological factors over the HK. Within the model, snowfall variability (0.06 m/yr) explains ~60% of the MB variability (0.28 m/yr), implying a sensitivity of MB on snowfall to the tune of several hundreds of percent. This stunningly high sensitivity of MB to snowfall offers crucial insights into the mechanism of the recent divergent glacier response over the HK. Our findings underscore the need for sustained measurements and model representations of the spatiotemporal variability of snowfall, one of the least-studied factors over the glacierized HK, for capturing the large-scale and yet region-specific glacier changes taking place over the HK.
Schinus terebinthifolia leaf lectin (SteLL) has anti-infective action and modulates the response of Staphylococcus aureus-infected macrophages
Authors: de Souza Feitosa Lima Isana Maria , Zagmignan Adrielle , Santos Deivid Martins , Maia Hermerson Sousa , dos Santos Silva Lucas , da Silva Cutrim Brenda , Vieira Silvamara Leite , Bezerra Filho Clovis Macêdo , de Sousa Eduardo Martins , Napoleão Thiago Henrique , Krogfelt Karen Angeliki , Løbner-Olesen Anders , Paiva Patrícia Maria Guedes , Nascimento da Silva Luís Cláudio
Published: December 2019

Staphylococcus aureus is recognized as an important pathogen causing a wide spectrum of diseases. Here we examined the antimicrobial effects of the lectin isolated from leaves of Schinus terebinthifolia Raddi (SteLL) against S. aureus using in vitro assays and an infection model based on Galleria mellonella larvae. The actions of SteLL on mice macrophages and S. aureus-infected macrophages were also evaluated. SteLL at 16 µg/mL (8 × MIC) increased cell mass and DNA content of S. aureus in relation to untreated bacteria, suggesting that SteLL impairs cell division. Unlike ciprofloxacin, SteLL did not induce the expression of recA, crucial for DNA repair through SOS response. The antimicrobial action of SteLL was partially inhibited by 50 mM N-acetylglucosamine. SteLL reduced staphyloxathin production and increased ciprofloxacin activity towards S. aureus. This lectin also improved the survival of G. mellonella larvae infected with S. aureus. Furthermore, SteLL induced the release of cytokines (IL-6, IL-10, IL-17A, and TNF-α), nitric oxide and superoxide anion by macrophagens. The lectin improved the bactericidal action of macrophages towards S. aureus; while the expression of IL-17A and IFN-γ was downregulated in infected macrophages. These evidences suggest SteLL as important lead molecule in the development of anti-infective agents against S. aureus.
The myopia susceptibility locus vasoactive intestinal peptide receptor 2 (VIPR2) contains variants with opposite effects
Authors: Leung Kim Hung , Luo Shumeng , Kwarteng Regina , Chen Sin-Guang , Yap Maurice K. H. , Huang Chien-Ling , Yip Shea Ping
Published: December 2019

Myopia is the commonest eye disorder in the world. High myopes are predisposed to ocular pathologies. The vasoactive intestinal peptide receptor 2 (VIPR2) gene was identified as a myopia susceptibility locus by our group and another group. We continued to fine-map this locus. A case-control study was performed in 4 sequential stages with a total of 941 highly myopic subjects and 846 control subjects, all unrelated Chinese. Stage 1 experimentally genotyped 64.4% of the entire cohort for 152 single-nucleotide polymorphisms (SNPs) and Stage 2 the remaining subjects for 21 SNPs. Stage 3 combined the genotypes for 21 SNPs for the entire cohort, and identified one group of high-risk haplotypes and one group of protective haplotypes significantly associated with high myopia. Stage 4 imputed genotypes for variants in theVIPR2region and identified two independent groups of variants: one group with high-risk minor alleles and another with protective minor alleles. Variants within each group were generally in strong linkage disequilibrium among themselves while high-risk variants were in linkageequilibriumwith protective variants. Therefore, theVIPR2locus seems to contain variants with opposite effects. This is the first study that has examined the genetic architecture of a myopia susceptibility locus in detail.
Mitogenomics suggests a sister relationship of Relicanthus daphneae (Cnidaria: Anthozoa: Hexacorallia: incerti ordinis) with Actiniaria
Authors: Xiao Madelyne , Brugler Mercer R. , Broe Michael B. , Gusmão Luciana C. , Daly Marymegan , Rodríguez Estefanía
Published: December 2019

Relicanthus daphneae (formerly Boloceroides daphneae) was first described in 2006 as a giant sea anemone based on morphology. In 2014, its classification was challenged based on molecular data: using five genes, Relicanthus was resolved sister to zoanthideans, but with mixed support. To better understand the evolutionary relationship of Relicanthus with other early-branching metazoans, we present 15 newly-sequenced sea anemone mitochondrial genomes and a mitogenome-based phylogeny including all major cnidarian groups, sponges, and placozoans. Our phylogenetic reconstruction reveals a moderately supported sister relationship between Relicanthus and the Actiniaria. Morphologically, the cnidae of Relicanthus has apical flaps, the only existing synapomorphy for sea anemones. Based on both molecular and morphological results, we propose a third suborder (Helenmonae) within the Actiniaria to accommodate Relicanthus. Although Relicanthus shares the same gene order and content with other available actiniarian mitogenomes, it is clearly distinct at the nucleotide level from anemones within the existing suborders. The phylogenetic position of Relicanthus could reflect its association with the periphery of isolated hydrothermal vents, which, although patchy and ephemeral, harbor unique chemosynthetic communities that provide a relatively stable food source to higher trophic levels over long evolutionary timescales. The ability to colonize the deep sea and the periphery of new vent systems may be facilitated by Relicanthus’ large and extremely yolky eggs.
Eco-friendly and biodegradable cellulose hydrogels produced from low cost okara: towards non-toxic flexible electronics
Authors: Cui Xi , Lee Jaslyn J. L. , Chen Wei Ning
Published: December 2019

With increasing resource shortage and environmental pollution, it is preferable to utilize materials which are sustainable and biodegradable. Side-streams products generated from the food processing industry is one potential avenue that can be used in a wide range of applications. In this study, the food by-product okara was effectively reused for the extraction of cellulose. Then, the okara cellulose was further employed to fabricate cellulose hydrogels with favorable mechanical properties, biodegrablability, and non-cytotoxicity. The results showed that it could be biodegraded in soil within 28 days, and showed no cytotoxicity on NIH3T3 cells. As a proof of concept, a demostration of wearable and biocompatible strain sensor was achieved, which allowed a good and stable detection of human body movement behaviors. The okara-based hydrogels could provide an alternative platform for further physical and/or chemical modification towards tissue engineering, medical supplies, or smart biomimetic soft materials.
Participation of 5-lipoxygenase and LTB4 in liver regeneration after partial hepatectomy
Authors: Lorenzetti Florencia , Vera Marina Cecilia , Ceballos María Paula , Ronco María Teresa , Pisani Gerardo Bruno , Monti Juan Alberto , Lucci Alvaro , Comanzo Carla Gabriela , Tordjmann Thierry , Carrillo María Cristina , Quiroga Ariel Darío , Alvarez María de Luján
Published: December 2019

Regeneration is the unmatched liver ability for recovering its functional mass after tissue lost. Leukotrienes (LT) are a family of eicosanoids with the capacity of signaling to promote proliferation. We analyzed the impact of blocking LT synthesis during liver regeneration after partial hepatectomy (PH). Male Wistar rats were subjected to two-third PH and treated with zileuton, a specific inhibitor of 5-lipoxygenase (5-LOX). Our first find was a significant increment of intrahepatic LTB4 during the first hour after PH together with an increase in 5-LOX expression. Zileuton reduced hepatic LTB4 levels at the moment of hepatectomy and also inhibited the increase in hepatic LTB4. This inhibition produced a delay in liver proliferation as seen by decreased PCNA and cyclin D1 nuclear expression 24 h post-PH. Results also showed that hepatic LTB4 diminution by zileuton was associated with a decrease in NF-ĸB activity. Additionally, decreased hepatic LTB4 levels by zileuton affected the recruitment of neutrophils and macrophages. Non-parenchymal cells (NPCs) from zileuton-treated PH-rats displayed higher apoptosis than NPCs from PH control rats. In conclusion, the present work provides evidences that 5-LOX activation and its product LTB4 are involved in the initial signaling events for liver regeneration after PH and the pharmacological inhibition of this enzyme can delay the initial time course of the phenomenon.
Anomalous Stranski-Krastanov growth of (111)-oriented quantum dots with tunable wetting layer thickness
Authors: Schuck Christopher F. , Roy Simon K. , Garrett Trent , Yuan Qing , Wang Ying , Cabrera Carlos I. , Grossklaus Kevin A. , Vandervelde Thomas E. , Liang Baolai , Simmonds Paul J.
Published: December 2019

Driven by tensile strain, GaAs quantum dots (QDs) self-assemble on In0.52Al0.48As(111)A surfaces lattice-matched to InP substrates. In this study, we show that the tensile-strained self-assembly process for these GaAs(111)A QDs unexpectedly deviates from the well-known Stranski-Krastanov (SK) growth mode. Traditionally, QDs formed via the SK growth mode form on top of a flat wetting layer (WL) whose thickness is fixed. The inability to tune WL thickness has inhibited researchers’ attempts to fully control QD-WL interactions in these hybrid 0D-2D quantum systems. In contrast, using microscopy, spectroscopy, and computational modeling, we demonstrate that for GaAs(111)A QDs, we can continually increase WL thickness with increasing GaAs deposition, even after the tensile-strained QDs (TSQDs) have begun to form. This anomalous SK behavior enables simultaneous tuning of both TSQD size and WL thickness. No such departure from the canonical SK growth regime has been reported previously. As such, we can now modify QD-WL interactions, with future benefits that include more precise control of TSQD band structure for infrared optoelectronics and quantum optics applications.
Deciphering the metabolic capabilities of Bifidobacteria using genome-scale metabolic models
Authors: Devika N. T. , Raman Karthik
Published: December 2019

Bifidobacteria, the initial colonisers of breastfed infant guts, are considered as the key commensals that promote a healthy gastrointestinal tract. However, little is known about the key metabolic differences between different strains of these bifidobacteria, and consequently, their suitability for their varied commercial applications. In this context, the present study applies a constraint-based modelling approach to differentiate between 36 important bifidobacterial strains, enhancing their genome-scale metabolic models obtained from the AGORA (Assembly of Gut Organisms through Reconstruction and Analysis) resource. By studying various growth and metabolic capabilities in these enhanced genome-scale models across 30 different nutrient environments, we classified the bifidobacteria into three specific groups. We also studied the ability of the different strains to produce short-chain fatty acids, finding that acetate production is niche- and strain-specific, unlike lactate. Further, we captured the role of critical enzymes from the bifid shunt pathway, which was found to be essential for a subset of bifidobacterial strains. Our findings underline the significance of analysing metabolic capabilities as a powerful approach to explore distinct properties of the gut microbiome. Overall, our study presents several insights into the nutritional lifestyles of bifidobacteria and could potentially be leveraged to design species/strain-specific probiotics or prebiotics.
Full-Length Transcriptome Survey and Expression Analysis of Parasitoid Wasp Chouioia cunea upon Exposure to 1-Dodecene
Authors: Pan Lina , Guo Meiqi , Jin Xin , Sun Zeyang , Jiang Hao , Han Jiayi , Wang Yonghui , Yan Chuncai , Li Min
Published: December 2019

Chouioia cunea (Yang) is an endoparasitic wasp which parasitizes pupae and thus plays an important role in the biological control of the fall webworm (Hyphantria cunea Drury), an important quarantine pest in the entire world and a major invasive pest in China. For the purposes of investigating which proteins are involved in the response of C. cunea to 1-Docecene, one of the chemical compounds of pupae of H. cunea with a significant attracting action to mated female C. cunea, 11.5 Gb transcriptome data was sequenced on the PacBio RS II platform from 1-day old C. cunea adults to generate a reference assembly. Afterwards, 46.88 Gb of clean RNA-Seq data were obtained to assess the transcriptional response of these insects before and after the stimulation with 1-Docecene. After removing redundancy using CD-HIT, a sequence structure analysis predicted 29,105 complete coding sequence (CDS) regions, 51,458 single-sequence repeats (SSRs), and 2,375 long non-coding RNAs. Based on the early transcriptome sequencing in our laboratory, we revealed some new sequences corresponding to chemosensory genes such as odorant binding proteins (OBPs), odorant receptor (OR), gustatory receptors(GRs). Results of quantitative real-time PCR experiments revealed that CcOBP7, CcOBP18, CcCSP4, CcOR2, and CcGR18 were up-regulated after 1-Dodecene stimulation. In addition, the expression of 31 genes, including 1 gene related to phospholipid biosynthesis and 2 genes related to transmembrane transport were up-regulated after 1-Dodecene stimulation; meanwhile, the expression of 22 genes, including 5 genes related to protein phosphorylation and protein serine/threonine kinase activity were significantly down-regulated after 1-Dodecene stimulation. These results suggest that the attraction of adult C. cunea to 1-dodecane is associated with the transmembrane signal transduction and dephosphorylation of some proteins. Our findings will provide useful targets for further studies on the molecular mechanism of host recognition in C. cunea.
A new bioluminescence-based tool for modulating target proteins in live cells
Authors: Ishimoto Tetsuya , Mori Hisashi
Published: December 2019

We have developed a new genetically encoded tool designed to generate reactive oxygen species (ROS) at target proteins in cultured cells; it is designed using firefly luciferase and photosensitiser protein KillerRed. Targeting this fusion protein, KillerFirefly, to F-actin in live cells and treatment with luciferin induced a characteristic structure, previously reported as a cofilin-actin rod, which is seen in patients with Alzheimer’s disease. This structural change is considered to be elicited by the consistent generation of very low-level ROS by KillerFirefly in the vicinity of F-actin. Moreover, our results suggest the presence of an actin-regulating system, controlled by very low levels of endogenously generated ROS.
Population genomics of two congeneric Palaearctic shorebirds reveals differential impacts of Quaternary climate oscillations across habitats types
Authors: Tan Hui Zhen , Ng Elize Ying Xin , Tang Qian , Allport Gary A. , Jansen Justin J. F. J. , Tomkovich Pavel S. , Rheindt Frank E.
Published: December 2019

Intracontinental biotic divisions across the vast Palaearctic region are not well-characterized. Past research has revealed patterns ranging from a lack of population structure to deep divergences along varied lines of separation. Here we compared biogeographic patterns of two Palaearctic shorebirds with different habitat preferences, Whimbrel (Numenius phaeopus) and Eurasian curlew (N. arquata). Using genome-wide markers from populations across the Palaearctic, we applied a multitude of population genomic and phylogenomic approaches to elucidate population structure. Most importantly, we tested for isolation by distance and visualized barriers and corridors to gene flow. We found shallow Palaearctic population structure in subpolar bog and tundra-breeding whimbrels, consistent with other species breeding at a similarly high latitude, indicating connectivity across the tundra belt, both presently and during southward shifts in periods of global cooling. In contrast, the temperate grassland-breeding Eurasian curlew emerged in three distinct clades corresponding to glacial refugia. Barriers to gene flow coincided with areas of topographic relief in the central Palaearctic for whimbrels and further east for Eurasian curlews. Our findings highlight the interplay of historic and ecological factors in influencing present-day population structure of Palaearctic biota.
Mechanism study on highly efficient polymer light-emitting diodes utilizing double-layered alkali halide electron injection layer
Authors: Niu Qiaoli , Tong Jing , Duan Xiaomeng , Zhang Haoran , Wang Dexu , Hai Gang , Lv Hao , Zeng Wenjin , Xia Ruidong , Min Yonggang
Published: December 2019

Enhancing the injection of electron is an effective strategy to improve the performance of polymer light-emitting diodes (PLEDs). In this work, we reported a 286% improvement in current efficiency (CE) of PLEDs by using double-layered alkali halide electron injection layer (EIL) NaCl/LiF instead of LiF. A significant enhancement of electron injection was observed after inserting the NaCl layer. To understand the mechanism of such improvement, the devices with KBr/LiF and CsF/LiF as EILs were also investigated. Experimental results show that metal cation migrated under the effect of built-in electric field (Vbi), which plays the main role on the improvement of electron injection in PLEDs.
Plasma chemokines are biomarkers of disease severity, higher bacterial burden and delayed sputum culture conversion in pulmonary tuberculosis
Authors: Kumar Nathella P. , Moideen Kadar , Nancy Arul , Viswanathan Vijay , Shruthi Basavaradhya S. , Sivakumar Shanmugam , Natarajan Mohan , Kornfeld Hardy , Babu Subash
Published: December 2019

Plasma cytokines are biomarkers of disease extent and mycobacterial burden in pulmonary tuberculosis (PTB). Whether chemokines can perform the same role in PTB is not known. We examined the plasma levels of chemokines in individuals with PTB, latent TB (LTB) or healthy controls (HC) and their association with disease severity and mycobacterial burdens in PTB. We also examined the chemokines in PTB individuals at the end of anti-tuberculous chemotherapy (ATT). PTB individuals exhibited significantly higher levels of CCL1, CCL3, CXCL1, CXCL2, CXCL9 and CXCL10 in comparison to LTB and/or HC individuals. PTB individuals with bilateral or cavitary disease displayed significantly elevated levels of CCL1, CCL3, CXCL1, CXCL10 and CXCL11 compared to those with unilateral or non-cavitary disease and also exhibited a significant positive relationship with bacterial burdens. In addition, PTB individuals with slower culture conversion displayed significantly elevated levels of CCL1, CCL3, CXCL1 and CXCL9 at the time of PTB diagnosis and prior to ATT. Finally, the chemokines were significantly reduced following successful ATT. Our data demonstrate that PTB is associated with elevated levels of chemokines, which are partially reversed followed chemotherapy. Our data demonstrate that chemokines are markers of disease severity, predicting increased bacterial burden and delayed culture conversion in PTB.
Uniform and bright light emission from a 3D organic light-emitting device fabricated on a bi-convex lens by a vortex-flow-assisted solution-coating method
Authors: Park Byoungchoo , Na Seo Yeong , Bae In-Gon
Published: December 2019

We herein present the results of a study on the novel fabrication process of uniform and homogeneous semiconducting polymer layers, in this case hole-injecting and fluorescent light-emitting layers that were produced by a simple solution-coating process for 3D conformal organic light-emitting diodes (3D OLEDs) on curvilinear surfaces. The solution-coating process used was a newly developed method of vortex-flow-assisted solution-coating with the support of spinning of the coating solution. It is shown that the vortex-flow-assisted spin-coating process can produce high-quality thin films at nanoscale thicknesses by controlling the liquid surface of the coating solutions, which can easily be adjusted by changing the spinning speed, even on complex curvilinear surfaces, i.e., a quasi-omnidirectional coating. This excellent film-forming ability without any serious film defects is mainly due to the reduction of line tension among the solution, air, and the substrate at the contact line due to vortex flows of the coating solution on the substrate during the vortex-spin-coating process. As a proof of concept, we present vortex-spin-coated 3D OLEDs fabricated on bi-convex lens substrates which exhibit excellent device performance with high brightness and current efficiency levels comparable to those of a conventional spin-coated 2D planar OLED on a flat substrate. It is also shown that the EL emission from the 3D OLED on the bi-convex lens substrate exhibits a diffusive Lambertian radiation pattern. The results here demonstrate that the vortex-flow-assisted spin-coating process is a promising approach for producing efficient and reliable next-generation OLEDs for 3D conformal opto-electronics.
Analysis of Dose-response Relationship between BMI and Hypertension in Northeastern China Using Restricted Cubic Spline Functions
Authors: Qu Yangming , Niu HuiKun , Li Lu , Li Meiqi , Yan Shoumeng , Li Meng , Jiang Shan , Ma Xiaoyu , Li Bo , Wu Hui
Published: December 2019

High body mass index (BMI) was significantly associated with hypertension. The purpose of this study is to investigate the association between BMI and hypertension in people in northeast China. Our study was a cross-sectional study conducted from June to August 2012. According to multistage, stratified cluster sampling, a total of 21435 inhabitants aged between 18 and 79 years in Jilin Province were selected randomly. The prevalence of hypertension was 35.66% overall. After adjusting for potential confounders, the multivariable-adjusted odds ratios for the BMI- hypertension association for overweight and obesity were 2.503 (95% confidence interval = 1.912–2.204) and 4.259 (95% confidence interval = 3.883–4.671). The results of multivariable restricted cubic spline regression analysis showed that there was a non-linear relationship between the continuous change of BMI and hypertension (P < 0.001) after adjusting the confounding factors of different genders and age groups, which indicated that there was an adjusted dose-response association between continuous BMI and hypertension.