bluuebunny/crossref_metadata_2025_split huggingface dataset:
A polygenic resilience score moderates the genetic risk for schizophrenia
Authors:   the Schizophrenia Working Group of the Psychiatric Genomics Consortium, Hess Jonathan L. ,   Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Tylee Daniel S. , Mattheisen Manuel , Børglum Anders D. , Als Thomas D. , Grove Jakob , Werge Thomas , Mortensen Preben Bo , Mors Ole , Nordentoft Merete , Hougaard David M. , Byberg-Grauholm Jonas , Bækvad-Hansen Marie , Greenwood Tiffany A. , Tsuang Ming T. , Curtis David , Steinberg Stacy , Sigurdsson Engilbert , Stefánsson Hreinn , Stefánsson Kári , Edenberg Howard J. , Holmans Peter , Faraone Stephen V. , Glatt Stephen J. 
Published: September 2019

AbstractBased on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known “polygenic resilience score” that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.
Diversity and biogeography of SAR11 bacteria from the Arctic Ocean
Authors: Kraemer Susanne , Ramachandran Arthi , Colatriano David , Lovejoy Connie , Walsh David A 
Published: September 2019

Abstract
The Arctic Ocean is relatively isolated from other oceans and consists of strongly stratified water masses with distinct histories, nutrient, temperature, and salinity characteristics, therefore providing an optimal environment to investigate local adaptation. The globally distributed SAR11 bacterial group consists of multiple ecotypes that are associated with particular marine environments, yet relatively little is known about Arctic SAR11 diversity. Here, we examined SAR11 diversity using ITS analysis and metagenome-assembled genomes (MAGs). Arctic SAR11 assemblages were comprised of the S1a, S1b, S2, and S3 clades, and structured by water mass and depth. The fresher surface layer was dominated by an ecotype (S3-derived P3.2) previously associated with Arctic and brackish water. In contrast, deeper waters of Pacific origin were dominated by the P2.3 ecotype of the S2 clade, within which we identified a novel subdivision (P2.3s1) that was rare outside the Arctic Ocean. Arctic S2-derived SAR11 MAGs were restricted to high latitudes and included MAGs related to the recently defined S2b subclade, a finding consistent with bi-polar ecotypes and Arctic endemism. These results place the stratified Arctic Ocean into the SAR11 global biogeography and have identified SAR11 lineages for future investigation of adaptive evolution in the Arctic Ocean.
Drug repurposing for Alzheimer’s disease based on transcriptional profiling of human iPSC-derived cortical neurons
Authors: Williams Gareth , Gatt Ariana , Clarke Earl , Corcoran Jonathan , Doherty Patrick , Chambers David , Ballard Clive 
Published: September 2019

AbstractAlzheimer’s disease is a complex disorder encompassing multiple pathological features with associated genetic and molecular culprits. However, target-based therapeutic strategies have so far proved ineffective. The aim of this study is to develop a methodology harnessing the transcriptional changes associated with Alzheimer’s disease to develop a high content quantitative disease phenotype that can be used to repurpose existing drugs. Firstly, the Alzheimer’s disease gene expression landscape covering severe disease stage, early pathology progression, cognitive decline and animal models of the disease has been defined and used to select a set of 153 drugs tending to oppose disease-associated changes in the context of immortalised human cancer cell lines. The selected compounds have then been assayed in the more biologically relevant setting of iPSC-derived cortical neuron cultures. It is shown that 51 of the drugs drive expression changes consistently opposite to those seen in Alzheimer’s disease. It is hoped that the iPSC profiles will serve as a useful resource for drug repositioning within the context of neurodegenerative disease and potentially aid in generating novel multi-targeted therapeutic strategies.
Megakaryocytes participate in the occurrence of bleomycin-induced pulmonary fibrosis
Authors: Zhou Yan , Zhang Bo , Li Chen , Huang XiaoTing , Cheng HaiPeng , Bao XingWen , Zhao FeiYan , Cheng QingMei , Yue ShaoJie , Han JianZhong , Luo ZiQiang 
Published: September 2019

AbstractPulmonary fibrosis is characterized by the remodeling of fibrotic tissue and collagen deposition, which mainly results from aberrant fibroblasts proliferation and trans-differentiation to myofibroblasts. Patients with chronic myelogenous leukemia, myeloproliferative disorder, and scleroderma with pulmonary fibrosis complications show megakaryocyte infiltration in the lung. In this study, we demonstrated that the number of CD41+ megakaryocytes increased in bleomycin (BLM)-induced lung fibrosis tissues through the Chemokine (CXCmotif) ligand 12/Chemokine receptor 4 (CXCL12/CXCR4) axis. Pharmacological inhibition of the CXCL12/CXCR4 axis with WZ811 prevented migration of CD41+ megakaryocytes induced by BLM-injured lung tissue ex vivo and in vivo. In addition, WZ811 significantly attenuated lung fibrosis after BLM challenge. Moreover, megakaryocytes directly promoted fibroblast proliferation and trans-differentiation to myofibroblasts. We conclude that thrombopoietin (TPO) activated megakaryocytes through transforming growth factor β (TGF-β) pathway to promote fibroblast proliferation and trans-differentiation to myofibroblasts, which is abolished by treatment with selective TGF-βR-1/ALK5 inhibitors. Therefore, CD41+ megakaryocytes migrate to injured lung tissue partially through the CXCL12/CXCR4 axis to promote the proliferation and trans-differentiation of fibroblasts through direct contact and the TGF-β1 pathway.
Large-scale parallelization of nanomechanical mass spectrometry with weakly-coupled resonators
Authors: Stassi Stefano , De Laurentis Giulia , Chakraborty Debadi , Bejtka Katarzyna , Chiodoni Angelica , Sader John E. , Ricciardi Carlo 
Published: September 2019

AbstractNanomechanical mass spectrometry is a recent technological breakthrough that enables the real-time analysis of single molecules. In contraposition to its extreme mass sensitivity is a limited capture cross-section that can hinder measurements in a practical setting. Here we show that weak-coupling between devices in resonator arrays can be used in nanomechanical mass spectrometry to parallelize the measurement. This coupling gives rise to asymmetric amplitude peaks in the vibrational response of a single nanomechanical resonator of the array, which coincide with the natural frequencies of all other resonators in the same array. A rigorous theoretical model is derived that explains the physical mechanisms and describes the practical features of this parallelization. We demonstrate the significance of this parallelization through inertial imaging of analytes adsorbed to all resonators of an array, with the possibility of simultaneously detecting resonators placed at distances a hundred times larger than their own physical size.
Space Station conditions are selective but do not alter microbial characteristics relevant to human health
Authors: Mora Maximilian , Wink Lisa , Kögler Ines , Mahnert Alexander , Rettberg Petra , Schwendner Petra , Demets René , Cockell Charles , Alekhova Tatiana , Klingl Andreas , Krause Robert , Zolotariof Anna , Alexandrova Alina , Moissl-Eichinger Christine 
Published: September 2019

AbstractThe International Space Station (ISS) is a unique habitat for humans and microorganisms. Here, we report the results of the ISS experiment EXTREMOPHILES, including the analysis of microbial communities from several areas aboard at three time points. We assess microbial diversity, distribution, functional capacity and resistance profile using a combination of cultivation-independent analyses (amplicon and shot-gun sequencing) and cultivation-dependent analyses (physiological and genetic characterization of microbial isolates, antibiotic resistance tests, co-incubation experiments). We show that the ISS microbial communities are highly similar to those present in ground-based confined indoor environments and are subject to fluctuations, although a core microbiome persists over time and locations. The genomic and physiological features selected by ISS conditions do not appear to be directly relevant to human health, although adaptations towards biofilm formation and surface interactions were observed. Our results do not raise direct reason for concern with respect to crew health, but indicate a potential threat towards material integrity in moist areas.
Evidence for allocentric boundary and goal direction information in the human entorhinal cortex and subiculum
Authors: Shine J. P. , Valdés-Herrera J. P. , Tempelmann C. , Wolbers T. 
Published: September 2019

AbstractIn rodents, cells in the medial entorhinal cortex (EC) and subiculum code for the allocentric direction to environment boundaries, which is an important prerequisite for accurate positional coding. Although in humans boundary-related signals have been reported, there is no evidence that they contain allocentric direction information. Furthermore, it has not been possible to separate boundary versus goal direction signals in the EC/subiculum. Here, to address these questions, we had participants learn a virtual environment containing four unique boundaries. Participants then underwent fMRI scanning where they made judgements about the allocentric direction of a cue object. Using multivariate decoding, we found information regarding allocentric boundary direction in posterior EC and subiculum, whereas allocentric goal direction was decodable from anterior EC and subiculum. These data provide the first evidence of allocentric boundary coding in humans, and are consistent with recent conceptualisations of a division of labour within the EC.
Highly efficient decomposition of ammonia using high-entropy alloy catalysts
Authors: Xie Pengfei , Yao Yonggang , Huang Zhennan , Liu Zhenyu , Zhang Junlei , Li Tangyuan , Wang Guofeng , Shahbazian-Yassar Reza , Hu Liangbing , Wang Chao 
Published: September 2019

AbstractAmmonia represents a promising liquid fuel for hydrogen storage, but its large-scale application is limited by the need for precious metal ruthenium (Ru) as catalyst. Here we report on highly efficient ammonia decomposition using novel high-entropy alloy (HEA) catalysts made of earth abundant elements. Quinary CoMoFeNiCu nanoparticles are synthesized in a single solid-solution phase with robust control over the Co/Mo atomic ratio, including those ratios considered to be immiscible according to the Co-Mo bimetallic phase diagram. These HEA nanoparticles demonstrate substantially enhanced catalytic activity and stability for ammonia decomposition, with improvement factors achieving >20 versus Ru catalysts. Catalytic activity of HEA nanoparticles is robustly tunable by varying the Co/Mo ratio, allowing for the optimization of surface property to maximize the reactivity under different reaction conditions. Our work highlights the great potential of HEAs for catalyzing chemical transformation and energy conversion reactions.
Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening
Authors: Kim Minsuh , Mun Hyemin , Sung Chang Oak , Cho Eun Jeong , Jeon Hye-Joon , Chun Sung-Min , Jung Da Jung , Shin Tae Hoon , Jeong Gi Seok , Kim Dong Kwan , Choi Eun Kyung , Jeong Seong-Yun , Taylor Alison M. , Jain Sejal , Meyerson Matthew , Jang Se Jin 
Published: September 2019

AbstractLung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung cancer organoids and normal bronchial organoids established from patient tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2-mutant organoid to olaparib, an EGFR-mutant organoid to erlotinib, and an EGFR-mutant/MET-amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.
Active control of viscous fingering using electric fields
Authors: Gao Tao , Mirzadeh Mohammad , Bai Peng , Conforti Kameron M. , Bazant Martin Z. 
Published: September 2019

AbstractViscous fingering is a widely observed phenomenon, in which finger-like instabilities occur at the interface of two fluids, whenever a less viscous phase displaces a more viscous phase. This instability is notoriously difficult to control, especially for given viscosity ratio and geometry. Here we demonstrate experimentally the active control of viscous fingering of two given liquids, for given geometry and flow rate in a Hele-Shaw cell. The control is realized by taking advantage of electro-osmotic flows along the surfaces confining the fluid, via applying an external electric field. Depending on the direction of electric field, the induced secondary electro-osmotic flows either assist or oppose the hydraulic flow, effectively reducing or increasing the flow resistance, leading to the control of interface stability. The mechanism of apparent “electrokinetic thinning/thickening” is proposed to explain the experimental observations. Theoretical predictions of linear stability are confirmed experimentally for a broad range of immiscible electrolyte displacements.
In vivo evaluation of safety, biodistribution and pharmacokinetics of laser-synthesized gold nanoparticles
Authors: Bailly Anne-Laure , Correard Florian , Popov Anton , Tselikov Gleb , Chaspoul Florence , Appay Romain , Al-Kattan Ahmed , Kabashin Andrei V. , Braguer Diane , Esteve Marie-Anne 
Published: September 2019

AbstractCapable of generating plasmonic and other effects, gold nanostructures can offer a variety of diagnostic and therapy functionalities for biomedical applications, but conventional chemically-synthesized Au nanomaterials cannot always match stringent requirements for toxicity levels and surface conditioning. Laser-synthesized Au nanoparticles (AuNP) present a viable alternative to chemical counterparts and can offer exceptional purity (no trace of contaminants) and unusual surface chemistry making possible direct conjugation with biocompatible polymers (dextran, polyethylene glycol). This work presents the first pharmacokinetics, biodistribution and safety study of laser-ablated dextran-coated AuNP (AuNPd) under intravenous administration in small animal model. Our data show that AuNPd are rapidly eliminated from the blood circulation and accumulated preferentially in liver and spleen, without inducing liver or kidney toxicity, as confirmed by the plasmatic ALAT and ASAT activities, and creatininemia values. Despite certain residual accumulation in tissues, we did not detect any sign of histological damage or inflammation in tissues, while IL-6 level confirmed the absence of any chronic inflammation. The safety of AuNPd was confirmed by healthy behavior of animals and the absence of acute and chronic toxicities in liver, spleen and kidneys. Our results demonstrate that laser-synthesized AuNP are safe for biological systems, which promises their successful biomedical applications.
Corticosteroid eye drop instillation aggravates the development of Acanthamoeba keratitis in rabbit corneas inoculated with Acanthamoeba and bacteria
Authors: Nakagawa Hayate , Koike Naohito , Ehara Tomoko , Hattori Takaaki , Narimatsu Akitomo , Kumakura Shigeto , Goto Hiroshi 
Published: September 2019

AbstractThe role of topical corticosteroids in management of Acanthamoeba keratitis (AK) remains controversial. Using a rabbit AK model, we investigated whether corticosteroid use is a risk factor of AK. Acanthamoeba (1 × 105/ml) was incubated with two densities of P. aeruginosa (PA; high-PA: 1 × 108/ml, low-PA: 3 × 105/ml) before corneal inoculation. Rabbit corneas were inoculated with Acanthamoeba alone or Acanthamoeba plus PA and administered levofloxacin and betamethasone sodium phosphate (BSP) eye drops for 5 or 7 days. Infected rabbit eyes were evaluated for clinical score and Acanthamoeba by histological examination. Acanthamoeba alone and BSP treatment did not produce keratitis. Corneas inoculated with Acanthamoeba plus low-PA treated immediately with levofloxacin and BSP remained clear with few infiltrates. Corneas inoculated with Acanthamoeba plus low-PA treated with levofloxacin immediately and BSP 12 h later developed severe keratitis. Corneas inoculated with Acanthamoeba plus high-PA treated immediately with levofloxacin and BSP also developed severe keratitis. Acanthamoebae were detected by PAS staining in corneas inoculated with Acanthamoeba plus high-PA treated with levofloxacin and BSP. Topical corticosteroids have the potential to aggravate AK when cornea is infected by Acanthamoeba with a critical number of bacteria or when corticosteroids are given after infection has established by Acanthamoeba with small number of bacteria.
Application of Quantum Annealing to Nurse Scheduling Problem
Authors: Ikeda Kazuki , Nakamura Yuma , Humble Travis S. 
Published: September 2019

AbstractQuantum annealing is a promising heuristic method to solve combinatorial optimization problems, and efforts to quantify performance on real-world problems provide insights into how this approach may be best used in practice. We investigate the empirical performance of quantum annealing to solve the Nurse Scheduling Problem (NSP) with hard constraints using the D-Wave 2000Q quantum annealing device. NSP seeks the optimal assignment for a set of nurses to shifts under an accompanying set of constraints on schedule and personnel. After reducing NSP to a novel Ising-type Hamiltonian, we evaluate the solution quality obtained from the D-Wave 2000Q against the constraint requirements as well as the diversity of solutions. For the test problems explored here, our results indicate that quantum annealing recovers satisfying solutions for NSP and suggests the heuristic method is potentially achievable for practical use. Moreover, we observe that solution quality can be greatly improved through the use of reverse annealing, in which it is possible to refine returned results by using the annealing process a second time. We compare the performance of NSP using both forward and reverse annealing methods and describe how this approach might be used in practice.
Varying crosslinking motifs drive the mesoscale mechanics of actin-microtubule composites
Authors: Ricketts Shea N. , Francis Madison L. , Farhadi Leila , Rust Michael J. , Das Moumita , Ross Jennifer L. , Robertson-Anderson Rae M. 
Published: September 2019

AbstractThe cytoskeleton precisely tunes its mechanics by altering interactions between semiflexible actin filaments, rigid microtubules, and crosslinking proteins. We use optical tweezers microrheology and confocal microscopy to characterize how varying crosslinking motifs impact the mesoscale mechanics and mobility of actin-microtubule composites. We show that, upon subtle changes in crosslinking patterns, composites can exhibit two distinct classes of force response – primarily elastic versus more viscous. For example, a composite in which actin and microtubules are crosslinked to each other but not to themselves is markedly more elastic than one in which both filaments are independently crosslinked. Notably, this distinction only emerges at mesoscopic scales in response to nonlinear forcing, whereas varying crosslinking motifs have little impact on the microscale mechanics and mobility. Our unexpected scale-dependent results not only inform the physics underlying key cytoskeleton processes and structures, but, more generally, provide valuable perspective to materials engineering endeavors focused on polymer composites.
Synergistic effects of tung oil and heat treatment on physicochemical properties of bamboo materials
Authors: Tang Tong , Zhang Bo , Liu Xianmiao , Wang Wenbo , Chen Xiufang , Fei Benhua 
Published: September 2019

AbstractThe search for green and sustainable modification method to produce durable bamboo materials remains a challenge in industry. Here, heat treatment in tung oil at 100–200 °C was employed to modify bamboo materials. Oil permeation and distribution in the structure of bamboo samples during heat treatment were explored. The synergistic effects of tung oil and heat treatment on the chemical, physical and mechanical properties of bamboo materials, and their mutual relationships were also investigated in detail. Results showed that the tung oil heat treated bamboo not only had an enhanced hydrophobic property and dimensional stability, improved fungi resistance, but also displayed good mechanical performance. Compared with the untreated sample, the water-saturated swelling reduced from 3.17% to 2.42% for the sample after oil heat treatment at 200 °C, and the contact angles of the sample after oil heat treatment at 200 °C can keep >100° after 300 s in radial direction. Such improvement can be attributed to changes of chemical components, increased crystallinity structure, and the formation of oily films inside or over the bamboo surface. Therefore, tung oil heat treatment can be a highly promising technology for bamboo modification in the industry.
Yeast PAF1 complex counters the pol III accumulation and replication stress on the tRNA genes
Authors: Bhalla Pratibha , Shukla Ashutosh , Vernekar Dipti Vinayak , Arimbasseri Aneeshkumar Gopalakrishnan , Sandhu Kuljeet Singh , Bhargava Purnima 
Published: September 2019

AbstractThe RNA polymerase (pol) III transcribes mostly short, house-keeping genes, which produce stable, non-coding RNAs. The tRNAs genes, highly transcribed by pol III in vivo are known replication fork barriers. One of the transcription factors, the PAF1C (RNA polymerase II associated factor 1 complex) is reported to associate with pol I and pol II and influence their transcription. We found low level PAF1C occupancy on the yeast pol III-transcribed genes, which is not correlated with nucleosome positions, pol III occupancy and transcription. PAF1C interacts with the pol III transcription complex and causes pol III loss from the genes under replication stress. Genotoxin exposure causes pol III but not Paf1 loss from the genes. In comparison, Paf1 deletion leads to increased occupancy of pol III, γ-H2A and DNA pol2 in gene-specific manner. Paf1 restricts the accumulation of pol III by influencing the pol III pause on the genes, which reduces the pol III barrier to the replication fork progression.