bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility
Authors: Washburn Halley R. , Xia Nan L. , Zhou Wei , Mao Yu-Ting , Dalva Matthew B.
Published: January 2020

Localization of the N-methyl-D-aspartate type glutamate receptor (NMDAR) to dendritic spines is essential for excitatory synaptic transmission and plasticity. Rather than remaining trapped at synaptic sites, NMDA receptors undergo constant cycling into and out of the postsynaptic density. Receptor movement is constrained by protein-protein interactions with both the intracellular and extracellular domains of the NMDAR. The role of extracellular interactions on the mobility of the NMDAR is poorly understood. Here we demonstrate that the positive surface charge of the hinge region of the N-terminal domain in the GluN1 subunit of the NMDAR is required to maintain NMDARs at dendritic spine synapses and mediates the direct extracellular interaction with a negatively charged phospho-tyrosine on the receptor tyrosine kinase EphB2. Loss of the EphB-NMDAR interaction by either mutating GluN1 or knocking down endogenous EphB2 increases NMDAR mobility. These findings begin to define a mechanism for extracellular interactions mediated by charged domains.
Publisher Correction: MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors
Authors: Chen Xinyue , Burkhardt Daniel B. , Hartman Amaleah A. , Hu Xiao , Eastman Anna E. , Sun Chao , Wang Xujun , Zhong Mei , Krishnaswamy Smita , Guo Shangqin
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: CDK2-mediated site-specific phosphorylation of EZH2 drives and maintains triple-negative breast cancer
Authors: Nie Lei , Wei Yongkun , Zhang Fei , Hsu Yi-Hsin , Chan Li-Chuan , Xia Weiya , Ke Baozhen , Zhu Cihui , Deng Rong , Tang Jun , Yao Jun , Chu Yu-Yi , Zhao Xixi , Han Ye , Hou Junwei , Huo Longfei , Ko How-Wen , Lin Wan-Chi , Yamaguchi Hirohito , Hsu Jung-Mao , Yang Yi , Pan Dean N. , Hsu Jennifer L. , Kleer Celina G. , Davidson Nancy E. , Hortobagyi Gabriel N. , Hung Mien-Chie
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis
Authors: Martinez Calejman C. , Trefely S. , Entwisle S. W. , Luciano A. , Jung S. M. , Hsiao W. , Torres A. , Hung C. M. , Li H. , Snyder N. W. , Villén J. , Wellen K. E. , Guertin D. A.
Published: January 2020

mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.
Author Correction: Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis
Authors: Dorival Jonathan , Risser Fanny , Jacob Christophe , Collin Sabrina , Dräger Gerald , Paris Cédric , Chagot Benjamin , Kirschning Andreas , Gruez Arnaud , Weissman Kira J.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Ocean circulation causes the largest freshening event for 120 years in eastern subpolar North Atlantic
Authors: Holliday N. Penny , Bersch Manfred , Berx Barbara , Chafik Léon , Cunningham Stuart , Florindo-López Cristian , Hátún Hjálmar , Johns William , Josey Simon A. , Larsen Karin Margretha H. , Mulet Sandrine , Oltmanns Marilena , Reverdin Gilles , Rossby Tom , Thierry Virginie , Valdimarsson Hedinn , Yashayaev Igor
Published: January 2020

The Atlantic Ocean overturning circulation is important to the climate system because it carries heat and carbon northward, and from the surface to the deep ocean. The high salinity of the subpolar North Atlantic is a prerequisite for overturning circulation, and strong freshening could herald a slowdown. We show that the eastern subpolar North Atlantic underwent extreme freshening during 2012 to 2016, with a magnitude never seen before in 120 years of measurements. The cause was unusual winter wind patterns driving major changes in ocean circulation, including slowing of the North Atlantic Current and diversion of Arctic freshwater from the western boundary into the eastern basins. We find that wind-driven routing of Arctic-origin freshwater intimately links conditions on the North West Atlantic shelf and slope region with the eastern subpolar basins. This reveals the importance of atmospheric forcing of intra-basin circulation in determining the salinity of the subpolar North Atlantic.
Urban areas as hotspots for bees and pollination but not a panacea for all insects
Authors: Theodorou Panagiotis , Radzevičiūtė Rita , Lentendu Guillaume , Kahnt Belinda , Husemann Martin , Bleidorn Christoph , Settele Josef , Schweiger Oliver , Grosse Ivo , Wubet Tesfaye , Murray Tomás E. , Paxton Robert J.
Published: January 2020

Urbanisation is an important global driver of biodiversity change, negatively impacting some species groups whilst providing opportunities for others. Yet its impact on ecosystem services is poorly investigated. Here, using a replicated experimental design, we test how Central European cities impact flying insects and the ecosystem service of pollination. City sites have lower insect species richness, particularly of Diptera and Lepidoptera, than neighbouring rural sites. In contrast, Hymenoptera, especially bees, show higher species richness and flower visitation rates in cities, where our experimentally derived measure of pollination is correspondingly higher. As well as revealing facets of biodiversity (e.g. phylogenetic diversity) that correlate well with pollination, we also find that ecotones in insect-friendly green cover surrounding both urban and rural sites boost pollination. Appropriately managed cities could enhance the conservation of Hymenoptera and thereby act as hotspots for pollination services that bees provide to wild flowers and crops grown in urban settings.
Author Correction: Realization of Lieb lattice in covalent-organic frameworks with tunable topology and magnetism
Authors: Cui Bin , Zheng Xingwen , Wang Jianfeng , Liu Desheng , Xie Shijie , Huang Bing
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Annular flexible thermoelectric devices with integrated-module architecture
Authors: Qu Dawei , Huang Xuan , Li Xin , Wang Hanfu , Chen Guangming
Published: January 2020

Organic and composite thermoelectric (TE) materials have witnessed explosive developments in recent years. Design strategy of their flexible devices is vital to achieve high performance and suit various application environments. Here, we propose a design strategy of annular flexible TE devices with integrated-module architecture, where the independent modules made up of alternatively connected p-n couples are connected in series, and then rounded head-to-tail into annular configuration. The achieved devices can not only save plenty of space owing to their highly integrated structure design, but also be directly mounted on cylindrical objects (like pipes) to suit versatile applications. More importantly, the annular TE devices display excellent performances, superior to most previous work and the traditional serial single-layer film structure. For example, the annular device with eight modules consisting of three p-n couples reveals an output power of 12.37 μW at a temperature gradient of 18 K, much higher than that of the corresponding single-layer film structure (1.74 μW). The integration process is simple and easy to scale up. This architecture design strategy will greatly speed up the TE applications and benefit the research of organic and composite TE materials.
Author Correction: Genomic and phenotypic analyses of six offspring of a genome-edited hornless bull
Authors: Young Amy E. , Mansour Tamer A. , McNabb Bret R. , Owen Joseph R. , Trott Josephine F. , Brown C. Titus , Van Eenennaam Alison L.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A Hyaluronan-binding Peptide (P15-1) Reduces Inflammatory and Catabolic Events in IL-1β-treated Human Articular Chondrocytes
Authors: Shortt Claire , Luyt Leonard G. , Turley Eva A. , Cowman Mary K. , Kirsch Thorsten
Published: January 2020

Inflammation plays a critical role in osteoarthritis (OA). It stimulates catabolic events in articular chondrocytes and prevents chondrogenic precursor cells from repairing cartilage lesions, leading to accelerated cartilage degradation. Therefore, the identification of novel factors that reduce catabolic events in chondrocytes and enhances chondrogenic differentiation of precursor cells in an inflammatory environment may provide novel therapeutic strategies for the treatment of OA. The goal of this study was to determine whether a hyaluronan (HA)-binding peptide (P15-1), via interacting with high molecular weight (HMW)HA can enhance the anti-inflammatory properties of HMWHA and decrease catabolic events in interleukin-1beta (IL-1β)-treated human articular chondrocytes. Treatment with P15-1 decreased catabolic events and stimulated anabolic events in articular chondrocytes cultured in an inflammatory environment. P15-1 pre-mixed with HMWHA was more effective in inhibiting catabolic events and stimulating anabolic events than P15-1 or HMWHA alone. Our findings suggest that P15-1 together with HMWHA inhibits catabolic events in articular chondrocytes via the inhibition of p38 mitogen-activated protein kinases (MAPK) and increasing the thickness of the pericellular matrix (PCM) around chondrocytes thereby decreasing catabolic signaling. Finally, conditioned medium from IL-1β and P15-1-treated human articular chondrocytes was less inhibitory for chondrogenic differentiation of precursor cells than conditioned medium from chondrocytes treated with IL-1β alone. In conclusion, P15-1 is proposed to function synergistically with HMWHA to enhance the protective microenvironment for chondrocytes and mesenchymal stem cells during inflammation and regeneration.
Associations of lymphotoxin-a (LTA) rs909253 A/G gene polymorphism, plasma level and risk of ankylosing spondylitis in a Chinese Han population
Authors: Zhu Aiping , Yang Zhicheng , Zhang Hui , Liu Ruiping
Published: January 2020

Lymphotoxin-a (LTA) may be associated with the pathogenesis of inflammatory diseases. To assess the association of the LTA rs909253 A/G polymorphism with plasma level and risk of ankylosing spondylitis (AS) in a Chinese Han population. Genotyping and LTA plasma were tested by mass spectroscopy and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that the average plasma level of LTA in AS was significantly lower than in the controls (P = 0.000). Our results also indicated that LTA rs909253 A/G was associated with a decreased risk of AS (G vs. A: P = 0.014). Significant differences were also found between the rs909253 A/G genotype and down-regulated plasma level in AS patients, compared with controls. After stratification analysis, a decreased risk of AS was associated with the LTA rs909253 G allele (G vs. A) among female patients, younger patients (Yr. < 30), HLA-B27-positive patients. In addition, In conclusion, LTA rs909253 A/G genotype has a significant relationship with decreased susceptibility to AS.
Long-term metabolic consequences of acute dioxin exposure differ between male and female mice
Authors: Hoyeck Myriam P. , Blair Hannah , Ibrahim Muna , Solanki Shivani , Elsawy Mariam , Prakash Arina , Rick Kayleigh R. C. , Matteo Geronimo , O’Dwyer Shannon , Bruin Jennifer E.
Published: January 2020

Epidemiological studies have consistently shown an association between exposure to environmental pollutants and diabetes risk in humans. We have previously shown that direct exposure of mouse and human islets (endocrine pancreas) to the highly persistent pollutant TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) causes reduced insulin secretion ex vivo. Furthermore, a single high-dose of TCDD (200 µg/kg) suppressed both fasting and glucose-induced plasma insulin levels and promoted beta-cell apoptosis after 7 days in male mice. The current study investigated the longer-term effects of a single high-dose TCDD injection (20 µg/kg) on glucose metabolism and beta cell function in male and female C57Bl/6 mice. TCDD-exposed males displayed modest fasting hypoglycemia for ~4 weeks post-injection, reduced fasting insulin levels for up to 6 weeks, increased insulin sensitivity, decreased beta cell area, and increased delta cell area. TCDD-exposed females also had long-term suppressed basal plasma insulin levels, and abnormal insulin secretion for up to 6 weeks. Unlike males, TCDD did not impact insulin sensitivity or islet composition in females, but did cause transient glucose intolerance 4 weeks post-exposure. Our results show that a single exposure to dioxin can suppress basal insulin levels long-term in both sexes, but effects on glucose homeostasis are sex-dependent.
A Statistical Approach of Background Removal and Spectrum Identification for SERS Data
Authors: Wang Chuanqi , Xiao Lifu , Dai Chen , Nguyen Anh H. , Littlepage Laurie E. , Schultz Zachary D. , Li Jun
Published: January 2020

SERS (surface-enhanced Raman scattering) enhances the Raman signals, but the plasmonic effects are sensitive to the chemical environment and the coupling between nanoparticles, resulting in large and variable backgrounds, which make signal matching and analyte identification highly challenging. Removing background is essential, but existing methods either cannot fit the strong fluctuation of the SERS spectrum or do not consider the spectra’s shape change across time. Here we present a new statistical approach named SABARSI that overcomes these difficulties by combining information from multiple spectra. Further, after efficiently removing the background, we have developed the first automatic method, as a part of SABARSI, for detecting signals of molecules and matching signals corresponding to identical molecules. The superior efficiency and reproducibility of SABARSI are shown on two types of experimental datasets.
Neural Representation of Observed, Imagined, and Attempted Grasping Force in Motor Cortex of Individuals with Chronic Tetraplegia
Authors: Rastogi Anisha , Vargas-Irwin Carlos E. , Willett Francis R. , Abreu Jessica , Crowder Douglas C. , Murphy Brian A. , Memberg William D. , Miller Jonathan P. , Sweet Jennifer A. , Walter Benjamin L. , Cash Sydney S. , Rezaii Paymon G. , Franco Brian , Saab Jad , Stavisky Sergey D. , Shenoy Krishna V. , Henderson Jaimie M. , Hochberg Leigh R. , Kirsch Robert F. , Ajiboye A. Bolu
Published: January 2020

Hybrid kinetic and kinematic intracortical brain-computer interfaces (iBCIs) have the potential to restore functional grasping and object interaction capabilities in individuals with tetraplegia. This requires an understanding of how kinetic information is represented in neural activity, and how this representation is affected by non-motor parameters such asvolitional state(VoS), namely, whether one observes, imagines, or attempts an action. To this end, this work investigates how motor cortical neural activity changes when three human participants with tetraplegiaobserve, imagine, andattemptto produce three discrete hand grasping forces with the dominant hand. We show that force representation follows the same VoS-related trends as previously shown for directional arm movements; namely, that attempted force production recruits more neural activity compared to observed or imagined force production. Additionally, VoS-modulated neural activity to a greater extent than grasping force. Neural representation of forces was lower than expected, possibly due to compromised somatosensory pathways in individuals with tetraplegia, which have been shown to influence motor cortical activity. Nevertheless, attempted forces (but not always observed or imagined forces) could be decoded significantly above chance, thereby potentially providing relevant information towards the development of a hybrid kinetic and kinematic iBCI.
Assessing fuel properties effects of 2,5-dimethylfuran on microscopic and macroscopic characteristics of oxygenated fuel/diesel blends spray
Authors: Zhang Peng , Su Xin , Chen Hao , Geng Limin , Zhao Xuan
Published: January 2020

2,5-Dimethylfuran (DMF) is a type of attractive sustainable green energy for diesel engines that is designed to reduce soot emission. This study investigated the effect of fuel properties on the macroscopic and microscopic spray characteristics of four test blends under injection pressures of 90, 120 and 150 MPa and ambient pressure of 5 MPa in a common diesel rail injection system. The macroscopic results indicate that with higher density, lower viscosity and lower latent heating of DMF20, the spray tip penetration and spray area are increased and the average spray angle is slightly increased. Interestingly, the effect of latent heating on the average spray angle is more obvious than that of kinematic viscosity. The microscopic results suggest that higher density, lower viscosity and lower latent heating of DMF20 have an adverse effect on the breakup of small droplets. The results of comparative analysis show that the change rules of the spray parameters remain nearly unchanged with increased injection pressure, and the influence of DMF20 properties produces a different change in different spray parameters with increasing injection pressure. The meaningful conclusion is that the properties of DMF are favourable to improvement of the spray and atomization parameters under high injection pressure.
Influence of the magnetic field on bandgap and chemical composition of zinc thin films prepared by sparking discharge process
Authors: Ručman Stefan , Intra Panich , Kantarak E. , Sroila W. , Kumpika T. , Jakmunee J. , Punyodom W. , Arsić Biljana , Singjai Pisith
Published: January 2020

We examine the influence of the magnetic field on the chemical reaction of nitrogen and carbon dioxide in sparking electric discharge of zinc wires. Samples are prepared on Indium Tin Oxide (ITO) and quartz substrates in the form of thin films at 0 T, 0.2 T and 0.4 T. Different chemical composition of thin-films prepared by sparking discharge was obtained and verified by XPS, Raman and Cyclic voltammetry. Carbon dioxide conversion to carbonates was observed for zinc sparked in CO2 and nitrogen affecting crystallization of thin films was confirmed by XRD. Synthesis route for thin-film preparation used in this study is electric sparking discharge, convenient for fast ionization of metal and gasses. Band gap energy of thin films prepared by this method was starting from 2.81 eV and 4.24 eV, with the lowest band gaps prepared on ITO in 0.4 T. Differential Mobility Analysis (DMA) indicates smaller particles are fabricated by discharging zinc wires in a higher magnetic field. Nitridification of zinc nanoparticles occurred on 0.2 Tesla magnetic field strength and it was detectable even after XPS ion gun etching. Carbonation and nitridification of zinc thin films by sparking wires inside the magnetic field to observe the effect of the magnetic field on bandgap and chemical composition are confirmed by XPS.
The Effect of Weather and Location of Fruit within the Tree on the Incidence and Severity of Citrus Black Spot on Fruit
Authors: Hendricks Katherine E. , Christman Mary C. , Roberts Pamela D.
Published: January 2020

Citrus black spot (CBS) caused by the fungus Phyllosticta citricarpa occurs in tropical and sub-tropical citrus production regions and affects all varieties of citrus. In Florida, the disease cycle is unique, having only the asexual spore. This work examines incidence and severity of CBS (hard spot symptoms) on fruit in two citrus groves during 2013–2014, 2014–2015 (Grove III) and 2015–2016 (Grove II) citrus seasons. Disease incidence and severity on fruit were analyzed based on citrus season, side of tree evaluated, height within the canopy, tree health, and tree age. Results indicate an increase in CBS incidence in Grove III between 2013–2014 and 2014–2015 seasons, with more infected or symptomatic fruit on the road side of the canopy and a higher incidence above 2 meters. Tree health status affected incidence but not severity and tree age had a significant effect on severity of CBS in Grove II. Analysis of weather data conducive for infection, between 2010 and 2017, indicated an average of 172 days per year (range: 104–261 days) when the temperature (15–35 °C) and relative humidity (RH ≥ 90% for 8 consecutive hours) were conducive for infection of fruit and an average of 98 days per year (range: 72–123 days) when the fruit were susceptible to infection.
Publisher Correction: Activation of G-protein-gated inwardly rectifying potassium (Kir3/GirK) channels rescues hippocampal functions in a mouse model of early amyloid-β pathology
Authors: Sánchez-Rodríguez Irene , Temprano-Carazo Sara , Nájera Alberto , Djebari Souhail , Yajeya Javier , Gruart Agnès , Delgado-García José M. , Jiménez-Díaz Lydia , Navarro-López Juan D.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Estimation of minute ventilation by heart rate for field exercise studies
Authors: Cruz Ramon , Alves Danilo L. , Rumenig Eduardo , Gonçalves Renata , Degaki Edson , Pasqua Leonardo , Koch Sarah , Lima-Silva Adriano E. , S. Koehle Michael , Bertuzzi Romulo
Published: January 2020

The aim of this study was to develop predictive equations for minute ventilation based on heart rate, and to test the precision of the equations in two forms of endurance exercise. Eighteen men (age 27.8 ± 5.4 years old, maximal oxygen uptake 45.4 ± 8.3 ml·kg−1·min−1) performed a maximal progressive cycle test in which minute ventilation and heart rate were continually measured and further used to establish the proposed equations with quadratic and exponential adjustments. In the second and third laboratory visits, sixteen participants completed two cycling bouts, one high-intensity interval exercise and one low-intensity continuous exercise. The minute ventilation and heart rate were measured in both exercises and the validity of the equations tested. The Bland-Altman analysis showed agreement between the minute ventilation and estimated equations for interval and continuous exercise. There was no difference between the minute ventilation obtained from both equations and the minute ventilation directly measured during the interval exercise. However, the quadratic equation underestimated the minute ventilation during continuous exercise (p < 0.05). While both equations seem to be suitable to estimate minute ventilation during high-intensity interval exercise, the exponential equation is recommended for low-intensity continuous exercise.
Connecting biology, optics and nanomechanical properties in micro-wasps
Authors: Mora-Castro Rebeca , Hernández-Jiménez Marcela , Sáenz-Arce Giovanni , Porras-Peñaranda Juan , Hanson-Snortum Paul , Avendaño-Soto Esteban
Published: January 2020

Coloration in insects provides a fruitful opportunity for interdisciplinary research involving both physics and biology, and for a better understanding of the design principles of biological structures. In this research we used nanometric and micrometric analyses to investigate the morphological and mechanical properties of the black-orange-black (BOB) color pattern in scelionid wasps, which has never been studied. The primary objective of the present investigation was to explore the structural and mechanical differences in the mesoscutum of four species: Baryconus with an orange mesosoma (i.e. BOB pattern), all black Baryconus, Scelio with an orange mesosoma (i.e. BOB pattern), and all black Scelio. The most outstanding findings include the absence of multilayer structures that generate structural color, a pigment concentrated in the upper surface of the epicuticle, and surprising differences between the four species. Three of the four species showed an accordion-like structure in the furrow (notaulus), whereas the adjacent mesoscutum was different in each species. Moreover, the normalized color component spectra for blue, green and red colors of the black mesoscutum of each genus showed the same spectral dependence while the orange color manifested small changes in the dominant wavelength, resulting in slightly different orange tones.
Comparative study of the interactions between fungal transcription factor nuclear localization sequences with mammalian and fungal importin-alpha
Authors: Bernardes Natália E. , Fukuda Cintia A. , da Silva Tainá D. , de Oliveira Hamine C. , de Barros Andrea C. , Dreyer Thiago R. , Bertolini Maria Célia , Fontes Marcos R. M.
Published: January 2020

Importin-α (Impα) is an adaptor protein that binds to cargo proteins (containing Nuclear Localization Sequences - NLSs), for their translocation to the nucleus. The specificities of the Impα/NLS interactions have been studied, since these features could be used as important tools to find potential NLSs in nuclear proteins or even for the development of targets to inhibit nuclear import or to design peptides for drug delivery. Few structural studies have compared different Impα variants from the same organism or Impα of different organisms. Previously, we investigated nuclear transport of transcription factors with Neurospora crassa Impα (NcImpα). Herein, NIT-2 and PAC-3 transcription factors NLSs were studied in complex with Mus musculus Impα (MmImpα). Calorimetric assays demonstrated that the PAC-3 NLS peptide interacts with both Impα proteins with approximately the same affinity. The NIT-2 NLS sequence binds with high affinity to the Impα major binding site from both organisms, but its binding to minor binding sites reveals interesting differences due to the presence of additional interactions of NIT-2-NLS with MmImpα. These findings, together with previous results with Impα from other organisms, indicate that the differential affinity of NLSs to minor binding sites may be also responsible for the selectivity of some cargo proteins recognition and transport.
High quality 3C de novo assembly and annotation of a multidrug resistant ST-111 Pseudomonas aeruginosa genome: Benchmark of hybrid and non-hybrid assemblers
Authors: Molina-Mora José Arturo , Campos-Sánchez Rebeca , Rodríguez César , Shi Leming , García Fernando
Published: January 2020

Genotyping methods and genome sequencing are indispensable to reveal genomic structure of bacterial species displaying high level of genome plasticity. However, reconstruction of genome or assembly is not straightforward due to data complexity, including repeats, mobile and accessory genetic elements of bacterial genomes. Moreover, since the solution to this problem is strongly influenced by sequencing technology, bioinformatics pipelines, and selection criteria to assess assemblers, there is no systematic way to selecta priorithe optimal assembler and parameter settings. To assembly the genome ofPseudomonas aeruginosastrain AG1 (PaeAG1), short reads (Illumina) and long reads (Oxford Nanopore) sequencing data were used in 13 different non-hybrid and hybrid approaches. PaeAG1 is a multiresistant high-risk sequence type 111 (ST-111) clone that was isolated from a Costa Rican hospital and it was the first report of an isolate ofP. aeruginosacarrying both blaVIM-2 and blaIMP-18 genes encoding for metallo-β-lactamases (MBL) enzymes. To assess the assemblies, multiple metrics regard to contiguity, correctness and completeness (3C criterion, as we define here) were used for benchmarking the 13 approaches and select a definitive assembly. In addition, annotation was done to identify genes (coding and RNA regions) and to describe the genomic content of PaeAG1. Whereas long reads and hybrid approaches showed better performances in terms of contiguity, higher correctness and completeness metrics were obtained for short read only and hybrid approaches. A manually curated and polished hybrid assembly gave rise to a single circular sequence with 100% of core genes and known regions identified, >98% of reads mapped back, no gaps, and uniform coverage. The strategy followed to obtain this high-quality 3C assembly is detailed in the manuscript and we provide readers with an all-in-one script to replicate our results or to apply it to other troublesome cases. The final 3C assembly revealed that the PaeAG1 genome has 7,190,208 bp, a 65.7% GC content and 6,709 genes (6,620 coding sequences), many of which are included in multiple mobile genomic elements, such as 57 genomic islands, six prophages, and two complete integrons with blaVIM-2 and blaIMP-18 MBL genes. Up to 250 and 60 of the predicted genes are anticipated to play a role in virulence (adherence, quorum sensing and secretion) or antibiotic resistance (β-lactamases, efflux pumps, etc). Altogether, the assembly and annotation of the PaeAG1 genome provide new perspectives to continue studying the genomic diversity and gene content of this important human pathogen.
Mutual population-shift driven antibody-peptide binding elucidated by molecular dynamics simulations
Authors: Bekker Gert-Jan , Fukuda Ikuo , Higo Junichi , Kamiya Narutoshi
Published: January 2020

Antibody based bio-molecular drugs are an exciting, new avenue of drug development as an alternative to the more traditional small chemical compounds. However, the binding mechanism and the effect on the conformational ensembles of a therapeutic antibody to its peptide or protein antigen have not yet been well studied. We have utilized dynamic docking and path sampling simulations based on all-atom molecular dynamics to study the binding mechanism between the antibody solanezumab and the peptide amyloid-β (Aβ). Our docking simulations reproduced the experimental structure and gave us representative binding pathways, from which we accurately estimated the binding free energy. Not only do our results show why solanezumab has an explicit preference to bind to the monomeric form of Aβ, but that upon binding, both molecules are stabilized towards a specific conformation, suggesting that their complex formation follows a novel, mutual population-shift model, where upon binding, both molecules impact the dynamics of their reciprocal one.
Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer
Authors: Göthlin Eremo Anna , Lagergren Kajsa , Othman Lana , Montgomery Scott , Andersson Göran , Tina Elisabet
Published: January 2020

Breast cancer patients treated with tamoxifen may experience recurrence due to endocrine resistance, which highlights the need for additional predictive and prognostic biomarkers. The glyco-phosphoprotein osteopontin (OPN), encoded by the SPP1 gene, has previously shown to be associated with poor prognosis in breast cancer. However, studies on the predictive value of OPN are inconclusive. In the present study, we evaluated tissue SPP1 mRNA and OPN protein expression as markers of recurrence in estrogen receptor- positive (ER+) breast cancer tissue. Tamoxifen- treated patients with recurrence or non-recurrence were selected using a matched case-control design. SPP1 mRNA expression was analysed using qPCR (n = 100) and OPN protein by immunohistochemistry (n = 116) using different antibodies. Odds ratios were estimated with conditional logistic regression. The SPP1 expression increased the risk of recurrence with an odds ratio (OR) of 2.50 (95% confidence interval [CI]; 1.30–4.82), after adjustment for tumour grade, HER 2 status and other treatments to OR 3.62 (95% CI; 1.45–9.07). However, OPN protein expression was not associated with risk of recurrence or with SPP1-gene expression, suggesting SPP1 mRNA a stronger prognostic marker candidate compared to tumor tissue OPN protein.
Phlobaphenes modify pericarp thickness in maize and accumulation of the fumonisin mycotoxins
Authors: Landoni Michela , Puglisi Daniel , Cassani Elena , Borlini Giulia , Brunoldi Gloria , Comaschi Camilla , Pilu Roberto
Published: January 2020

Phlobaphenes are insoluble phenolic compounds which are accumulated in a limited number of tissues such as seed pericarp and cob glumes, conferring on them a typical red-brown pigmentation. These secondary metabolites, derived from 3-deoxy flavonoids, are thought to have an important role in plants’ resistance against various pathogens, e.g. by reducing fungal infection, and also to have beneficial effects on human and animal health due to their high antioxidant power. The aim of this work was to determine the role of phlobaphenes in reducing mycotoxin contamination on maize kernels. We analysed the effect of the P1 (pericarp color 1) gene on phlobaphenes accumulation, pericarp thickness and fumonisins accumulation. Analysing fumonisins accumulation in different genetic backgrounds through three seasons, we found a clear decrease of these toxins through the three years (Wilcoxon test, Z = 2.2, p = 0.0277) in coloured lines compared with the isogenic non-coloured ones. The coloured lines, carrying P1 allele showed an increase of phlobaphenes (about 10–14 fold) with respect to colourless lines. Furthermore there was a correlation between phlobaphenes accumulation and pericarp thickness (R = 0.9318; p = 0.0067). Taken together, these results suggest that the P1 gene plays a central role in regulating phlobaphenes accumulation in maize kernels, and indirectly, also tackles mycotoxins accumulation. The development and cultivation of corn varieties rich in phlobaphenes could be a powerful tool to reduce the loss of both quality and yield due to mycotoxin contamination, increasing the safety and the quality of the maize product.
Evaluation of PD-L1 and other immune markers in bladder urothelial carcinoma stratified by histologic variants and molecular subtypes
Authors: Li Huili , Zhang Qingzhao , Shuman Lauren , Kaag Matthew , Raman Jay D. , Merrill Suzanne , DeGraff David J. , Warrick Joshua I. , Chen Guoli
Published: January 2020

Although advanced bladder cancer overall has a poor prognosis, a subset of patients demonstrate durable response to immune checkpoint inhibitors. Evidence shows that the response to checkpoint inhibitors may be associated with type and degree of immune infiltration in the tumor microenvironment. Here, we evaluated immune markers stratified by molecular subtypes and histologic variants. The study utilized a series of urothelial carcinomas (UCs) by tissue microarray, on which histologic variants and molecular subtypes had previously been established. PD1, CD3, CD8 and CD68 expression was evaluated by immunohistochemistry in tumor infiltrating immune cells, while PD-L1 expression in the tumor microenvironment was assessed. Each marker was scored semi-quantitatively (score 0–3). Tumors were clustered by marker scores using agglomerative methods, and associations among markers, histologies, and molecular subtypes were analyzed. PD-L1 expression in the tumor microenvironment significantly correlated with presence of CD3, CD8 and chronic inflammation. Urothelial carcinoma may be classified as either immune high or low based on marker expression. The immune high group is enriched in higher CD3, PD-L1, and genomically-unstable molecular subtype, suggesting it may respond to checkpoint inhibitors. We also identified a degree of intratumoral heterogeneity in immune markers in bladder cancer.
Arctigenin inhibits prostate tumor growth in high-fat diet fed mice through dual actions on adipose tissue and tumor
Authors: Hao Qiongyu , Diaz Tanya , Verduzco Alejandro del Rio , Magyar Clara E. , Zhong Jin , Elshimali Yahya , Rettig Matthew B. , Henning Susanne M. , Vadgama Jaydutt V. , Wang Piwen
Published: January 2020

This study investigated the inhibitory effect of arctigenin, a novel anti-inflammatory lignan, on prostate cancer in obese conditions both in vitro and in vivo. In vitro obese models were established by co-culture of mouse adipocytes 3T3-L1 with androgen-sensitive LNCaP human prostate cancer cells, or by culturing LNCaP cells in adipocytes-conditioned medium. Arctigenin significantly inhibited LNCaP proliferation, along with decreased androgen receptor (AR) and increased Nkx3.1 cellular expression. Male severe combined immunodeficiency mice were subcutaneously implanted with human prostate cancer LAPC-4 xenograft tumors for in vivo study. Mice were fed high-fat (HF) diet and orally given arctigenin at 50 mg/kg body weight daily or vehicle control for 6 weeks. Tumor bearing HF control mice showed a significant increase in serum free fatty acids (FFAs) and decrease in subcutaneous/peritoneal fat depots compared to non-tumor bearing control mice. Arctigenin intervention significantly reduced tumor growth by 45%, associated with decreased circulating FFAs and adipokines/cytokines including IGF-1, VEGF, and MCP-1, along with decreased AR, Ki67, and microvessel density and increased Nkx3.1 expression in tumors. These results indicate the strong ability of arctigenin to co-target obesity and tumor itself in inhibition of prostate tumor growth at a lower concentration compared to most phytochemicals.
Association between maternal periodontal status and ultrasonographic measurement of fetal growth: A longitudinal study
Authors: Taniguchi-Tabata Ayano , Takeuchi Noriko , Uchida Yoko , Ekuni Daisuke , Morita Manabu
Published: January 2020

The aim of this prospective cohort study was to investigate the association between intrauterine fetal growth patterns and periodontal status in pregnant women. Fifty-three pregnant women were recruited. Periodontitis was diagnosed based on probing pocket depth and clinical attachment level. Maternal urinary 8-hydroxy-2’-deoxyguanosine levels and body mass index were recorded. Ultrasonographic measurements of the biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) were recorded, and estimated fetal weight (EFW) was calculated. In addition, approximation spline curves of BPD, AC, FL, and EFW were obtained throughout the gestation period. Recorded delivery outcomes were gestational age (GA), birth weight and length, sex, placental weight, and umbilical cord length. Forty-four participants (34.1 ± 4.9 years) were analyzed. Mean neonatal birth weight was 2906.0 ± 544.4 g. On multiple regression analysis, birth weight was related with periodontitis (standardized β = −0.21, P = 0.001). For EFW and BPD, the curves of the periodontitis group were located lower than those of the non-periodontitis group, with significant differences after 32 weeks and 20 weeks of GA, respectively. In conclusion, periodontal treatment before conception may be recommended and a good periodontal condition in the early stage of pregnancy at the latest is desirable for infant growth.
C-reactive protein and post-stroke depressive symptoms
Authors: Kowalska Katarzyna , Pasinska Paulina , Klimiec-Moskal Elzbieta , Pera Joanna , Slowik Agnieszka , Klimkowicz-Mrowiec Aleksandra , Dziedzic Tomasz
Published: January 2020

Our study aimed to explore the association between serum C-reactive protein (CRP) and post-stroke depressive symptoms. We prospectively recruited 572 patients with ischemic stroke or transient ischemic attack in whom serum CRP level was measured within 48 h after stroke onset. Depressive symptoms were assessed at day 8 and 3 months after stroke in 405 and 306 patients, respectively. Patients with greater depressive symptoms at day 8 and patients with greater depressive symptoms 3 months after stroke had higher CRP level (median: 7.9 vs 4.3 mg/L, P < 0.01 and 6.7 vs 3.4 mg/L, P = 0.01, respectively). In the univariate analysis, CRP > 9.2 mg/L was associated with depressive symptoms at day 8 (OR: 2.06, 95%CI: 1.30–3.28, P < 0.01) and CRP > 4.3 mg/L was associated with depressive symptoms 3 months after stroke (OR: 1.79, 95%CI: 1.06–3.02, P = 0.03). In the multivariate analysis, higher CRP level was related to depressive symptoms at day 8 (OR: 2.23, 95%CI: 1.28–3.90, P < 0.01), but not depressive symptoms 3 months after stroke (OR: 1.13, 95%CI: 0.59–2.17, P = 0.71). In conclusion, higher levels of CRP are associated with greater depressive symptoms at day 8 after stroke, but their effects on depressive symptoms 3 months after stroke are less significant.
Author Correction: ATAC-seq reveals alterations in open chromatin in pancreatic islets from subjects with type 2 diabetes
Authors: Bysani Madhusudhan , Agren Rasmus , Davegårdh Cajsa , Volkov Petr , Rönn Tina , Unneberg Per , Bacos Karl , Ling Charlotte
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Weakly encoded memories due to acute sleep restriction can be rescued after one night of recovery sleep
Authors: Baena Daniel , Cantero Jose L. , Fuentemilla Lluís , Atienza Mercedes
Published: January 2020

Sleep is thought to play a complementary role in human memory processing: sleep loss impairs the formation of new memories during the following awake period and, conversely, normal sleep promotes the strengthening of the already encoded memories. However, whether sleep can strengthen deteriorated memories caused by insufficient sleep remains unknown. Here, we showed that sleep restriction in a group of participants caused a reduction in the stability of EEG activity patterns across multiple encoding of the same event during awake, compared with a group of participants that got a full night’s sleep. The decrease of neural stability patterns in the sleep-restricted group was associated with higher slow oscillation-spindle coupling during a subsequent night of normal sleep duration, thereby suggesting the instantiation of restorative neural mechanisms adaptively supporting cognition and memory. Importantly, upon awaking, the two groups of participants showed equivalent retrieval accuracy supported by subtle differences in the reinstatement of encoding-related activity: it was longer lasting in sleep-restricted individuals than in controls. In addition, sustained reinstatement over time was associated with increased coupling between spindles and slow oscillations. Taken together, these results suggest that the strength of prior encoding might be an important moderator of memory consolidation during sleep. Supporting this view, spindles nesting in the slow oscillation increased the probability of correct recognition only for weakly encoded memories. Current results demonstrate the benefit that a full night’s sleep can induce to impaired memory traces caused by an inadequate amount of sleep.
Author Correction: Sensory primary cilium is a responsive cAMP microdomain in renal epithelia
Authors: Sherpa Rinzhin T. , Mohieldin Ashraf M. , Pala Rajasekharreddy , Wachten Dagmar , Ostrom Rennolds S. , Nauli Surya M.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Bridging the gap between measurements and modelling: a cardiovascular functional avatar
Authors: Casas Belén , Lantz Jonas , Viola Federica , Cedersund Gunnar , Bolger Ann F. , Carlhäll Carl-Johan , Karlsson Matts , Ebbers Tino
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Distinct neural mechanisms of social orienting and mentalizing revealed by independent measures of neural and eye movement typicality
Authors: Ramot Michal , Walsh Catherine , Reimann Gabrielle Elise , Martin Alex
Published: January 2020

Extensive study of typically developing individuals and those on the autism spectrum has identified a large number of brain regions associated with our ability to navigate the social world. Although it is widely appreciated that this so-called “social brain” is composed of distinct, interacting systems, these component parts have yet to be clearly elucidated. Here we used measures of eye movement and neural typicality—based on the degree to which subjects deviated from the norm—while typically developing (N = 62) and individuals with autism (N = 36) watched a large battery of movies depicting social interactions. Our findings provide clear evidence for distinct, but overlapping, neural systems underpinning two major components of the “social brain,” social orienting, and inferring the mental state of others.
Study of the intracellular nanoparticle-based radiosensitization mechanisms in F98 glioma cells treated with charged particle therapy through synchrotron-based infrared microspectroscopy
Authors: Martínez-Rovira I. , Seksek O. , Dokic I. , Brons S. , Abdollahi A. , Yousef I.
Published: January 2020

This work provides new insights into the molecular changes in response to nanoparticle-based radiotherapy treatments using ion beams through synchrotron-based infrared microspectroscopy.
Quantitative determination of titanium tetrachloride and dichloromethane by Raman spectroscopy using carbon disulfide as an internal standard
Authors: Xiang Xiaoyan , He Xianda , Xia Wentang , Yin Jianguo , Yuan Xiaoli , Zhou Xuejiao
Published: January 2020

Raman spectroscopy with an internal standard and peak height ratio was applied for the quantitative analysis of dichloromethane and titanium tetrachloride.
Facile synthesis of amorphous MoSx–Fe anchored on Zr-MOFs towards efficient and stable electrocatalytic hydrogen evolution
Authors: Zhang Le , Yan Zhenhua , Chen Xiang , Yu Meng , Liu Fangming , Cheng Fangyi , Chen Jun
Published: January 2020

MoSx–Fe nanoparticles dispersively, firmly anchored on a UiO-66-(OH)2 support via phenol–Fe(iii) coordination exhibit superior electrocatalytic hydrogen evolution performance in an acidic electrolyte.
Subtle sequence variations alter tripartite complex kinetics and G-quadruplex dynamics in RNA aptamer Broccoli
Authors: Savage Jonathan C. , Davare Monika A. , Shinde Ujwal
Published: January 2020

Spectroscopic and kinetic investigations of tripartite complex formation reveal differences between Broccoli and Spinach aptamers, highlighting how subtle sequence variations impart functional consequences of G-Quadruplex–cation interactions in RNA.
Vitamin-guanosine monophosphate conjugates for in vitro transcription priming
Authors: Papastavrou Nikolaos , Bande Omprakash , Marlière Philippe , Groaz Elisabetta , Herdewijn Piet
Published: January 2020

GMP-conjugates of two different vitamin precursors were synthesised and successfully incorporated into RNA.
The synthesis of sulfonated 4H-3,1-benzoxazines via an electro-chemical radical cascade cyclization
Authors: He Tian-Jun , Zhong Wei-Qiang , Huang Jing-Mei
Published: January 2020

We achieved sulfonated 4H-3,1-benzoxazines under ambient conditions without any metals and external chemical oxidants via electrochemical radical cascade cyclizations.
Ternary TiO2/SiOx@C nanocomposite derived from a novel titanium–silicon MOF for high-capacity and stable lithium storage
Authors: Shi Wenchao , Meng Jiashen , Li Qi , Xiao Zhitong , Xu Xiaoming , Qin Mingsheng , Zhang Xiao , Mai Liqiang
Published: January 2020

The all-in-one TiO2/SiOx@C derived from a novel titanium–silicon MOF exhibits enhanced lithium storage performance due to the unique ternary architecture.