bluuebunny/crossref_metadata_2025 huggingface dataset:
Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors
Authors: Guo Rongqun , Hu Fangxiao , Weng Qitong , Lv Cui , Wu Hongling , Liu Lijuan , Li Zongcheng , Zeng Yang , Bai Zhijie , Zhang Mengyun , Liu Yuting , Liu Xiaofei , Xia Chengxiang , Wang Tongjie , Zhou Peiqing , Wang Kaitao , Dong Yong , Luo Yuxuan , Zhang Xiangzhong , Guan Yuxian , Geng Yang , Du Juan , Li Yangqiu , Lan Yu , Chen Jiekai , Liu Bing , Wang Jinyong
Published: November 2019

Achievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells (PSCs) is a central aim in T cell regenerative medicine. To date, preferentially reconstituting T lymphopoiesis in vivo from PSCs remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial-to-hematopoietic transition and hematopoietic maturation stages in a PSC differentiation scheme (iR9-PSC) in vitro induced preferential generation of engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSCs, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The induced T cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis restored immune surveillance in immunodeficient mice. Furthermore, gene-edited iR9-PSCs produced tumor-specific T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T cells from the unlimited and editable PSC source.
Author Correction: Impacts of environmental and socio-economic factors on emergence and epidemic potential of Ebola in Africa
Authors: Redding David W. , Atkinson Peter M. , Cunningham Andrew A. , Iacono Gianni Lo , Moses Lina M. , Wood James L. N. , Jones Kate E.
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The indica nitrate reductase gene OsNR2 allele enhances rice yield potential and nitrogen use efficiency
Authors: Gao Zhenyu , Wang Yufeng , Chen Guang , Zhang Anpeng , Yang Shenglong , Shang Lianguang , Wang Danying , Ruan Banpu , Liu Chaolei , Jiang Hongzhen , Dong Guojun , Zhu Li , Hu Jiang , Zhang Guangheng , Zeng Dali , Guo Longbiao , Xu Guohua , Teng Sheng , Harberd Nicholas P. , Qian Qian
Published: November 2019

Theindicaandjaponicarice (Oryza sativa) subspecies differ in nitrate (NO3−) assimilation capacity and nitrogen (N) use efficiency (NUE). Here, we show that a major component of this difference is conferred by allelic variation atOsNR2, a gene encoding a NADH/NADPH-dependent NO3−reductase (NR). Selection-driven allelic divergence has resulted in variantindicaandjaponica OsNR2alleles encoding structurally distinct OsNR2 proteins, withindicaOsNR2 exhibiting greater NR activity.Indica OsNR2also promotes NO3−uptake via feed-forward interaction withOsNRT1.1B, a gene encoding a NO3−uptake transporter. These properties enableindica OsNR2to confer increased effective tiller number, grain yield and NUE onjaponicarice, effects enhanced by interaction with an additionally introgressedindica OsNRT1.1Ballele. In consequence,indica OsNR2provides an important breeding resource for the sustainable increases injaponicarice yields necessary for future global food security.
In-fibre particle manipulation and device assembly via laser induced thermocapillary convection
Authors: Zhang Jing , Wang Zhe , Wang Zhixun , Zhang Ting , Wei Lei
Published: November 2019

The ability to manipulate in-fibre particles is of technological and scientific significance, yet particle manipulation inside solid environment remains fundamentally challenging. Here we show an accurately controlled, non-contact, size- and material-independent method for manipulating in-fibre particles based on laser-induced thermocapillary convection. The laser liquefaction process transforms the fibre from a solid media into an ideal fluid environment and triggers the in-fibre thermocapillary convection. In-fibre particles, with diameter from submicron to hundreds of microns, can be migrated toward the designated position. The number of particles being migrated, the particle migration velocity and direction can be precisely controlled. As a proof-of-concept, the laser-induced flow currents lead to the migration-to-contact of dislocated in-fibre p- and n-type semiconductor particles and the forming of dual-particle p-n homo- and heterojunction directly in a fibre. This approach not only enables in-fibre device assembly to achieve multi-component fibre devices, but also provide fundamental insight for in-solid particle manipulation.
Cellular rescue in a zebrafish model of congenital muscular dystrophy type 1A
Authors: Hall T. E. , Wood A. J. , Ehrlich O. , Li M. , Sonntag C. S. , Cole N. J. , Huttner I. G. , Sztal T. E. , Currie P. D.
Published: November 2019

Laminins comprise structural components of basement membranes, critical in the regulation of differentiation, survival and migration of a diverse range of cell types, including skeletal muscle. Mutations in one muscle enriched Laminin isoform, Laminin alpha2 (Lama2), results in the most common form of congenital muscular dystrophy, congenital muscular dystrophy type 1A (MDC1A). However, the exact cellular mechanism by which Laminin loss results in the pathological spectrum associated with MDC1A remains elusive. Here we show, via live tracking of individual muscle fibres, that dystrophic myofibres in the zebrafish model of MDC1A maintain sarcolemmal integrity and undergo dynamic remodelling behaviours post detachment, including focal sarcolemmal reattachment, cell extension and hyper-fusion with surrounding myoblasts. These observations imply the existence of a window of therapeutic opportunity, where detached cells may be “re-functionalised” prior to their delayed entry into the cell death program, a process we show can be achieved by muscle specific or systemic Laminin delivery. We further reveal that Laminin also acts as a pro-regenerative factor that stimulates muscle stem cell-mediated repair in lama2-deficient animals in vivo. The potential multi-mode of action of Laminin replacement therapy suggests it may provide a potent therapeutic axis for the treatment for MDC1A.
Human mitochondrial DNA lineages in Iron-Age Fennoscandia suggest incipient admixture and eastern introduction of farming-related maternal ancestry
Authors: Översti Sanni , Majander Kerttu , Salmela Elina , Salo Kati , Arppe Laura , Belskiy Stanislav , Etu-Sihvola Heli , Laakso Ville , Mikkola Esa , Pfrengle Saskia , Putkonen Mikko , Taavitsainen Jussi-Pekka , Vuoristo Katja , Wessman Anna , Sajantila Antti , Oinonen Markku , Haak Wolfgang , Schuenemann Verena J. , Krause Johannes , Palo Jukka U. , Onkamo Päivi
Published: November 2019

Human ancient DNA studies have revealed high mobility in Europe’s past, and have helped to decode the human history on the Eurasian continent. Northeastern Europe, especially north of the Baltic Sea, however, remains less well understood largely due to the lack of preserved human remains. Finland, with a divergent population history from most of Europe, offers a unique perspective to hunter-gatherer way of life, but thus far genetic information on prehistoric human groups in Finland is nearly absent. Here we report 103 complete ancient mitochondrial genomes from human remains dated to AD 300–1800, and explore mtDNA diversity associated with hunter-gatherers and Neolithic farmers. The results indicate largely unadmixed mtDNA pools of differing ancestries from Iron-Age on, suggesting a rather late genetic shift from hunter-gatherers towards farmers in North-East Europe. Furthermore, the data suggest eastern introduction of farmer-related haplogroups into Finland, contradicting contemporary genetic patterns in Finns.
Data augmentation using generative adversarial networks (CycleGAN) to improve generalizability in CT segmentation tasks
Authors: Sandfort Veit , Yan Ke , Pickhardt Perry J. , Summers Ronald M.
Published: November 2019

Labeled medical imaging data is scarce and expensive to generate. To achieve generalizable deep learning models large amounts of data are needed. Standard data augmentation is a method to increase generalizability and is routinely performed. Generative adversarial networks offer a novel method for data augmentation. We evaluate the use of CycleGAN for data augmentation in CT segmentation tasks. Using a large image database we trained a CycleGAN to transform contrast CT images into non-contrast images. We then used the trained CycleGAN to augment our training using these synthetic non-contrast images. We compared the segmentation performance of a U-Net trained on the original dataset compared to a U-Net trained on the combined dataset of original data and synthetic non-contrast images. We further evaluated the U-Net segmentation performance on two separate datasets: The original contrast CT dataset on which segmentations were created and a second dataset from a different hospital containing only non-contrast CTs. We refer to these 2 separate datasets as the in-distribution and out-of-distribution datasets, respectively. We show that in several CT segmentation tasks performance is improved significantly, especially in out-of-distribution (noncontrast CT) data. For example, when training the model with standard augmentation techniques, performance of segmentation of the kidneys on out-of-distribution non-contrast images was dramatically lower than for in-distribution data (Dice score of 0.09 vs. 0.94 for out-of-distribution vs. in-distribution data, respectively, p < 0.001). When the kidney model was trained with CycleGAN augmentation techniques, the out-of-distribution (non-contrast) performance increased dramatically (from a Dice score of 0.09 to 0.66, p < 0.001). Improvements for the liver and spleen were smaller, from 0.86 to 0.89 and 0.65 to 0.69, respectively. We believe this method will be valuable to medical imaging researchers to reduce manual segmentation effort and cost in CT imaging.
Identification of candidate cancer drivers by integrative Epi-DNA and Gene Expression (iEDGE) data analysis
Authors: Li Amy , Chapuy Bjoern , Varelas Xaralabos , Sebastiani Paola , Monti Stefano
Published: November 2019

The emergence of large-scale multi-omics data warrants method development for data integration. Genomic studies from cancer patients have identified epigenetic and genetic regulators – such as methylation marks, somatic mutations, and somatic copy number alterations (SCNAs), among others – as predictive features of cancer outcome. However, identification of “driver genes” associated with a given alteration remains a challenge. To this end, we developed a computational tool, iEDGE, to model cis and trans effects of (epi-)DNA alterations and identify potential cis driver genes, where cis and trans genes denote those genes falling within and outside the genomic boundaries of a given (epi-)genetic alteration, respectively. iEDGE first identifies the cis and trans gene expression signatures associated with the presence/absence of a particular epi-DNA alteration across samples. It then applies tests of statistical mediation to determine the cis genes predictive of the trans gene expression. Finally, cis and trans effects are annotated by pathway enrichment analysis to gain insights into the underlying regulatory networks. We used iEDGE to perform integrative analysis of SCNAs and gene expression data from breast cancer and 18 additional cancer types included in The Cancer Genome Atlas (TCGA). Notably, cis gene drivers identified by iEDGE were found to be significantly enriched for known driver genes from multiple compendia of validated oncogenes and tumor suppressors, suggesting that the remainder are of equal importance. Furthermore, predicted drivers were enriched for functionally relevant cancer genes with amplification-driven dependencies, which are of potential prognostic and therapeutic value. All the analyses results are accessible at https://montilab.bu.edu/iEDGE. In summary, integrative analysis of SCNAs and gene expression using iEDGE successfully identified known cancer driver genes and putative cancer therapeutic targets across 19 cancer types in the TCGA. The proposed method can easily be applied to the integration of gene expression profiles with other epi-DNA assays in a variety of disease contexts.
Quantitative Multilayer Cu(410) Structure and Relaxation Determined by QLEED
Authors: Ahmed Rezwan , Makino Takamasa , Gueriba Jessiel Siaron , Mizuno Seigi , Diño Wilson Agerico , Okada Michio
Published: November 2019

Industrially relevant catalytically active surfaces exhibit defects. These defects serve as active sites; expose incoming adsorbates to both high and low coordinated surface atoms; determine morphology, reactivity, energetics, and surface relaxation. These, in turn, affect crystal growth, oxidation, catalysis, and corrosion. Systematic experimental analyses of such surface defects pose challenges, esp., when they do not exhibit order. High Miller index surfaces can provide access to these features and information, albeit indirectly. Here, we show that with quantitative low-energy electron diffraction (QLEED) intensity analyses and density functional theory (DFT) calculations, we can visualize the local atomic configuration, the corresponding electron distribution, and local reactivity. The QLEED-determined Cu(410) structure (Pendry reliability factor RP ≃ 0.0797) exhibits alternating sequences of expansion (+) and contraction (−) (of the first 16 atomic interlayers) relative to the bulk-truncated interlayer spacing of ca. 0.437 Å. The corresponding electron distribution shows smoothening relative to the bulk-determined structure. These results should aid us to further gain an atomic-scale understanding of the nature of defects in materials.
Contrast Induced Acute Kidney Injury and its Impact on Mid-Term Kidney Function, Cardiovascular Events and Mortality
Authors: Ribitsch Werner , Horina Joerg H. , Quehenberger Franz , Rosenkranz Alexander R. , Schilcher Gernot
Published: November 2019

The existence and clinical relevance of contrast induced acute kidney injury (CI-AKI) is still heavily debated and angiographic procedures are often withheld in fear of CI-AKI, especially in CKD-patients. We investigated the incidence of CI-AKI in cardiovascular high risk patients undergoing intra-arterial angiography and its impact on mid-term kidney function, cardiovascular events and mortality. We conducted a prospective observational trial on patients undergoing planned intra-arterial angiographic procedures. All subjects received standardized intravenous hydration prior to contrast application. CI-AKI was defined according to a ≥25% increase of creatinine from baseline to either 24hrs or 48hrs after angiography. Plasma creatinine and eGFR were recorded from the institutional medical record system one and three months after hospital discharge. Patients were followed up for two years to investigate the long term effects of CI-AKI on cardiovascular events and mortality. We studied 706 (317 female) patients with a mean eGFR of 52.0 ± 15 ml·min−1·1.73 m−2. The incidence of CI-AKI was 10.2% (72 patients). In 94 (13.3%) patients serum creatinine decreased ≥25% either 24 or 48 hours after angiography. Patients with CI-AKI had a lower creatinine and a higher eGFR at baseline, but no other independent predictors of CI-AKI could be identified. Kidney function was not different between both groups one and three months after discharge. After a two year follow up the overall incidence of cardiovascular events was 56.5% in the CI-AKI group and 58.8% in the Non CI-AKI group (p = 0.8), the incidence of myocardial infarctions, however, was higher in CI-AKI-patients. Overall survival was also not different between patients with CI-AKI (88.6%) and without CI-AKI (84.7%, p = 0.48). The occurrence of CI-AKI did not have any negative impact on mid-term kidney function, the incidence of cardiovascular events and mortality. Considerable fluctuations of serum creatinine interfere with the presumed diagnosis of CI-AKI. Necessary angiographic procedures should not be withheld in fear of CI-AKI.
Understanding controversies in the α-ω and ω-β phase transformations of zirconium from nonhydrostatic thermodynamics
Authors: Zhang Lin , Li Ying-Hua , Gu Yan-Qin , Cai Ling-Cang
Published: November 2019

Significant debate has been noted in the α-ω and ω-β phase transformations of zirconium. The initial pressure of the α-to-ω transformation at room temperature has been reported to vary from 0.25 to 7.0 GPa, while the hydrostatic transformation is believed to occur at approximately 2.2 GPa. Shear stress is commonly considered as a key factor leading to the discrepancy. However, the principal mechanisms previously proposed concluded that the phase transformation pressure would be decreased in the presence of shear stress. The experimental results of the α-ω transformation in zirconium are contrary to this conclusion. In the ω-β phase diagram of zirconium, the dT/dP along the phase boundary near the α-ω-β triple-point was reported to be either positive or negative, but no theoretical explanation, especially a quantitative one, has been proposed. This article aimed to quantitatively investigate and explain the controversies reported in the α-ω and ω-β phase transformations of zirconium by applying a new nonhydrostatic thermodynamic formalism for solid medium, which has recently been proposed and is capable of quantitatively estimating the impact of shear stress on phase transformations in solids.
High-throughput screening against protein:protein interaction interfaces reveals anti-cancer therapeutics as potent modulators of the voltage-gated Na+ channel complex
Authors: Wadsworth Paul A. , Folorunso Oluwarotimi , Nguyen Nghi , Singh Aditya K. , D’Amico Daniela , Powell Reid T. , Brunell David , Allen John , Stephan Clifford , Laezza Fernanda
Published: November 2019

Multiple voltage-gated Na+ (Nav) channelopathies can be ascribed to subtle changes in the Nav macromolecular complex. Fibroblast growth factor 14 (FGF14) is a functionally relevant component of the Nav1.6 channel complex, a causative link to spinocerebellar ataxia 27 (SCA27) and an emerging risk factor for neuropsychiatric disorders. Yet, how this protein:channel complex is regulated in the cell is still poorly understood. To search for key cellular pathways upstream of the FGF14:Nav1.6 complex, we have developed, miniaturized and optimized an in-cell assay in 384-well plates by stably reconstituting the FGF14:Nav1.6 complex using the split-luciferase complementation assay. We then conducted a high-throughput screening (HTS) of 267 FDA-approved compounds targeting known mediators of cellular signaling. Of the 65 hits initially detected, 24 were excluded based on counter-screening and cellular toxicity. Based on target analysis, potency and dose-response relationships, 5 compounds were subsequently repurchased for validation and confirmed as hits. Among those, the tyrosine kinase inhibitor lestaurtinib was highest ranked, exhibiting submicromolar inhibition of FGF14:Nav1.6 assembly. While providing evidence for a robust in-cell HTS platform that can be adapted to search for any channelopathy-associated regulatory proteins, these results lay the potential groundwork for repurposing cancer drugs for neuropsychopharmacology.
Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia
Authors: Henning Carina , Branopolski Anna , Schuler Dominik , Dimitroulis Dimitrios , Huelsemann Patrik , Nicolaus Christopher , Sansone Roberto , Ludolf Postma Jelle , Eberhard Daniel , Le Noble Ferdinand , Kelm Malte , Lammert Eckhard , Heiss Christian
Published: November 2019

An acute increase in blood flow triggers flow-mediated dilation (FMD), which is mainly mediated by endothelial nitric oxide synthase (eNOS). A long-term increase in blood flow chronically enlarges the arterial lumen, a process called arteriogenesis. In several common human diseases, these processes are disrupted for as yet unknown reasons. Here, we asked whether β1 integrin, a mechanosensory protein in endothelial cells, is required for FMD and arteriogenesis in the ischemic hindlimb. Permanent ligation of the femoral artery in C57BL/6 J mice enlarged pre-existing collateral arteries and increased numbers of arterioles in the thigh. In the lower leg, the numbers of capillaries increased. Notably, injection of β1 integrin-blocking antibody or tamoxifen-induced endothelial cell-specific deletion of the gene for β1 integrin (Itgb1) inhibited both arteriogenesis and angiogenesis. Using high frequency ultrasound, we demonstrated that β1 integrin-blocking antibody or endothelial cell-specific depletion of β1 integrin attenuated FMD of the femoral artery, and blocking of β1 integrin function did not further decrease FMD in eNOS-deficient mice. Our data suggest that endothelial β1 integrin is required for both acute and chronic widening of the arterial lumen in response to hindlimb ischemia, potentially via functional interaction with eNOS.
Micro-Crack Induced Buckypaper/PI Tape Hybrid Sensors with Enhanced and Tunable Piezo-Resistive Properties
Authors: Danish Mustafa , Luo Sida
Published: November 2019

Piezoresistive properties play a vital role in the development of sensor for structural health monitoring (SHM) applications. Novel stable crack initiation method (SCIM) is established to improve the gauge factor (GF) with maximum achievable working strain region for PI tape enabled buckypaper hybrid sensors. Cracks are generated by applying strain rate-controlled tension force using dynamic mechanical analyzer (DMA). The sensor has been cycled in tension to characterize GF with crack opening. It is determined experimentally that GF increases with increasing crack opening and crack becomes unstable when opening increases above 8 µm. Tremendous improvement in GF has been observed which improved from single-digit to several hundreds. The highest GF obtained so far is ~255, showing 75 times improvement compared with the ones without the SCIM implementation. The crack initiation strain (CIS) is characterized by sonication and centrifugation time. It is determined experimentally that the maximum CIS of 3.5% can be achieved with sonication time of 40 min and increasing centrifuge time has an in-significantly dropping effect on CIS. Excellent stability/reproducibility has been proved/demonstrated on SCIM implemented sensors through a rigorous 12,500 tensile cycle test on DMA. The performance of sensor is practically demonstrated in tension and bending on glass fiber reinforced polymer (GFRP) structures.
Structural insights into heme binding to IL-36α proinflammatory cytokine
Authors: Wißbrock Amelie , Goradia Nishit B. , Kumar Amit , Paul George Ajay Abisheck , Kühl Toni , Bellstedt Peter , Ramachandran Ramadurai , Hoffmann Patrick , Galler Kerstin , Popp Jürgen , Neugebauer Ute , Hampel Kornelia , Zimmermann Bastian , Adam Susanne , Wiendl Maximilian , Krönke Gerhard , Hamza Iqbal , Heinemann Stefan H. , Frey Silke , Hueber Axel J. , Ohlenschläger Oliver , Imhof Diana
Published: November 2019

Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.
The Relationship between Trial-by-Trial Variability and Oscillations of Cortical Population Activity
Authors: Daniel Edan , Meindertsma Thomas , Arazi Ayelet , Donner Tobias H. , Dinstein Ilan
Published: November 2019

Neural activity fluctuates over time, creating considerable variability across trials. This trial-by-trial neural variability is dramatically reduced (“quenched”) after the presentation of sensory stimuli. Likewise, the power of neural oscillations, primarily in the alpha-beta band, is also reduced after stimulus onset. Despite their similarity, these phenomena have so far been studied and discussed independently. We hypothesized that the two phenomena are tightly coupled in electrophysiological recordings of large cortical neural populations. To test this, we examined magnetoencephalography (MEG) recordings of healthy subjects viewing repeated presentations of a visual stimulus. The timing, amplitude, and spatial topography of variability-quenching and power-suppression were remarkably similar. Neural variability quenching was eliminated by excluding the alpha-beta band from the recordings, but not by excluding other frequency-bands. Moreover, individual magnitudes of alpha-beta band-power explained 86% of between-subject differences in variability quenching. An alternative mechanism that may generate variability quenching is increased phase alignment across trials. However, changes in inter-trial-phase-coherence (ITPC) exhibited distinct timing and no correlations with the magnitude of variability quenching in individual participants. These results reveal that neural variability quenching is tightly coupled with stimulus-induced changes in the power of alpha-beta band oscillations, associating two phenomena that have so far been studied in isolation.
Earthquake and typhoon trigger unprecedented transient shifts in shallow hydrothermal vents biogeochemistry
Authors: Lebrato Mario , Wang Yiming V. , Tseng Li-Chun , Achterberg Eric P. , Chen Xue-Gang , Molinero Juan-Carlos , Bremer Karen , Westernströer Ulrike , Söding Emanuel , Dahms Hans-Uwe , Küter Marie , Heinath Verena , Jöhnck Janika , Konstantinou Kostas I. , Yang Yiing J. , Hwang Jiang-Shiou , Garbe-Schönberg Dieter
Published: November 2019

Shallow hydrothermal vents are of pivotal relevance for ocean biogeochemical cycles, including seawater dissolved heavy metals and trace elements as well as the carbonate system balance. The Kueishan Tao (KST) stratovolcano off Taiwan is associated with numerous hydrothermal vents emitting warm sulfur-rich fluids at so-called White Vents (WV) and Yellow Vent (YV) that impact the surrounding seawater masses and habitats. The morphological and biogeochemical consequences caused by a M5.8 earthquake and a C5 typhoon (“Nepartak”) hitting KST (12th May, and 2nd–10th July, 2016) were studied within a 10-year time series (2009–2018) combining aerial drone imagery, technical diving, and hydrographic surveys. The catastrophic disturbances triggered landslides that reshaped the shoreline, burying the seabed and, as a consequence, native sulfur accretions that were abundant on the seafloor disappeared. A significant reduction in venting activity and fluid flow was observed at the high-temperature YV. Dissolved Inorganic Carbon (DIC) maxima in surrounding seawater reached 3000–5000 µmol kg−1, and Total Alkalinity (TA) drawdowns were below 1500–1000 µmol kg−1 lasting for one year. A strong decrease and, in some cases, depletion of dissolved elements (Cd, Ba, Tl, Pb, Fe, Cu, As) including Mg and Cl in seawater from shallow depths to the open ocean followed the disturbance, with a recovery of Mg and Cl to pre-disturbance concentrations in 2018. The WV and YV benthic megafauna exhibited mixed responses in their skeleton Mg:Ca and Sr:Ca ratios, not always following directions of seawater chemical changes. Over 70% of the organisms increased skeleton Mg:Ca ratio during rising DIC (higher CO2) despite decreasing seawater Mg:Ca ratios showing a high level of resilience. KST benthic organisms have historically co-existed with such events providing them ecological advantages under extreme conditions. The sudden and catastrophic changes observed at the KST site profoundly reshaped biogeochemical processes in shallow and offshore waters for one year, but they remained transient in nature, with a possible recovery of the system within two years.
CRISPR/Cas9-mediated editing of Δ5 and Δ6 desaturases impairs Δ8-desaturation and docosahexaenoic acid synthesis in Atlantic salmon (Salmo salar L.)
Authors: Datsomor Alex K. , Olsen Rolf E. , Zic Nikola , Madaro Angelico , Bones Atle M. , Edvardsen Rolf B. , Wargelius Anna , Winge Per
Published: November 2019

The in vivo functions of Atlantic salmon fatty acyl desaturases (fads2), Δ6fads2-a, Δ6fads2-b, Δ6fads2-c and Δ5fads2 in long chain polyunsaturated fatty acid (LC-PUFA) synthesis in salmon and fish in general remains to be elucidated. Here, we investigate in vivo functions and in vivo functional redundancy of salmon fads2 using two CRISPR-mediated partial knockout salmon, Δ6abc/5Mt with mutations in Δ6fads2-a, Δ6fads2-b, Δ6fads2-c and Δ5fads2, and Δ6bcMt with mutations in Δ6fads2-b and Δ6fads2-c. F0 fish displaying high degree of gene editing (50–100%) were fed low LC-PUFA and high LC-PUFA diets, the former containing reduced levels of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids but higher content of linoleic (18:2n-6) and alpha-linolenic (18:3n-3) acids, and the latter containing high levels of 20:5n-3 and 22:6n-3 but reduced compositions of 18:2n-6 and 18:3n-3. The Δ6abc/5Mt showed reduced 22:6n-3 levels and accumulated Δ6-desaturation substrates (18:2n-6, 18:3n-3) and Δ5-desaturation substrate (20:4n-3), demonstrating impaired 22:6n-3 synthesis compared to wildtypes (WT). Δ6bcMt showed no effect on Δ6-desaturation compared to WT, suggesting Δ6 Fads2-a as having the predominant Δ6-desaturation activity in salmon, at least in the tissues analyzed. Both Δ6abc/5Mt and Δ6bcMt demonstrated significant accumulation of Δ8-desaturation substrates (20:2n-6, 20:3n-3) when fed low LC-PUFA diet. Additionally, Δ6abc/5Mt demonstrated significant upregulation of the lipogenic transcription regulator, sterol regulatory element binding protein-1 (srebp-1) in liver and pyloric caeca under reduced dietary LC-PUFA. Our data suggest a combined effect of endogenous LC-PUFA synthesis and dietary LC-PUFA levels on srebp-1 expression which ultimately affects LC-PUFA synthesis in salmon. Our data also suggest Δ8-desaturation activities for salmon Δ6 Fads2 enzymes.
Exploring the limitations of biophysical propensity scales coupled with machine learning for protein sequence analysis
Authors: Raimondi Daniele , Orlando Gabriele , Vranken Wim F. , Moreau Yves
Published: November 2019

Machine learning (ML) is ubiquitous in bioinformatics, due to its versatility. One of the most crucial aspects to consider while training a ML model is to carefully select the optimal feature encoding for the problem at hand. Biophysical propensity scales are widely adopted in structural bioinformatics because they describe amino acids properties that are intuitively relevant for many structural and functional aspects of proteins, and are thus commonly used as input features for ML methods. In this paper we reproduce three classical structural bioinformatics prediction tasks to investigate the main assumptions about the use of propensity scales as input features for ML methods. We investigate their usefulness with different randomization experiments and we show that their effectiveness varies among the ML methods used and the tasks. We show that while linear methods are more dependent on the feature encoding, the specific biophysical meaning of the features is less relevant for non-linear methods. Moreover, we show that even among linear ML methods, the simpler one-hot encoding can surprisingly outperform the “biologically meaningful” scales. We also show that feature selection performed with non-linear ML methods may not be able to distinguish between randomized and “real” propensity scales by properly prioritizing to the latter. Finally, we show that learning problem-specific embeddings could be a simple, assumptions-free and optimal way to perform feature learning/engineering for structural bioinformatics tasks.
Steroid hormones in hair reveal sexual maturity and competition in wild house mice (Mus musculus domesticus)
Authors: Carlitz Esther H. D. , Runge Jan-Niklas , König Barbara , Winkler Lennart , Kirschbaum Clemens , Gao Wei , Lindholm Anna K.
Published: November 2019

Endocrine data from wild populations provide important insight into social systems. However, obtaining samples for traditional methods involves capture and restraint of animals, and/or pain, which can influence the animal’s stress level, and thereby undesirable release of hormones. Here, we measured corticosterone, testosterone and progesterone in the hair of 482 wild-derived house mice that experienced sexual competition while living under semi-natural conditions. We tested whether sex, age, weight and indicators of sexual maturity, reproduction and social conflicts predict hormone concentrations measured in hair (sampling at endpoint). We show that body weight, sex and age significantly predict cumulative testosterone and progesterone levels, allowing the differentiation between subadults and adults in both sexes. Corticosterone was only slightly elevated in older males compared to older females and increased with the level of visible injuries or scars. Testosterone in males positively correlated with body weight, age, testes size, and sperm number. Progesterone in females significantly increased with age, body weight, and the number of embryos implanted throughout life, but not with the number of litters when controlled for age and weight. Our results highlight the biological validity of hair steroid measurements and provide important insight into reproductive competition in wild house mice.
Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms
Authors: Basso Virginia , Tran Dat Q. , Schaal Justin B. , Tran Patti , Eriguchi Yoshihiro , Ngole Diana , Cabebe Anthony E. , Park A. young , Beringer Paul M. , Ouellette André J. , Selsted Michael E.
Published: November 2019

Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections in hospitalized and immunosuppressed patients. Mortality rates associated with these infections have risen sharply due to the emergence of multidrug resistant (MDR) strains of C. albicans and other Candida spp., highlighting the urgent need of new antifungal therapies. Rhesus theta (θ) defensin-1 (RTD-1), a natural macrocyclic antimicrobial peptide, was recently shown to be rapidly fungicidal against clinical isolates of MDR C. albicans in vitro. Here we found that RTD-1 was rapidly fungicidal against blastospores of fluconazole/caspofungin resistant C. albicans strains, and was active against established C. albicans biofilms in vitro. In vivo, systemic administration of RTD-1, initiated at the time of infection or 24 h post-infection, promoted long term survival in candidemic mice whether infected with drug-sensitive or MDR strains of C. albicans. RTD-1 induced an early (4 h post treatment) increase in neutrophils in naive and infected mice. In vivo efficacy was associated with fungal clearance, restoration of dysregulated inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-10, and IL-17, and homeostatic reduction in numbers of circulating neutrophils and monocytes. Because these effects occurred using peptide doses that produced maximal plasma concentrations (Cmax) of less than 1% of RTD-1 levels required for in vitro antifungal activity in 50% mouse serum, while inducing a transient neutrophilia, we suggest that RTD-1 mediates its antifungal effects in vivo by host directed mechanisms rather than direct fungicidal activity. Results of this study suggest that θ-defensins represent a new class of host-directed compounds for treatment of disseminated candidiasis.
Influence of the foveal curvature on myopic macular complications
Authors: Park Un Chul , Ma Dae Joong , Ghim Woon Hyung , Yu Hyeong Gon
Published: November 2019

In this cross-sectional study, we investigated whether a foveal curvature affects the development of two major myopic macular complications, myopic traction maculopathy (MTM) and myopic choroidal neovascularization (mCNV). In high myopic eyes (axial length ≥ 26.5 mm, refractive error ≤ −6 diopters) with posterior staphyloma, three different parameters of foveal curvature (staphyloma height, coefficient a, and curvature index) calculated based on the retinal pigment epithelium hyperreflective line in spectral domain optical coherence tomography image were compared among the MTM (72 eyes), mCNV (58 eyes), and control (69 eyes) group. The three curvature parameters showed a significant correlation with each other (all P’s < 0.001). The axial length, refractive error, and staphyloma types were comparable among the groups, but the means of all three curvature parameters were significantly greater in the MTM group compared to the mCNV and control groups (all P’s < 0.001). Furthermore, the curvature parameters had a significant correlation with myopic severity in the MTM group, but not in the other groups. These results suggest that a steeper change of foveal curvature plays a role in the development of MTM but not mCNV in high myopes.
Effects of global change factors and living roots on root litter decomposition in a Qinghai-Tibet alpine meadow
Authors: Shu Meng , Zhao Qingzhou , Li Zhen , Zhang Lin , Wang Peng , Hu Shuijin
Published: November 2019

Roots account for a major part of plant biomass in Tibetan alpine meadows. Understanding root decomposition with global change is key to predict carbon (C) and nutrient dynamics on the Qinghai-Tibet Plateau. Yet, few experiments have carefully examined root decomposition as influenced by global change. We conducted a field study to investigate the effects of nitrogen (N) addition, air warming, precipitation change, and the presence/absence of living roots on root decomposition in a Tibetan alpine meadow. Our results showed that N addition increased the mass and C remaining, and induced N accumulation in the litter. Increased precipitation significantly amplified the positive effect of N addition on litter mass remaining. The presence of alive roots in the litterbags decreased root litter C remaining but significantly increased N and phosphorus remaining of the litter. However, we did not find any significant effects of air warming on the litter decomposition. In the Qinghai-Tibet Plateau, N deposition is predicted to increase and precipitation regime is predicted to change. Our results suggest that the interaction between increased N and precipitation may reduce root decomposition in the Qinghai-Tibet Plateau in the future, and that the large stock of living roots exert a dominant impact on nutrient dynamics of root decomposition in the Tibetan alpine systems.
Retraction Note: Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism
Authors: Pratheeshkumar Poyil , Son Young-Ok , Divya Sasidharan Padmaja , Wang Lei , Zhang Zhuo , Shi Xianglin
Published: November 2019

This article has been retracted.
A common mechanism allows selective targeting of GluN2B subunit-containing N-methyl-D-aspartate receptors
Authors: Schreiber Julian A. , Schepmann Dirk , Frehland Bastian , Thum Simone , Datunashvili Maia , Budde Thomas , Hollmann Michael , Strutz-Seebohm Nathalie , Wünsch Bernhard , Seebohm Guiscard
Published: November 2019

N-methyl-D-aspartate receptors (NMDARs), especially GluN2B-containing NMDARs, are associated with neurodegenerative diseases like Parkinson, Alzheimer and Huntington based on their high Ca2+ conductivity. Overactivation leads to high intracellular Ca2+ concentrations and cell death rendering GluN2B-selective inhibitors as promising drug candidates. Ifenprodil represents the first highly potent prototypical, subtype-selective inhibitor of GluN2B-containing NMDARs. However, activity of ifenprodil on serotonergic, adrenergic and sigma receptors limits its therapeutic use. Structural reorganization of the ifenprodil scaffold to obtain 3-benzazepines retained inhibitory GluN2B activity but decreased the affinity at the mentioned non-NMDARs. While scaffold optimization improves the selectivity, the molecular inhibitory mechanism of these compounds is still not known. Here, we show a common inhibitory mechanism of ifenprodil and the related 3-benzazepines by mutational modifications of the receptor binding site, chemical modifications of the 3-benzazepine scaffold and subsequent in silico simulation of the inhibitory mechanism.
Alpha-synuclein is strategically positioned for afferent modulation of midbrain dopamine neurons and is essential for cocaine preference
Authors: Trubetckaia Olga , Lane Ariana E. , Qian Liping , Zhou Ping , Lane Diane A.
Published: November 2019

Alpha-synuclein (α-syn) is an abundant neuroprotein elevated in cocaine addicts, linked to drug craving, and recruited to axon terminals undergoing glutamatergic plasticity - a proposed mechanism for substance abuse. However, little is known about normal α-syn function or how it contributes to substance abuse. We show that α-syn is critical for preference of hedonic stimuli and the cognitive flexibility needed to change behavioral strategies, functions that are altered with substance abuse. Electron microscopic analysis reveals changes in α-syn targeting of ventral tegmental area axon terminals that is dependent upon the duration of cocaine exposure. The dynamic changes in presynaptic α-syn position it to control neurotransmission and fine-tune the complex afferent inputs to dopamine neurons, potentially altering functional dopamine output. Cocaine also increases postsynaptic α-syn where it is needed for normal ALIX function, multivesicular body formation, and cocaine-induced exosome release indicating potentially similar α-syn actions for vesicle release pre- and post-synaptically.
Study on the biochemical mechanisms of the micro-wave ablation treatment of lung cancer byex vivoconfocal Raman microspectral imaging
Authors: Song Dongliang , Chen Tianming , Wang Shuang , Chen Shilin , Li Heping , Yu Fan , Zhang Jingyuan , Zhang Zhe
Published: November 2019

Confocal micro-Raman imaging for the characterization of biochemical variations after lung cancer treatment by microwave ablation.
Optimization of sensors based on encapsulated algae for pesticide detection in water
Authors: Gosset Antoine , Oestreicher Víctor , Perullini Mercedes , Bilmes Sara A. , Jobbágy Matías , Dulhoste Sophie , Bayard Rémy , Durrieu Claude
Published: November 2019

Pesticides represent a significant source of contamination for urban and suburban surface, ground and seawaters.
A study on the effect of synthetic α-to-β3-amino acid mutations on the binding of phosphopeptides to 14-3-3 proteins
Authors: Andrei Sebastian A. , Thijssen Vito , Brunsveld Luc , Ottmann Christian , Milroy Lech-Gustav
Published: November 2019

Systematic α → β3 amino acid substitutions reveal a crucial role for native +2 proline residues in 14-3-3 binding peptides.
Interaction of monomeric and self-assembled aromatic amino acids with model membranes: self-reproduction phenomena
Authors: Kanti De Soumya , Chakraborty Anjan
Published: November 2019

The spontaneous formation of amyloid structures of proteins is responsible for several major human neurodegenerative diseases.
Catalyst-free electrochemical decarboxylative cross-coupling of N-hydroxyphthalimide esters and N-heteroarenes towards C(sp3)–C(sp2) bond formation
Authors: Liu Yichang , Xue Liwei , Shi Biyin , Bu Faxiang , Wang Dan , Lu Lijun , Shi Renyi , Lei Aiwen
Published: November 2019

We formed C(sp3)–C(sp2) bonds under electrochemical conditions by using NHP esters and N-heteroarenes without any catalysts. Our approach could be a complement to the Kolbe reaction and a promising strategy for finding more new reactions.
Crystal aggregation into periodically grating-banded assemblies in phthalic acid modulated by molten poly(ethylene oxide)
Authors: Chen Tzu-Yu , Woo Eamor M. , Nagarajan Selvaraj
Published: November 2019

A small-molecule compound, phthalic acid (PA), crystallized in the presence of poly(ethylene oxide) (PEO) with various compositions was utilized as a model to investigate the morphology and crystal assembly of periodically ordered structures in banded spherulites.
Initial sampling in symmetrical quasiclassical dynamics based on Li–Miller mapping Hamiltonian
Authors: Zheng Jie , Xie Yu , Jiang Shengshi , Long Yunze , Ning Xin , Lan Zhenggang
Published: November 2019

A symmetrical quasiclassical (SQC) dynamics approach based on the Li–Miller (LM) mapping Hamiltonian (SQC-LM) was employed to describe nonadiabatic dynamics.
Thermodynamic and structural aspects of the aqueous uranium(iv) system – hydrolysisvs.sulfate complexation
Authors: Lehmann Susanne , Foerstendorf Harald , Zimmermann Thomas , Patzschke Michael , Bok Frank , Brendler Vinzenz , Stumpf Thorsten , Steudtner Robin
Published: November 2019

The aquatic speciation of U(iv) in acidic sulfate solution were studied by optical spectroscopy, quantum-chemical calculations, and thermodynamic modelling.
Transforming the carbon economy: challenges and opportunities in the convergence of low-cost electricity and reductive CO2 utilization
Authors: Grim R. Gary , Huang Zhe , Guarnieri Michael T. , Ferrell Jack R. , Tao Ling , Schaidle Joshua A.
Published: November 2019

Renewable electricity can be leveraged to produce fuels and chemicals from CO2, offering sustainable routes to reduce the carbon intensity of our energy and products-driven economy.
Atomic interface effect of a single atom copper catalyst for enhanced oxygen reduction reactions
Authors: Jiang Zhuoli , Sun Wenming , Shang Huishan , Chen Wenxing , Sun Tingting , Li Haijing , Dong Juncai , Zhou Jing , Li Zhi , Wang Yu , Cao Rui , Sarangi Ritimukta , Yang Zhengkun , Wang Dingsheng , Zhang Jiatao , Li Yadong
Published: November 2019

By the in situ X-ray absorption results, the gradually decrease of Cu oxidation state under applied potential implied that low-valence Cu (+1) species in the atomic interface of Cu–N4–C8S2 may work as the catalytic sites during an ORR process.
Microfluidic system forCaenorhabditis elegansculture and oxygen consumption rate measurements
Authors: Krenger Roger , Cornaglia Matteo , Lehnert Thomas , Gijs Martin A. M.
Published: November 2019

MicrofluidicC. elegansculture chamber with integrated oxygen sensing.
Molecular structures, and optical and magnetic properties of free-base tetrapyrazinoporphyrazine in various reduction states
Authors: Konarev Dmitri V. , Faraonov Maxim A. , Kuzmin Alexey V. , Osipov Nikita G. , Khasanov Salavat S. , Otsuka Akihiro , Yamochi Hideki , Kitagawa Hiroshi , Lyubovskaya Rimma N.
Published: November 2019

The synthesis, and spectral and structural characterization of the novel radical anion and dianion salts of free-base tetrapyrazinoporphyrazine (H2TPyzPz) as well as studies of their magnetic properties have been described.
A DFT study on the mechanism and origins of the ligand-controlled regioselectivity of a palladium-catalyzed dearomatic reaction of 1-(chloromethyl)naphthalene with phenylacetonitrile
Authors: Yu Binbin , Ling Menghang , Xie Hujun
Published: November 2019

DFT calculations demonstrated that the bulky ligand tBuPPh2 generates para-substituted products, while the small ligand Me2PPh provides ortho-substituted products.