bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant Biologically Mediated CO2 Uptake in the Pacific Arctic During the Late Open Water Season
Authors: Juranek L. , Takahashi T. , Mathis J. , Pickart R. 
Published: January 2019

AbstractShifting baselines in the Arctic atmosphere‐sea ice‐ocean system have significant potential to alter biogeochemical cycling and ecosystem dynamics. In particular, the impact of increased open water duration on lower trophic level productivity and biological CO2 sequestration is poorly understood. Using high‐resolution observations of surface seawater dissolved O2/Ar and pCO2 collected in the Pacific Arctic in October 2011 and 2012, we evaluate spatial variability in biological metabolic status (autotrophy vs heterotrophy) as constrained by O2/Ar saturation (∆O2/Ar) as well as the relationship between net biological production and the sea‐air gradient of pCO2 (∆pCO2). We find a robust relationship between ∆pCO2 and ∆O2/Ar (correlation coefficient of −0.74 and −0.61 for 2011 and 2012, respectively), which suggests that biological production in the late open water season is an important determinant of the air‐sea CO2 gradient at a timeframe of maximal ocean uptake for CO2 in this region. Patchiness in biological production as indicated by ∆O2/Ar suggests spatially variable nutrient supply mechanisms supporting late season growth amidst a generally strongly stratified and nutrient‐limited condition.
Gene expression, proteome and calcium signaling alterations in immortalized hippocampal astrocytes from an Alzheimer’s disease mouse model
Authors: Rocchio Francesca , Tapella Laura , Manfredi Marcello , Chisari Mariangela , Ronco Francesca , Ruffinatti Federico Alessandro , Conte Eleonora , Canonico Pier Luigi , Sortino Maria Angela , Grilli Mariagrazia , Marengo Emilio , Genazzani Armando A. , Lim Dmitry 
Published: January 2019

AbstractEvidence is rapidly growing regarding a role of astroglial cells in the pathogenesis of Alzheimer’s disease (AD), and the hippocampus is one of the important brain regions affected in AD. While primary astroglial cultures, both from wild-type mice and from rodent models of AD, have been useful for studying astrocyte-specific alterations, the limited cell number and short primary culture lifetime have limited the use of primary hippocampal astrocytes. To overcome these limitations, we have now established immortalized astroglial cell lines from the hippocampus of 3xTg-AD and wild-type control mice (3Tg-iAstro and WT-iAstro, respectively). Both 3Tg-iAstro and WT-iAstro maintain an astroglial phenotype and markers (glutamine synthetase, aldehyde dehydrogenase 1 family member L1 and aquaporin-4) but display proliferative potential until at least passage 25. Furthermore, these cell lines maintain the potassium inward rectifying (Kir) current and present transcriptional and proteomic profiles compatible with primary astrocytes. Importantly, differences between the 3Tg-iAstro and WT-iAstro cell lines in terms of calcium signaling and in terms of transcriptional changes can be re-conducted to the changes previously reported in primary astroglial cells. To illustrate the versatility of this model we performed shotgun mass spectrometry proteomic analysis and found that proteins related to RNA binding and ribosome are differentially expressed in 3Tg-iAstro vs WT-iAstro. In summary, we present here immortalized hippocampal astrocytes from WT and 3xTg-AD mice that might be a useful model to speed up research on the role of astrocytes in AD.
Differential roles of TNFα-TNFR1 and TNFα-TNFR2 in the differentiation and function of CD4+Foxp3+ induced Treg cells in vitro and in vivo periphery in autoimmune diseases
Authors: Yang Sujuan , Xie Chichu , Chen Ye , Wang Julie , Chen Xiaoqing , Lu Zhengqi , June Rayford R. , Zheng Song Guo 
Published: January 2019

AbstractTumor Necrosis Factor (TNF) α is a multifunctional cytokine with pro-inflammatory and anti-inflammatory characteristics. Increasing evidence suggests that thymus-derived, natural regulatory T cells (nTreg) express a remarkably high level of TNF Receptor 2 (TNFR2) and TNFα modulates the number or function of nTreg via TNFR2 in autoimmune diseases. Nonetheless, Treg cells consist of at least nTreg and iTreg that are induced in the periphery or in vitro and two subsets may have different biological characteristics. However, the role of TNF-TNFR signaling in development and function of these iTreg cells is less clear. In this study, we systemically studied the effect of TNFα and its receptor signals on iTreg differentiation, proliferation, and function in vitro and in vivo. We further investigated the expression and requirement of TNFR1 or TNFR2 expression on iTreg by utilizing TNFR1−/− and TNFR2−/− mice. We found that exogenous TNFα facilitated iTreg differentiation and function in vitro. TNFR2 deficiency hampered iTreg differentiation, proliferation, and function, while TNFR1 deficiency decreased the differentiation of inflammatory T cells such as Th1 and Th17 cells but maintained the regulatory capabilities of iTreg both in vitro and in vivo. Using colitis model, we also revealed TNFR2 but not TNFR1 deficiency compromised the iTreg functionality. Interestingly, inflammation affects TNFR expression on nTreg but not iTreg subset. Our results demonstrate that exogenous TNFα may enhance the differentiation and function of iTreg via TNFR2 signaling. The expression of TNFR2 on Treg might be downregulated in some autoimmune diseases, accompanied by an increased level of TNFR1. Thus, TNFR2 agonists or TNFR1-specific antagonists hold a potential promise for clinical application in treating patients with autoimmune diseases.
MCPIP1 regulates the sensitivity of pancreatic beta-cells to cytokine toxicity
Authors: Tyka Karolina , Jörns Anne , Turatsinze Jean-Valery , Eizirik Decio L. , Lenzen Sigurd , Gurgul-Convey Ewa 
Published: January 2019

AbstractThe autoimmune-mediated beta-cell death in type 1 diabetes (T1DM) is associated with local inflammation (insulitis). We examined the role of MCPIP1 (monocyte chemotactic protein–induced protein 1), a novel cytokine-induced antiinflammatory protein, in this process. Basal MCPIP1 expression was lower in rat vs. human islets and beta-cells. Proinflammatory cytokines stimulated MCPIP1 expression in rat and human islets and in insulin-secreting cells. Moderate overexpression of MCPIP1 protected insulin-secreting INS1E cells against cytokine toxicity by a mechanism dependent on the presence of the PIN/DUB domain in MCPIP1. It also reduced cytokine-induced Chop and C/ebpβ expression and maintained MCL-1 expression. The shRNA-mediated suppression of MCPIP1 led to the potentiation of cytokine-mediated NFκB activation and cytokine toxicity in human EndoC-βH1 beta-cells. MCPIP1 expression was very high in infiltrated beta-cells before and after diabetes manifestation in the LEW.1AR1-iddm rat model of human T1DM. The extremely high expression of MCPIP1 in clonal beta-cells was associated with a failure of the regulatory feedback-loop mechanism, ER stress induction and high cytokine toxicity. In conclusion, our data indicate that the expression level of MCPIP1 affects the susceptibility of insulin-secreting cells to cytokines and regulates the mechanism of beta-cell death in T1DM.
Indispensable role of the Ubiquitin-fold modifier 1-specific E3 ligase in maintaining intestinal homeostasis and controlling gut inflammation
Authors: Cai Yafei , Zhu Guangxun , Liu Siyang , Pan Zezheng , Quintero Michaela , Poole Candace J. , Lu Chunwan , Zhu Huabin , Islam Bianca , Riggelen Jan van , Browning Darren , Liu Kebin , Blumberg Richard , Singh Nagendra , Li Honglin 
Published: January 2019

AbstractIntestinal exocrine secretory cells, including Paneth and goblet cells, have a pivotal role in intestinal barrier function and mucosal immunity. Dysfunction of these cells may lead to the pathogenesis of human diseases such as inflammatory bowel disease (IBD). Therefore, identification and elucidation of key molecular mechanisms that regulate the development and function of these exocrine cells would be crucial for understanding of disease pathogenesis and discovery of new therapeutic targets. The Ufm1 conjugation system is a novel ubiquitin-like modification system that consists of Ufm1 (Ubiquitin modifier 1), Uba5 (Ufm1-activating enzyme, E1), Ufc1 (Ufm1-conjugating enzyme, E2) and poorly characterized Ufm1 E3 ligase(s). Recent mouse genetic studies have demonstrated its indispensable role in embryonic development and hematopoiesis. Yet its role in other tissues and organs remains poorly defined. In this study, we found that both Ufl1 and Ufbp1, two key components of the Ufm1 E3 ligase, were highly expressed in the intestinal exocrine cells. Ablation of either Ufl1 and Ufbp1 led to significant loss of both Paneth and goblet cells, which in turn resulted in dysbiotic microbiota and increased susceptibility to experimentally induced colitis. At the cellular and molecular levels, Ufbp1 deficiency caused elevation of endoplasmic reticulum stress and activation of the Unfolded Protein Response (UPR) and cell death program. Administration of small molecular chaperone partially prevented loss of Paneth cells caused by acute Ufbp1 deletion. Taken together, our results have provided unambiguous evidence for the crucial role of the Ufm1 E3 ligase in maintenance of intestinal homeostasis and protection from inflammatory diseases.
The metacaspase Yca1 maintains proteostasis through multiple interactions with the ubiquitin system
Authors: Shrestha Amit , Brunette Steve , Stanford William Lloyd , Megeney Lynn Arthur 
Published: January 2019

AbstractMetacaspase enzymes are critical regulatory factors that paradoxically engage apoptosis and also maintain cell viability. For example, the Saccharomyces cerevisiae metacaspase Yca1 has been shown to be important for maintaining cellular proteostasis during stress, and the loss of this enzyme results in increased retention of aggregated material within the insoluble proteome. However, the molecular mechanism(s) by which Yca1 maintains cellular proteostasis remains unknown. Here, using proteomic analysis coupled with protein interaction studies we identified a direct interplay between Yca1 and the ubiquitin-proteasome system. We noted multiple ubiquitination sites on Yca1 and established Rsp5 as the candidate E3 ligase involved in this process. Further characterization of the ubiquitination sites identified the K355 residue on Yca1 as a critical modification for proteostasis function, managing both insoluble protein content and vacuolar response. We also identified a Yca1 phosphorylation site at S346, which promoted interaction with Rsp5 and the aggregate dispersal function of the metacaspase. Interestingly, proteomic analysis also revealed that Yca1 interacts with the ubiquitin precursor protein Rps31, cleaving the protein to release free ubiquitin. In turn, loss of Yca1 or its catalytic activity reduced the levels of monomeric ubiquitin in vivo, concurrent to increased protein aggregation. The K355 and S346 residues were also observed to influence the abundance of low-molecular weight ubiquitin. Together, these observations suggest that Yca1 maintains proteostasis and limits protein aggregation by ensuring a free flow of monoubiquitin, an essential precursor for ligase-enhanced Yca1 enzymatic activity and general proteasome-mediated protein degradation.
Somatosensory alpha oscillations gate perceptual learning efficiency
Authors: Brickwedde Marion , Krüger Marie C. , Dinse Hubert R. 
Published: January 2019

AbstractCognition and perception are closely coupled to alpha power, but whether there is a link between alpha power and perceptual learning efficacy is unknown. Here we show that somatosensory alpha power can be successfully up- and down-regulated with short-term neurofeedback training, which in turn controls subsequent tactile perceptual learning. We find that neurofeedback-induced increases in alpha power lead to enhanced learning, whereas reductions in alpha power impede learning. As a consequence, interindividual learning variability is substantially reduced. No comparable impact is observed for oscillatory power in theta, beta, and lower gamma frequency bands. Our results demonstrate that high pre-learning alpha levels are a requirement for reaching high learning efficiency. These data provide further evidence that alpha oscillations shape the functional architecture of the brain network by gating neural resources and thereby modulating levels of preparedness for upcoming processing.
In-situ formation of one-dimensional coordination polymers
in molecular junctions
Authors: Vladyka Anton , Perrin Mickael L. , Overbeck Jan , Ferradás Rubén R. , García-Suárez Víctor , Gantenbein Markus , Brunner Jan , Mayor Marcel , Ferrer Jaime , Calame Michel 
Published: January 2019

AbstractWe demonstrate the bottom-up in-situ formation of organometallic
oligomer chains at the single-molecule level. The chains are formed using the
mechanically controllable break junction technique operated in a liquid environment,
and consist of alternating isocyano-terminated benzene monomers coordinated to gold
atoms. We show that the chaining process is critically determined by the surface
density of molecules. In particular, we demonstrate that by reducing the local
supply of molecules within the junction, either by lowering the molecular
concentration or by adding side groups, the oligomerization process can be
suppressed. Our experimental results are supported by ab-initio simulations,
confirming that the isocyano terminating groups display a high tendency to form
molecular chains, as a result of their high affinity for gold. Our findings open the
road for the controlled formation of one-dimensional, single coordination-polymer
chains as promising model systems of organometallic frameworks.
Higher order effects in organic LEDs with sub-bandgap turn-on
Authors: Engmann Sebastian , Barito Adam J. , Bittle Emily G. , Giebink Noel C. , Richter Lee J. , Gundlach David J. 
Published: January 2019

AbstractSpin-dependent nonlinear processes in organic materials such as singlet-fission and triplet-triplet annihilation could increase the performance for photovoltaics, detectors, and light emitting diodes. Rubrene/C60 light emitting diodes exhibit a distinct low voltage (half-bandgap) threshold for emission. Two origins for the low voltage turn-on have been proposed: (i) Auger assisted energy up-conversion, and (ii) triplet-triplet annihilation. We test these proposals by systematically altering the rubrene/C60 interface kinetics by introducing thin interlayers. Quantitative analysis of the unmodified rubrene/C60 device suggests that higher order processes can be ruled out as the origin of the sub-bandgap turn-on. Rather, band-to-band recombination is the most likely radiative recombination process. However, insertion of a bathocuproine layer yields a 3-fold increase in luminance compared to the unmodified device. This indicates that suppression of parasitic interface processes by judicious modification of the interface allows a triplet-triplet annihilation channel to be observed.
Approximate Bayesian computation with deep learning supports a third archaic introgression in Asia and Oceania
Authors: Mondal Mayukh , Bertranpetit Jaume , Lao Oscar 
Published: January 2019

AbstractSince anatomically modern humans dispersed Out of Africa, the evolutionary history of Eurasian populations has been marked by introgressions from presently extinct hominins. Some of these introgressions have been identified using sequenced ancient genomes (Neanderthal and Denisova). Other introgressions have been proposed for still unidentified groups using the genetic diversity present in current human populations. We built a demographic model based on deep learning in an Approximate Bayesian Computation framework to infer the evolutionary history of Eurasian populations including past introgression events in Out of Africa populations fitting the current genetic evidence. In addition to the reported Neanderthal and Denisovan introgressions, our results support a third introgression in all Asian and Oceanian populations from an archaic population. This population is either related to the Neanderthal-Denisova clade or diverged early from the Denisova lineage. We propose the use of deep learning methods for clarifying situations with high complexity in evolutionary genomics.
Early preclinical detection of prions in the skin of prion-infected animals
Authors: Wang Zerui , Manca Matteo , Foutz Aaron , Camacho Manuel V. , Raymond Gregory J. , Race Brent , Orru Christina D. , Yuan Jue , Shen Pingping , Li Baiya , Lang Yue , Dang Johnny , Adornato Alise , Williams Katie , Maurer Nicholas R. , Gambetti Pierluigi , Xu Bin , Surewicz Witold , Petersen Robert B. , Dong Xiaoping , Appleby Brian S. , Caughey Byron , Cui Li , Kong Qingzhong , Zou Wen-Quan 
Published: January 2019

AbstractA definitive pre-mortem diagnosis of prion disease depends on brain biopsy for prion detection currently and no validated alternative preclinical diagnostic tests have been reported to date. To determine the feasibility of using skin for preclinical diagnosis, here we report ultrasensitive serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays of skin samples from hamsters and humanized transgenic mice (Tg40h) at different time points after intracerebral inoculation with 263K and sCJDMM1 prions, respectively. sPMCA detects skin PrPSc as early as 2 weeks post inoculation (wpi) in hamsters and 4 wpi in Tg40h mice; RT-QuIC assay reveals earliest skin prion-seeding activity at 3 wpi in hamsters and 20 wpi in Tg40h mice. Unlike 263K-inoculated animals, mock-inoculated animals show detectable skin/brain PrPSc only after long cohabitation periods with scrapie-infected animals. Our study provides the proof-of-concept evidence that skin prions could be a biomarker for preclinical diagnosis of prion disease.
Non defect-stabilized thermally stable single-atom catalyst
Authors: Lang Rui , Xi Wei , Liu Jin-Cheng , Cui Yi-Tao , Li Tianbo , Lee Adam Fraser , Chen Fang , Chen Yang , Li Lei , Li Lin , Lin Jian , Miao Shu , Liu Xiaoyan , Wang Ai-Qin , Wang Xiaodong , Luo Jun , Qiao Botao , Li Jun , Zhang Tao 
Published: January 2019

AbstractSurface-supported isolated atoms in single-atom catalysts (SACs) are usually stabilized by diverse defects. The fabrication of high-metal-loading and thermally stable SACs remains a formidable challenge due to the difficulty of creating high densities of underpinning stable defects. Here we report that isolated Pt atoms can be stabilized through a strong covalent metal-support interaction (CMSI) that is not associated with support defects, yielding a high-loading and thermally stable SAC by trapping either the already deposited Pt atoms or the PtO2units vaporized from nanoparticles during high-temperature calcination. Experimental and computational modeling studies reveal that iron oxide reducibility is crucial to anchor isolated Pt atoms. The resulting high concentrations of single atoms enable specific activities far exceeding those of conventional nanoparticle catalysts. This non defect-stabilization strategy can be extended to non-reducible supports by simply doping with iron oxide, thus paving a new way for constructing high-loading SACs for diverse industrially important catalytic reactions.
Half-quantum vortices and walls bounded by strings in the polar-distorted phases of topological superfluid 3He
Authors: Mäkinen J. T. , Dmitriev V. V. , Nissinen J. , Rysti J. , Volovik G. E. , Yudin A. N. , Zhang K. , Eltsov V. B. 
Published: January 2019

AbstractSymmetries of the physical world have guided formulation of fundamental laws, including relativistic quantum field theory and understanding of possible states of matter. Topological defects (TDs) often control the universal behavior of macroscopic quantum systems, while topology and broken symmetries determine allowed TDs. Taking advantage of the symmetry-breaking patterns in the phase diagram of nanoconfined superfluid 3He, we show that half-quantum vortices (HQVs)—linear topological defects carrying half quantum of circulation—survive transitions from the polar phase to other superfluid phases with polar distortion. In the polar-distorted A phase, HQV cores in 2D systems should harbor non-Abelian Majorana modes. In the polar-distorted B phase, HQVs form composite defects—walls bounded by strings hypothesized decades ago in cosmology. Our experiments establish the superfluid phases of 3He in nanostructured confinement as a promising topological media for further investigations ranging from topological quantum computing to cosmology and grand unification scenarios.
A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
Authors: Luo Xiao , Qian Liujia , Xiao Yansheng , Tang Yao , Zhao Yang , Wang Xia , Gu Luyan , Lei Zuhai , Bao Jianming , Wu Jiahui , He Tingting , Hu Fupin , Zheng Jing , Li Honglin , Zhu Weiping , Shao Lei , Dong Xiaojing , Chen Daijie , Qian Xuhong , Yang Youjun 
Published: January 2019

AbstractAntimicrobial resistance is a public health emergency and warrants coordinated global efforts. Challenge is that no alternative molecular platform has been identified for discovery of abundant antimicrobial hit compounds. Xanthene libraries have been screened for bioactive compounds. However, the potentially accessible chemistry space of xanthene dyes is limited by the existing xanthene synthesis. Herein we report a mild one-step synthesis, which permits late-stage introduction of a xanthene moiety onto i.e. natural products, pharmaceuticals, and bioactive compounds and construction of a focused library of rhodamine dyes exhibiting facile functional, topographical and stereochemical diversity. In vitro screening yields 37 analogs with mid-to-high bactericidal activity against WHO priority drug-resistant pathogens. These findings suggest that synthetic dye libraries exhibiting high structural diversity is a feasible chemical space combating antibacterial resistance, to complement the natural sources.
Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms
Authors: Zhang Haijiao , Savage Samantha , Schultz Anna Reister , Bottomly Daniel , White Libbey , Segerdell Erik , Wilmot Beth , McWeeney Shannon K. , Eide Christopher A. , Nechiporuk Tamilla , Carlos Amy , Henson Rachel , Lin Chenwei , Searles Robert , Ho Hoang , Lam Yee Ling , Sweat Richard , Follit Courtney , Jain Vinay , Lind Evan , Borthakur Gautam , Garcia-Manero Guillermo , Ravandi Farhad , Kantarjian Hagop M. , Cortes Jorge , Collins Robert , Buelow Daelynn R. , Baker Sharyn D. , Druker Brian J. , Tyner Jeffrey W. 
Published: January 2019

AbstractFLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.