bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arkadia/RNF111 is a SUMO-targeted ubiquitin ligase with preference for substrates marked with SUMO1-capped SUMO2/3 chain
Authors: Sriramachandran Annie M. , Meyer-Teschendorf Katrin , Pabst Stefan , Ulrich Helle D. , Gehring Niels H. , Hofmann Kay , Praefcke Gerrit J. K. , Dohmen R. Jürgen 
Published: August 2019

AbstractModification with SUMO regulates many eukaryotic proteins. Down-regulation of sumoylated forms of proteins involves either their desumoylation, and hence recycling of the unmodified form, or their proteolytic targeting by ubiquitin ligases that recognize their SUMO modification (termed STUbL or ULS). STUbL enzymes such as Uls1 and Slx5-Slx8 in budding yeast or RNF4 and Arkadia/RNF111 in humans bear multiple SUMO interaction motifs to recognize substrates carrying poly-SUMO chains. Using yeast as experimental system and isothermal titration calorimetry, we here show that Arkadia specifically selects substrates carrying SUMO1-capped SUMO2/3 hybrid conjugates and targets them for proteasomal degradation. Our data suggest that a SUMO1-specific binding site in Arkadia with sequence similarity to a SUMO1-binding site in DPP9 is required for targeting endogenous hybrid SUMO conjugates and PML nuclear bodies in human cells. We thus characterize Arkadia as a STUbL with a preference for substrate proteins marked with distinct hybrid SUMO chains.
Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese
Authors: Kou Ikuyo , Otomo Nao , Takeda Kazuki , Momozawa Yukihide , Lu Hsing-Fang , Kubo Michiaki , Kamatani Yoichiro , Ogura Yoji , Takahashi Yohei , Nakajima Masahiro , Minami Shohei , Uno Koki , Kawakami Noriaki , Ito Manabu , Yonezawa Ikuho , Watanabe Kei , Kaito Takashi , Yanagida Haruhisa , Taneichi Hiroshi , Harimaya Katsumi , Taniguchi Yuki , Shigematsu Hideki , Iida Takahiro , Demura Satoru , Sugawara Ryo , Fujita Nobuyuki , Yagi Mitsuru , Okada Eijiro , Hosogane Naobumi , Kono Katsuki , Nakamura Masaya , Chiba Kazuhiro , Kotani Toshiaki , Sakuma Tsuyoshi , Akazawa Tsutomu , Suzuki Teppei , Nishida Kotaro , Kakutani Kenichiro , Tsuji Taichi , Sudo Hideki , Iwata Akira , Sato Tatsuya , Inami Satoshi , Matsumoto Morio , Terao Chikashi , Watanabe Kota , Ikegawa Shiro 
Published: August 2019

AbstractAdolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.
Global subsoil organic carbon turnover times dominantly controlled by soil properties rather than climate
Authors: Luo Zhongkui , Wang Guocheng , Wang Enli 
Published: August 2019

AbstractSoil organic carbon (SOC) in the subsoil below 0.3 m accounts for the majority of total SOC and may be as sensitive to climate change as topsoil SOC. Here we map global SOC turnover times (τ) in the subsoil layer at 1 km resolution using observational databases. Global mean τ is estimated to be $$1015_{729}^{1414}$$
101

5

729

1414

yr (mean with 95% confidence interval), and deserts and tundra show the shortest ($$146_{114}^{188}$$
14

6

114

188

yr) and longest ($$3854_{2651}^{5622}$$
385

4

2651

5622

yr) τ respectively. Across the globe, mean τ ranges from 9 (the 5% quantile) to 6332 years (the 95% quantile). Temperature is the most important factor negatively affecting τ, but the overall effect of climate (including temperature and precipitation) is secondary compared with the overall effect of assessed soil properties (e.g., soil texture and pH). The high-resolution mapping of τ and the quantification of its controls provide a benchmark for diagnosing subsoil SOC dynamics under climate change.
Stiffening of graphene oxide films by soft porous sheets
Authors: Mao Lily , Park Hun , Soler-Crespo Rafael A. , Espinosa Horacio D. , Han Tae Hee , Nguyen SonBinh T. , Huang Jiaxing 
Published: August 2019

AbstractGraphene oxide (GO) sheets have been used as a model system to study how the mechanical properties of two-dimensional building blocks scale to their bulk form, such as paper-like, lamellar-structured thin films. Here, we report that the modulus of multilayer GO films can be significantly enhanced if some of the sheets are drastically weakened by introducing in-plane porosity. Nanometer-sized pores are introduced in GO sheets by chemical etching. Membrane-deflection measurements at the single-layer level show that the sheets are drastically weakened as the in-plane porosity increases. However, the mechanical properties of the corresponding multilayer films are much less sensitive to porosity. Surprisingly, the co-assembly of pristine and etched GO sheets yields even stiffer films than those made from pristine sheets alone. This is attributed to the more compliant nature of the soft porous sheets, which act as a binder to improve interlayer packing and load transfer in the multilayer films.
Cancer-associated mutations in DICER1 RNase IIIa and IIIb domains exert similar effects on miRNA biogenesis
Authors: Vedanayagam Jeffrey , Chatila Walid K. , Aksoy Bülent Arman , Majumdar Sonali , Skanderup Anders Jacobsen , Demir Emek , Schultz Nikolaus , Sander Chris , Lai Eric C. 
Published: August 2019

AbstractSomatic mutations in the RNase IIIb domain of DICER1 arise in cancer and disrupt the cleavage of 5' pre-miRNA arms. Here, we characterize an unstudied, recurrent, mutation (S1344L) in the DICER1 RNase IIIa domain in tumors from The Cancer Genome Atlas (TCGA) project and MSK-IMPACT profiling. RNase IIIa/b hotspots are absent from most cancers, but are notably enriched in uterine cancers. Systematic analysis of TCGA small RNA datasets show that DICER1 RNase IIIa-S1344L tumors deplete 5p-miRNAs, analogous to RNase IIIb hotspot samples. Structural and evolutionary coupling analyses reveal constrained proximity of RNase IIIa-S1344 to the RNase IIIb catalytic site, rationalizing why mutation of this site phenocopies known hotspot alterations. Finally, examination of DICER1 hotspot endometrial tumors reveals derepression of specific miRNA target signatures. In summary, comprehensive analyses of DICER1 somatic mutations and small RNA data reveal a mechanistic aspect of pre-miRNA processing that manifests in specific cancer settings.
Interplay of protein corona and immune cells controls blood residency of liposomes
Authors: Giulimondi Francesca , Digiacomo Luca , Pozzi Daniela , Palchetti Sara , Vulpis Elisabetta , Capriotti Anna Laura , Chiozzi Riccardo Zenezini , Laganà Aldo , Amenitsch Heinz , Masuelli Laura , Peruzzi Giovanna , Mahmoudi Morteza , Screpanti Isabella , Zingoni Alessandra , Caracciolo Giulio 
Published: August 2019

AbstractIn vivo liposomes, like other types of nanoparticles, acquire a totally new ‘biological identity’ due to the formation of a biomolecular coating known as the protein corona that depends on and modifies the liposomes’ synthetic identity. The liposome–protein corona is a dynamic interface that regulates the interaction of liposomes with the physiological environment. Here we show that the biological identity of liposomes is clearly linked to their sequestration from peripheral blood mononuclear cells (PBMCs) of healthy donors that ultimately leads to removal from the bloodstream. Pre-coating liposomes with an artificial corona made of human plasma proteins drastically reduces capture by circulating leukocytes in whole blood and may be an effective strategy to enable prolonged circulation in vivo. We conclude with a critical assessment of the key concepts of liposome technology that need to be reviewed for its definitive clinical translation.
Molecular mass growth through ring expansion in polycyclic aromatic hydrocarbons via radical–radical reactions
Authors: Zhao Long , Kaiser Ralf. I. , Lu Wenchao , Xu Bo , Ahmed Musahid , Morozov Alexander N. , Mebel Alexander M. , Howlader A. Hasan , Wnuk Stanislaw F. 
Published: August 2019

AbstractPolycyclic aromatic hydrocarbons (PAHs) represent key molecular building blocks leading to carbonaceous nanoparticles identified in combustion systems and extraterrestrial environments. However, the understanding of their formation and growth in these high temperature environments has remained elusive. We present a mechanism through laboratory experiments and computations revealing how the prototype PAH—naphthalene—can be efficiently formed via a rapid 1-indenyl radical—methyl radical reaction. This versatile route converts five- to six-membered rings and provides a detailed view of high temperature mass growth processes that can eventually lead to graphene-type PAHs and two-dimensional nanostructures providing a radical new view about the transformations of carbon in our universe.
Evidence of conditioned behavior in amoebae
Authors: De la Fuente Ildefonso M. , Bringas Carlos , Malaina Iker , Fedetz María , Carrasco-Pujante Jose , Morales Miguel , Knafo Shira , Martínez Luis , Pérez-Samartín Alberto , López José I. , Pérez-Yarza Gorka , Boyano María Dolores 
Published: August 2019

AbstractAssociative memory is the main type of learning by which complex organisms endowed with evolved nervous systems respond efficiently to certain environmental stimuli. It has been found in different multicellular species, from cephalopods to humans, but never in individual cells. Here we describe a motility pattern consistent with associative conditioned behavior in the microorganismAmoeba proteus. We use a controlled direct-current electric field as the conditioned stimulus, and a specific chemotactic peptide as the unconditioned stimulus. The amoebae are capable of linking two independent past events, generating persistent locomotion movements that can prevail for 44 min on average. We confirm a similar behavior in a related species,Metamoeba leningradensis. Thus, our results indicate that unicellular organisms can modify their behavior during migration by associative conditioning.
Pseudomonas aeruginosa Induced Host Epithelial Cell Mitochondrial Dysfunction
Authors: Maurice Nicholas M. , Bedi Brahmchetna , Yuan Zhihong , Goldberg Joanna B. , Koval Michael , Hart C. Michael , Sadikot Ruxana T. 
Published: August 2019

AbstractThe pathogenicity of P. aeruginosa is dependent on quorum sensing (QS), an inter-bacterial communication system that can also modulate host biology. The innate immune function of the lung mucosal barrier is dependent on proper mitochondrial function. The purpose of this study was to define the mechanism by which bacterial factors modulate host lung epithelial cell mitochondrial function and to investigate novel therapies that ameliorate this effect. 3-oxo-C12-HSL disrupts mitochondrial morphology, attenuates mitochondrial bioenergetics, and induces mitochondrial DNA oxidative injury. Mechanistically, we show that 3-oxo-C12-HSL attenuates expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, antioxidant defense, and cellular respiration, and its downstream effectors in both BEAS-2B and primary lung epithelial cells. Overexpression of PGC-1α attenuates the inhibition in cellular respiration caused by 3-oxo-C12-HSL. Pharmacologic activation of PGC-1α restores barrier integrity in cells treated with 3-oxo-C12-HSL. These data demonstrate that the P. aeruginosa QS molecule, 3-oxo-C12-HSL, alters mitochondrial pathways critical for lung mucosal immunity. Genetic and pharmacologic strategies that activate the PGC-1α pathway enhance host epithelial cell mitochondrial function and improve the epithelial innate response to P. aeruginosa. Therapies that rescue PGC-1α function may provide a complementary approach in the treatment of P. aeruginosa infection.
Donepezil modulates amyloid precursor protein endocytosis and reduction by up-regulation of SNX33 expression in primary cortical neurons
Authors: Takada-Takatori Yuki , Nakagawa Shota , Kimata Riko , Nao Yousuke , Mizukawa Yumiko , Urushidani Tetsuro , Izumi Yasuhiko , Akaike Akinori , Tsuchida Katsuharu , Kume Toshiaki 
Published: August 2019

AbstractDonepezil, a therapeutic drug for Alzheimer’s disease, ameliorates cognitive dysfunction through selective inhibition of acetylcholinesterase. However, recent studies have also reported off-target effects of donepezil that likely contribute to its therapeutic effects. In this study, we investigated the (i) role of donepezil in amyloid precursor protein (APP) processing and (ii) involvement of sorting nexin protein 33 (SNX33), a member of the sorting nexin protein family, in this processing. Results showed that donepezil induces an increase in SNX33 expression in primary cortical neurons. The secretion of sAPPα in culture media increased, whereas the expression of full-length APP in the cell lysate remained unchanged. Exposure of cortical cultures to donepezil led to a decrease in amyloid β (Aβ) protein levels in a concentration- and time-dependent manner. This decrease was not affected by concomitant treatment with acetylcholine receptor antagonists. SNX33 knockdown by target-specific morpholino oligos inhibited the effects of donepezil. Donepezil treatment increased cell membrane surface expression of APP in SNX33 expression-dependent manner. These results suggested that donepezil decreases the level of Aβ by increasing SNX33 expression and APP cleavage by α-secretase in cortical neurons.
A Network of SLC and ABC Transporter and DME Genes Involved in Remote Sensing and Signaling in the Gut-Liver-Kidney Axis
Authors: Rosenthal Sara Brin , Bush Kevin T. , Nigam Sanjay K. 
Published: August 2019

AbstractGenes central to drug absorption, distribution, metabolism and elimination (ADME) also regulate numerous endogenous molecules. The Remote Sensing and Signaling Hypothesis argues that an ADME gene-centered network—including SLC and ABC “drug” transporters, “drug” metabolizing enzymes (DMEs), and regulatory genes—is essential for inter-organ communication via metabolites, signaling molecules, antioxidants, gut microbiome products, uremic solutes, and uremic toxins. By cross-tissue co-expression network analysis, the gut, liver, and kidney (GLK) formed highly connected tissue-specific clusters of SLC transporters, ABC transporters, and DMEs. SLC22, SLC25 and SLC35 families were network hubs, having more inter-organ and intra-organ connections than other families. Analysis of the GLK network revealed key physiological pathways (e.g., involving bile acids and uric acid). A search for additional genes interacting with the network identified HNF4α, HNF1α, and PXR. Knockout gene expression data confirmed ~60–70% of predictions of ADME gene regulation by these transcription factors. Using the GLK network and known ADME genes, we built a tentative gut-liver-kidney “remote sensing and signaling network” consisting of SLC and ABC transporters, as well as DMEs and regulatory proteins. Together with protein-protein interactions to prioritize likely functional connections, this network suggests how multi-specificity combines with oligo-specificity and mono-specificity to regulate homeostasis of numerous endogenous small molecules.
Progressive hyperleukocytosis is a relevant predictive marker for differentiation syndrome, early death, and subsequent relapse in acute promyelocytic leukemia
Authors: Yoon Jae-Ho , Kim Hee-Je , Min Gi June , Park Sung-Soo , Jeon Young-Woo , Lee Sung-Eun , Cho Byung-Sik , Eom Ki-Seong , Kim Yoo-Jin , Lee Seok , Min Chang-Ki , Cho Seok-Goo , Lee Jong Wook 
Published: August 2019

AbstractAcute promyelocytic leukemia (APL) is generally held to have favorable risk, but we have observed a high incidence of early deaths caused by fatal bleeding and differentiation syndrome (DS). We retrospectively analyzed 259 APL patients from 2002 to 2014 who all received all-trans retinoic acid (ATRA) with the support of sufficient transfusions, followed by 4 days of idarubicin. High-risk status was determined as a diagnostic leukocyte count (WBCdx) >10 × 109/L (Sanz criteria). For patients with hyperleukocytosis, we sometimes conducted leukapheresis and also used hydroxyurea and prophylactic dexamethasone. Because we frequently observed patient fatalities from progressive hyperleukocytosis, we also checked the maximum leukocyte count (WBCmax) and stratified patients by their incremental ratios. The 8-week cumulative incidence of early death and DS was 13.5% and 17.8%, respectively. We found that WBCmax correlated better with early death and DS, even in the low-risk group, than WBCdx. Among the patients with WBCdx <10 × 109/L, a WBCmax >43 × 109/L correlated with early death (26.7%) and DS (40.0%). Also, having a WBCdx of 10 to 43 × 109/La that increased to a WBCmax >43 × 109/L correlated with increased early death (33.3%). The multivariate analysis revealed that a WBCmax >43 × 109/L correlated significantly with both early death and DS.
Molecular profiling and antimicrobial resistance of Shiga toxin-producing Escherichia coli O26, O45, O103, O121, O145 and O157 isolates from cattle on cow-calf operations in South Africa
Authors: Karama Musafiri , Mainga Alfred O. , Cenci-Goga Beniamino T. , Malahlela Mogaugedi , El-Ashram Saeed , Kalake Alan 
Published: August 2019

AbstractIn this study, 140 cattle STEC isolates belonging to serogroups O157, O26, O145, O121, O103 and O45 were characterized for 38 virulence-associated genes, antimicrobial resistance profiles and genotyped by PFGE. The majority of isolates carried both stx1 and stx2 concurrently, stx2c, and stx2d; plasmid-encoded genes ehxA, espP, subA and saa but lacked katP and etpD and eaeA. Possession of eaeA was significantly associated with the presence of nle genes, katP, etpD, ureC and terC. However, saa and subA, stx1c and stx1d were only detected in eaeA negative isolates. A complete OI-122 and most non-LEE effector genes were detected in only two eaeA positive serotypes, including STEC O157:H7 and O103:H2. The eaeA gene was detected in STEC serotypes that are commonly implicated in severe humans disease and outbreaks including STEC O157:H7, STEC O145:H28 and O103:H2. PFGE revealed that the isolates were highly diverse with very low rates of antimicrobial resistance. In conclusion, only a small number of cattle STEC serotypes that possessed eaeA, had the highest number of virulence-associated genes, indicative of their high virulence. Further characterization of STEC O157:H7, STEC O145:H28 and O103:H2 using whole genome sequencing will be needed to fully understand their virulence potential for humans.
Development of anchialine cave habitats and karst subterranean estuaries since the last ice age
Authors: van Hengstum Peter J. , Cresswell Jacque N. , Milne Glenn A. , Iliffe Thomas M. 
Published: August 2019

AbstractExtinction models generally predict that coastal and neritic fauna benefit during sea-level rise (transgression), whereas sea-level retreat (regression) diminishes their suitable habitat area and promotes evolutionary bottlenecks. Sea-level change also impacts terrestrial island biogeography, but it remains a challenge to evidence how sea-level rise impacts aquatic island biogeography, especially in the subterranean realm. Karst subterranean estuaries (KSEs) occur globally on carbonate islands and platforms, and they are populated by globally-dispersed, ancient ecosystems (termed anchialine). Anchialine fauna currently exhibit a disjunct biogeography that cannot be completely explained by plate tectonic-imposed vicariance. Here we provide evidence that anchialine ecosystems can experience evolutionary bottlenecks caused by habitat reduction during transgression events. Marine-adapted anchialine fauna benefit from habitat expansion during transgressions, but fresh- and brackish-adapted fauna must emigrate, evolve to accommodate local habitat changes, or are regionally eliminated. Phanerozoic transgressions relative to long-term changes in subsidence and relief of regional lithology must be considered for explaining biogeography, evolution, local extirpation or complete extinction of anchialine fauna. Despite the omission of this entire category of environments and animals in climate change risk assessments, the results indicate that anchialine fauna on low-lying islands and platforms that depend upon meteoric groundwater are vulnerable to habitat changes caused by 21st century sea-level rise.
Wavelength-adaptable effective q-plates with passively tunable retardance
Authors: B Radhakrishna , Kadiri Gururaj , Raghavan G 
Published: August 2019

AbstractWave retarders having spatially varying optical axes orientations, called q-plates are extremely efficient devices for converting spin to orbital angular momentum of light and for the generation of optical vortices. Most often, these plates are designed for a specific wavelength and have a homogeneous constant retardance. The present work provides a polarimetric approach for overcoming both these limitations. We theoretically propose and experimentally demonstrate q-plates with tunable retardance, employing a combination of only standard q-plates and waveplates. A clear prescription is provided for realizing wavelength indepedent q-plates for a desired retardance, with a potential for ultrafast switching. Apart from the potential commercial value of the proposed devices, our results may find applications in quantum communication protocols, astronomical coronography, angular momentum sorting and in schemes that leverage optical vortices and spin to orbital angular momentum conversion.
AMPK activation, eEF2 inactivation, and reduced protein synthesis in the cerebral cortex of hibernating chipmunks
Authors: Yamada Shintaro , Kamata Taito , Nawa Hiroyuki , Sekijima Tsuneo , Takei Nobuyuki 
Published: August 2019

AbstractDuring hibernation, mammalian cells are exposed to severe environmental stressors such as low temperature, lowered O2 supply, and glucose deficiency. The cellular metabolic rate is markedly reduced for adapting to these conditions. AMP-activated protein kinase (AMPK) senses the cellular energy status and regulates metabolism. Therefore, we examined AMPK signaling in several brain regions and peripheral tissues in hibernating chipmunk. Eukaryotic elongation factor 2 (eEF2) is a downstream target of AMPK. Phosphorylation of eEF2, indicating its inactivation, is enhanced in the cerebral cortex of hibernating chipmunks. The study indicated that the sequential regulation of AMPK-mammalian target of rapamycin complex 1-eEF2 signaling was altered and protein synthesis ability was reduced in the cerebral cortex of hibernating chipmunks.