bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capillary Trapping of CO2 in Sandstone Using Low Field NMR Relaxometry
Authors: Connolly Paul R. J. , Vogt Sarah J. , Mahmoud Mohamed , Ng Christopher N. Y. , May Eric F. , Johns Michael L. 
Published: November 2019

AbstractInjecting carbon dioxide into geological formations for long‐term storage is considered integral to reducing greenhouse gas emissions. Residual trapping of CO2 is a primary storage mechanism, whereby CO2 ganglia are trapped in the pore space by capillary forces. Experimental knowledge of residual trapping processes in rocks is critical to the development of safe storage strategies. Here we present a quantitative low field 1H nuclear magnetic resonance (NMR) core flooding study of CO2 residual trapping in three different sandstones. It was found that transverse relaxation (T2) measurements were sensitive to the dissolution of paramagnetic ions from rock matrix minerals after exposure to carbonic acid; this response was observed on time scales relevant to core flooding experiments (i.e., minutes to hours). Subsequently, a brine aging protocol was designed and implemented to minimize this chemical effect, and hence, by applying the well‐known T2‐pore size relationship, changes in T2 time distributions during core flooding could be related to displacement of brine from pores of different sizes. Comparison of T2 distributions for partially CO2/brine‐saturated cores to previously published data for N2/H2O systems shows an increased displacement of brine from small pores by CO2. Furthermore, results from cyclical brine/CO2 injections showed an increase in the total volume of residually trapped CO2 and an increase in trapping efficiency; compared to the results observed for N2/H2O, however, the improvement in trapping efficiency with cyclic injection was less pronounced. Potential causes for the observed differences are discussed in the context of effective N2 and CO2 wetting.
Maternal Type-I interferon signaling adversely affects the microglia and the behavior of the offspring accompanied by increased sensitivity to stress
Authors: Ben-Yehuda Hila , Matcovitch-Natan Orit , Kertser Alexander , Spinrad Amit , Prinz Marco , Amit Ido , Schwartz Michal 
Published: November 2019

AbstractViral infection during pregnancy is often associated with neuropsychiatric conditions. In mice, exposure of pregnant dams to the viral mimetic poly(I:C), serves as a model that simulates such pathology in the offspring, through a process known as Maternal Immune Activation (MIA). To investigate the mechanism of such effect, we hypothesized that maternal upregulation of Type-I interferon (IFN-I), as part of the dam’s antiviral response, might contribute to the damage imposed on the offspring. Using mRNA sequencing and flow cytometry analyses we found that poly(I:C) treatment during pregnancy caused reduced expression of genes related to proliferation and cell cycle in the offspring’s microglia relative to controls. This was found to be associated with an IFN-I signature in the embryonic yolk sac, the origin of microglia in development. Neutralizing IFN-I signaling in dams attenuated the effect of MIA on the newborn’s microglia, while systemic maternal administration of IFNβ was sufficient to mimic the effect of poly(I:C), and led to increased vulnerability of offspring’s microglia to subsequent stress. Furthermore, maternal elevation of IFNβ resulted in behavioral manifestations reminiscent of neuropsychiatric disorders. In addition, by adopting a “two-hit” experimental paradigm, we show a higher sensitivity of the offspring to postnatal stress subsequent to the maternal IFNβ elevation, demonstrated by behavioral irregularities. Our results suggest that maternal upregulation of IFN-I, in response to MIA, interferes with the offspring’s programmed microglial developmental cascade, increases their susceptibility to postnatal stress, and leads to behavioral abnormalities.
Hippocampal Lnx1–NMDAR multiprotein complex mediates initial social memory
Authors: Liu Xian-Dong , Ai Peng-Hui , Zhu Xiao-Na , Pan Yuan-Bo , Halford Michael M. , Henkemeyer Mark , Feng Dong-Fu , Xu Tian-Le , Sun Suya , Xu Nan-Jie 
Published: November 2019

AbstractSocial interaction and communication are evolutionary conserved behaviours that are developed in mammals to establish partner cognition. Deficit in sociability has been represented in human patients and animal models of neurodevelopmental disorders, which are connected with genetic variants of synaptic glutamate receptors and associated PDZ-binding proteins. However, it remains elusive how these key proteins are specialized in the cellular level for the initial social behaviour during postnatal developmental stage. Here we identify a hippocampal CA3 specifically expressed PDZ scaffold protein Lnx1 required for initial social behaviour. Through gene targeting we find that Lnx1 deficiency led to a hippocampal subregional disorder in neuronal activity and social memory impairments for partner discrimination observed in juvenile mice which also show cognitive defects in adult stage. We further demonstrate that Lnx1 deletion causes NMDA receptor (NMDAR) hypofunction and this is attributable to decreased GluN2B expression in PSD compartment and disruption of the Lnx1–NMDAR–EphB2 complex. Specific restoration of Lnx1 or EphB2 protein in the CA3 area of Lnx1−/− mice rescues the defective synaptic function and social memory. These findings thus reveal crucial roles of postsynaptic NMDAR multiprotein complex that regulates the formation of initial social memory during the adolescent period.
PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone
Authors: Liang Jinqian , Zhang Xiang-yang , Zhen Yun-Fang , Chen Chong , Tan Haining , Hu Jianhua , Tan Ming-sheng 
Published: November 2019

AbstractActivation of nuclear-factor-E2-related factor 2 (Nrf2) cascade can alleviate dexamethasone (DEX)-induced oxidative injury and death of human osteoblasts. A recent study has shown that phosphoglycerate kinase 1 (PGK1) inhibition/depletion will lead to Kelch-like ECH-associated protein 1 (Keap1) methylglyoxal modification, thereby activating Nrf2 signaling cascade. Here, in OB-6 osteoblastic cells and primary human osteoblasts, PGK1 silencing, by targeted shRNA, induced Nrf2 signaling cascade activation, causing Nrf2 protein stabilization and nuclear translocation, as well as increased expression of ARE-dependent genes (HO1, NQO1, and GCLC). Functional studies demonstrated that PGK1 shRNA largely attenuated DEX-induced oxidative injury and following death of OB-6 cells and primary osteoblasts. Furthermore, PGK1 knockout, by the CRISPR/Cas9 method, similarly induced Nrf2 signaling activation and protected osteoblasts from DEX. Importantly, PGK1 depletion-induced osteoblast cytoprotection against DEX was almost abolished by Nrf2 shRNA. In addition, Keap1 shRNA mimicked and nullified PGK1 shRNA-induced anti-DEX osteoblast cytoprotection. At last we show that PGK1 expression is downregulated in human necrotic femoral head tissues of DEX-taking patients, correlating with HO1 depletion. Collectively, these results show that PGK1 depletion protects human osteoblasts from DEX via activation of Keap1-Nrf2 signaling cascade.
High-efficiency and integrable DNA arithmetic and logic system based on strand displacement synthesis
Authors: Su Haomiao , Xu Jinglei , Wang Qi , Wang Fuan , Zhou Xiang 
Published: November 2019

AbstractPowerful information processing and ubiquitous computing are crucial for all machines and living organisms. The Watson-Crick base-pairing principle endows DNA with excellent recognition and assembly abilities, which facilitates the design of DNA computers for achieving intelligent systems. However, current DNA computational systems are always constrained by poor integration efficiency, complicated device structures or limited computational functions. Here, we show a DNA arithmetic logic unit (ALU) consisting of elemental DNA logic gates using polymerase-mediated strand displacement. The use of an enzyme resulted in highly efficient logic gates suitable for multiple and cascaded computation. Based on our basic single-rail DNA configuration, additional combined logic gates (e.g., a full adder and a 4:1 multiplexer) have been constructed. Finally, we integrate the gates and assemble the crucial ALU. Our strategy provides a facile strategy for assembling a large-scale complex DNA computer system, highlighting the great potential for programming the molecular behaviors of complicated biosystems.
Structural basis for DNA unwinding at forked dsDNA by two coordinating Pif1 helicases
Authors: Su Nannan , Byrd Alicia K. , Bharath Sakshibeedu R. , Yang Olivia , Jia Yu , Tang Xuhua , Ha Taekjip , Raney Kevin D. , Song Haiwei 
Published: November 2019

AbstractPif1 plays multiple roles in maintaining genome stability and preferentially unwinds forked dsDNA, but the mechanism by which Pif1 unwinds forked dsDNA remains elusive. Here we report the structure of Bacteroides sp Pif1 (BaPif1) in complex with a symmetrical double forked dsDNA. Two interacting BaPif1 molecules are bound to each fork of the partially unwound dsDNA, and interact with the 5′ arm and 3′ ss/dsDNA respectively. Each of the two BaPif1 molecules is an active helicase and their interaction may regulate their helicase activities. The binding of BaPif1 to the 5′ arm causes a sharp bend in the 5′ ss/dsDNA junction, consequently breaking the first base-pair. BaPif1 bound to the 3′ ss/dsDNA junction impacts duplex unwinding by stabilizing the unpaired first base-pair and engaging the second base-pair poised for breaking. Our results provide an unprecedented insight into how two BaPif1 coordinate with each other to unwind the forked dsDNA.
Estimation of the apnea-hypopnea index in a heterogeneous sleep-disordered population using optimised cardiovascular features
Authors: Papini Gabriele B. , Fonseca Pedro , van Gilst Merel M. , van Dijk Johannes P. , Pevernagie Dirk A. A. , Bergmans Jan W. M. , Vullings Rik , Overeem Sebastiaan 
Published: November 2019

AbstractObstructive sleep apnea (OSA) is a highly prevalent sleep disorder, which results in daytime symptoms, a reduced quality of life as well as long-term negative health consequences. OSA diagnosis and severity rating is typically based on the apnea-hypopnea index (AHI) retrieved from overnight poly(somno)graphy. However, polysomnography is costly, obtrusive and not suitable for long-term recordings. Here, we present a method for unobtrusive estimation of the AHI using ECG-based features to detect OSA-related events. Moreover, adding ECG-based sleep/wake scoring yields a fully automatic method for AHI-estimation. Importantly, our algorithm was developed and validated on a combination of clinical datasets, including datasets selectively including OSA-pathology but also a heterogeneous, “real-world” clinical sleep disordered population (262 participants in the validation set). The algorithm provides a good representation of the current gold standard AHI (0.72 correlation, estimation error of 0.56 ± 14.74 events/h), and can also be employed as a screening tool for a large range of OSA severities (ROC AUC ≥ 0.86, Cohen’s kappa ≥ 0.53 and precision ≥70%). The method compares favourably to other OSA monitoring strategies, showing the feasibility of cardiovascular-based surrogates for sleep monitoring to evolve into clinically usable tools.
Novel redox-active enzymes for ligninolytic applications revealed from multiomics analyses of Peniophora sp. CBMAI 1063, a laccase hyper-producer strain
Authors: Brenelli Lívia B. , Persinoti Gabriela F. , Cairo João Paulo L. Franco , Liberato Marcelo V. , Gonçalves Thiago Augusto , Otero Igor V. R. , Mainardi Pedro H. , Felby Claus , Sette Lara D. , Squina Fabio M. 
Published: November 2019

AbstractThe repertoire of redox-active enzymes produced by the marine fungusPeniophorasp. CBMAI 1063, a laccase hyper-producer strain, was characterized by omics analyses. The genome revealed 309 Carbohydrate-Active Enzymes (CAZymes) genes, including 48 predicted genes related to the modification and degradation of lignin, whith 303 being transcribed under cultivation in optimized saline conditions for laccase production. The secretome confirmed that the fungus can produce a versatile ligninolytic enzyme cocktail. It secretes 56 CAZymes, including 11 oxidative enzymes classified as members of auxiliary activity families (AAs), comprising two laccases, Pnh_Lac1 and Pnh_Lac2, the first is the major secretory protein of the fungi. The Pnh_Lac1-mediator system was able to promote the depolymerization of lignin fragments and polymeric lignin removal from pretreated sugarcane bagasse, confirming viability of this fungus enzymatic system for lignocellulose-based bioproducts applications.
Multimodal Cleavable Reporters for Quantifying Carboxy and Amino Groups on Organic and Inorganic Nanoparticles
Authors: Nirmalananthan-Budau Nithiya , Rühle Bastian , Geißler Daniel , Moser Marko , Kläber Christopher , Schäfer Andreas , Resch-Genger Ute 
Published: November 2019

AbstractOrganic and inorganic nanoparticles (NPs) are increasingly used as drug carriers, fluorescent sensors, and multimodal labels in the life and material sciences. These applications require knowledge of the chemical nature, total number of surface groups, and the number of groups accessible for subsequent coupling of e.g., antifouling ligands, targeting bioligands, or sensor molecules. To establish the concept of catch-and-release assays, cleavable probes were rationally designed from a quantitatively cleavable disulfide moiety and the optically detectable reporter 2-thiopyridone (2-TP). For quantifying surface groups on nanomaterials, first, a set of monodisperse carboxy-and amino-functionalized, 100 nm-sized polymer and silica NPs with different surface group densities was synthesized. Subsequently, the accessible functional groups (FGs) were quantified via optical spectroscopy of the cleaved off reporter after its release in solution. Method validation was done with inductively coupled plasma optical emission spectroscopy (ICP-OES) utilizing the sulfur atom of the cleavable probe. This comparison underlined the reliability and versatility of our probes, which can be used for surface group quantification on all types of transparent, scattering, absorbing and/or fluorescent particles. The correlation between the total and accessible number of FGs quantified by conductometric titration, qNMR, and with our cleavable probes, together with the comparison to results of conjugation studies with differently sized biomolecules reveal the potential of catch-and-release reporters for surface analysis. Our findings also underline the importance of quantifying particularly the accessible amount of FGs for many applications of NPs in the life sciences.
Mass production of a S-layer protein of Bacillus thuringiensis and its toxicity to the cattle tick Rhipicephalus microplus
Authors: Lormendez Caleb C. , Fernandez-Ruvalcaba Manuel , Adames-Mancebo Markis , Hernandez-Velazquez Victor Manuel , Zuñiga-Navarrete Fernando , Flores-Ramirez Gabriela , Lina-Garcia Laura , Peña-Chora Guadalupe 
Published: November 2019

AbstractThe most commonly used biopesticides to control agricultural, forest and insect vectors of human diseases are derived from the bacterium Bacillus thuringiensis, which begins to produce Cry and Cyt insecticidal proteins during the onset of the sporulation phase. Some B. thuringiensis strains also produce S-layer proteins that are toxic to certain pests. S-layer proteins are the most abundant proteins in bacteria and archaea. This proteins’ key trait to design high performace processes for mass production is their continuous expression during the vegetative phase, unlike Cry and Cyt, which are restricted to the sporulation phase. In this work, a S-layer protein expressed by the GP543 strain of B. thuringiensis that is toxic to the cattle tick Rhipicephalus microplus was mass produced using the batch culture fermentation technique. In addition, the spore-protein complex showed a mortality rate of 75% with a dose of 300 µg·mL−1 on adult females of R. microplus after fourteen days. The lethal concentration 50 was 69.7 µg·mL−1. The treatment also caused a decrease of 13% in the weight of the mass of oviposited eggs with 200 µg·mL−1 of the spore-protein complex and inhibition of the hatching of eggs from 80 to 92%. Therefore, this could be a good option for controlling this parasite. The advantages of S-layer protein synthesis are focused on the production of a new generation of proteins in pest control. This is the first report on the mass production of an S-layer protein that is responsible for toxicity.
Tumor core biopsies adequately represent immune microenvironment of high-grade serous carcinoma
Authors: Lara Olivia D. , Krishnan Santhoshi , Wang Zhihui , Corvigno Sara , Zhong YanPing , Lyons Yasmin , Dood Robert , Hu Wei , Qi Lisha , Liu Jinsong , Coleman Robert L. , Westin Shannon N. , Fleming Nicole D. , Cristini Vittorio , Rao Arvind , Burks Jared , Sood Anil K. 
Published: November 2019

AbstractThe prognostic and therapeutic value of the tumor microenvironment (TME) in various cancer types is of major interest. Characterization of the TME often relies on a small representative tissue sample. However, the adequacy of such a sample for assessing components of the TME is not yet known. Here, we used immunohistochemical (IHC) staining and 7-color multiplex staining to evaluate CD8 (cluster of differentiation 8), CD68, PD-L1 (programmed death-ligand 1), CD34, FAP (fibroblast activation protein), and cytokeratin in 220 tissue cores from 26 high-grade serous ovarian cancer samples. Comparisons were drawn between a larger tumor specimen and smaller core biopsies based on number and location (central tumor vs. peripheral tumor) of biopsies. Our analysis found that the correlation between marker-specific cell subsets in larger tumor versus smaller core was stronger with two core biopsies and was not further strengthened with additional biopsies. Moreover, this correlation was consistently strong regardless of whether the biopsy was taken at the center or at the periphery of the original tumor sample. These findings could have a substantial impact on longitudinal assessment for detection of biomarkers in clinical trials.
Identification of Sero-Diagnostic Antigens for the Early Diagnosis of Johne’s Disease using MAP Protein Microarrays
Authors: Li Lingling , Bannantine John P. , Campo Joseph J. , Randall Arlo , Grohn Yrjo T. , Schilling Megan A. , Katani Robab , Radzio-Basu Jessica , Easterling Laurel , Kapur Vivek 
Published: November 2019

AbstractConsiderable effort has been directed toward controlling Johne’s disease (JD), a chronic granulomatous intestinal inflammatory disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) in cattle and other ruminants. However, progress in controlling the spread of MAP infection has been impeded by the lack of reliable diagnostic tests that can identify animals early in the infection process and help break the transmission chain. To identify reliable antigens for early diagnosis of MAP infection, we constructed a MAP protein array with 868 purified recombinant MAP proteins, and screened a total of 180 well-characterized serum samples from cows assigned to 4 groups based on previous serological and fecal test results: negative low exposure (NL, n = 30); negative high exposure (NH, n = 30); fecal-positive, ELISA-negative (F + E−, n = 60); and both fecal- and ELISA-positive (F + E+, n = 60). The analyses identified a total of 49 candidate antigens in the NH, F + E−, and F + E+ with reactivity compared with the NL group (p < 0.01), a majority of which have not been previously identified. While some of the antigens were identified as reactive in only one of the groups, others showed reactivity in multiple groups, including NH (n = 28), F + E− (n = 26), and F + E+ (n = 17) groups. Using combinations of top reactive antigens in each group, the results reveal sensitivities of 60.0%, 73.3%, and 81.7% in the NH, F + E−, and F + E+, respectively at 90% specificity, suggesting that early detection of infection in animals may be possible and enable better opportunities to reduce within herd transmission that may be otherwise missed by traditional serological assays that are biased towards more heavily infected animals. Together, the results suggest that several of the novel candidate antigens identified in this study, particularly those that were reactive in the NH and F + E− groups, have potential utility for the early sero-diagnosis of MAP infection.
Predictive and prognostic significance of telomerase levels/telomere length in tissues and peripheral blood in head and neck squamous cell carcinoma
Authors: Boscolo-Rizzo Paolo , Rampazzo Enrica , Polesel Jerry , Giunco Silvia , Menegaldo Anna , Mantovani Monica , Stellin Marco , Bandolin Luigia , Spinato Giacomo , Del Mistro Annarosa , Borsetto Daniele , Fussey Jonathan , Tirelli Giancarlo , Da Mosto Maria Cristina , De Rossi Anita 
Published: November 2019

AbstractA growing body of evidence indicates that the expression of TERT, the catalytic subunit of telomerase, is a biological marker of progression in several cancers. We investigated the predictive and prognostic role of TERT levels and telomere length in tissues and peripheral blood in patients with head and neck squamous cell carcinoma (HNSCC). High TERT levels in cancer tissues were independently associated with worse response to therapy (odds ratio [OR]:6.26), regional failure (hazard ratio [HR]:5.75), progression (HR:2.12), and death (HR:3.53). Longer telomeres in the mucosa surrounding the tumor (SM) were independently associated with a lower risk of mucosal failure (HR:0.39). While telomere length in peripheral blood mononuclear cells (PBMC) significantly decreased with age, no correlation was found between age and telomere length in SM. No associations were found between TERT levels in plasma and telomere length in PBMC and the prognostic variables. High levels of TERT transcripts in cancer cells represent a reliable prognostic marker for identifying HNSCC patients with risk of progression. The altered relationship of telomere length to age in SM compared with PBMC suggests that in a subset of cases the phenotypically normal SM constitutes an acquired telomere-shortened epithelial field prone to genetic instability.
Spa-RQ: an Image Analysis Tool to Visualise and Quantify Spatial Phenotypes Applied to Non-Small Cell Lung Cancer
Authors: Bao Jie , Walliander Margarita , Kovács Ferenc , Nagaraj Ashwini S. , Hemmes Annabrita , Sarhadi Virinder Kaur , Knuutila Sakari , Lundin Johan , Horvath Peter , Verschuren Emmy W. 
Published: November 2019

AbstractTo facilitate analysis of spatial tissue phenotypes, we created an open-source tool package named ‘Spa-RQ’ for ‘Spatial tissue analysis: image Registration & Quantification’. Spa-RQ contains software for image registration (Spa-R) and quantitative analysis of DAB staining overlap (Spa-Q). It provides an easy-to-implement workflow for serial sectioning and staining as an alternative to multiplexed techniques. To demonstrate Spa-RQ’s applicability, we analysed the spatial aspects of oncogenic KRAS-related signalling activities in non-small cell lung cancer (NSCLC). Using Spa-R in conjunction with ImageJ/Fiji, we first performed annotation-guided tumour-by-tumour phenotyping using multiple signalling markers. This analysis showed histopathology-selective activation of PI3K/AKT and MAPK signalling in Kras mutant murine tumours, as well as high p38MAPK stress signalling in p53 null murine NSCLC. Subsequently, Spa-RQ was applied to measure the co-activation of MAPK, AKT, and their mutual effector mTOR pathway in individual tumours. Both murine and clinical NSCLC samples could be stratified into ‘MAPK/mTOR’, ‘AKT/mTOR’, and ‘Null’ signature subclasses, suggesting mutually exclusive MAPK and AKT signalling activities. Spa-RQ thus provides a robust and easy to use tool that can be employed to identify spatially-distributed tissue phenotypes.