bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Coupling Between Wave‐Induced Fluid Flow and Elastic Scattering on P‐Wave Dispersion and Attenuation in Rocks With Aligned Fractures
Authors: Guo Junxin , Gurevich Boris
Published: February 2020

Fracture‐background wave‐induced fluid flow (FB‐WIFF) and elastic scattering are considered two important mechanisms for P‐wave dispersion and attenuation in the fractured and porous fluid‐saturated rock. While numerous theoretical models have been proposed to study these two mechanisms, their coupling effects are seldom studied. Hence, in this work, we investigate the coupling between these two mechanisms theoretically based on the Biot equations of dynamic poroelasticity. The P wave is assumed to propagate perpendicular to the fracture plane in the fluid‐saturated porous rock with aligned penny‐shaped fractures. The general solutions are first obtained from the governing equations, then the expressions for the coefficients of the general solutions are derived using the boundary conditions. To illustrate the influencing factors on the coupling between FB‐WIFF and elastic scattering, a numerical example is given. The results show that the coupling strength between FB‐WIFF and elastic scattering are greatly influenced by the ratio of fluid viscosity to background permeability. With the decrease of this ratio, the coupling strength becomes stronger. Furthermore, the coupling effects are also affected by the fracture radius and thickness. However, the fracture density and fluid bulk modulus have negligible influence on the coupling effects. This new model shows good agreement with other theories. Furthermore, comparison of this new model with the linear superposition of FB‐WIFF and elastic scattering indicates the strong nonlinear coupling between these two mechanisms when their characteristic frequencies are close. Finally, the extension of this model and implications of our results for seismic exploration and sonic logging are discussed.
Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma
Authors: Bilich Tatjana , Nelde Annika , Bauer Jens , Walz Simon , Roerden Malte , Salih Helmut R. , Weisel Katja , Besemer Britta , Marcu Ana , Lübke Maren , Schuhmacher Juliane , Neidert Marian C. , Rammensee Hans-Georg , Stevanović Stefan , Walz Juliane S.
Published: February 2020

The B-cell maturation antigen (BCMA) is currently being evaluated as promising tumor-associated surface antigen for T-cell-based immunotherapy approaches, such as CAR T cells and bispecific antibodies, in multiple myeloma (MM). Cytotoxic T cells bearing BCMA-specific T-cell receptors might further allow targeting HLA-presented antigens derived from the intracellular domain of BCMA. By analyzing a mass spectrometry-acquired immunopeptidome dataset of primary MM samples and MM cell lines for BCMA-derived HLA ligands, we identified the naturally presented HLA-B*18-restricted ligand P(BCMA)B*18. Additionally, P(BCMA)B*18 was identified on primary CLL samples, thereby expanding the range for possible applications. P(BCMA)B*18 induced multifunctional BCMA-specific cells de novo from naïve CD8+ T cells of healthy volunteers. These T cells exhibited antigen-specific lysis of autologous peptide-loaded cells. Even in the immunosuppressive context of MM, we detected spontaneous memory T-cell responses against P(BCMA)B*18 in patients. By applying CTLA-4 and PD-1 inhibition in vitro we induced multifunctional P(BCMA)B*18-specific CD8+ T cells in MM patients lacking preexisting BCMA-directed immune responses. Finally, we could show antigen-specific lysis of autologous peptide-loaded target cells and even MM.1S cells naturally presenting P(BCMA)B*18 using patient-derived P(BCMA)B*18-specific T cells. Hence, this BCMA-derived T-cell epitope represents a promising target for T-cell-based immunotherapy and monitoring following immunotherapy in B-cell malignancy patients.
Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis
Authors: Dinh Phuong-Uyen C. , Paudel Dipti , Brochu Hayden , Popowski Kristen D. , Gracieux M. Cyndell , Cores Jhon , Huang Ke , Hensley M. Taylor , Harrell Erin , Vandergriff Adam C. , George Arianna K. , Barrio Raina T. , Hu Shiqi , Allen Tyler A. , Blackburn Kevin , Caranasos Thomas G. , Peng Xinxia , Schnabel Lauren V. , Adler Kenneth B. , Lobo Leonard J. , Goshe Michael B. , Cheng Ke
Published: February 2020

Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.
Iron whiskers on asteroid Itokawa indicate sulfide destruction by space weathering
Authors: Matsumoto Toru , Harries Dennis , Langenhorst Falko , Miyake Akira , Noguchi Takaaki
Published: February 2020

Extraterrestrial iron sulfide is a major mineral reservoir of the cosmochemically and astrobiologically important elements iron and sulfur. Sulfur depletion on asteroids is a long-standing, yet unresolved phenomenon that is of fundamental importance for asteroid evolution and sulfur delivery to the Earth. Understanding the chemistry of such environments requires insight into the behavior of iron sulfides exposed to space. Here we show that troilite (FeS) grains recovered from the regolith of asteroid 25143 Itokawa have lost sulfur during long-term space exposure. We report the wide-spread occurrence of metallic iron whiskers as a decomposition product formed through irradiation of the sulfide by energetic ions of the solar wind. Whisker growth by ion irradiation is a novel and unexpected aspect of space weathering. It implies that sulfur loss occurs rapidly and, furthermore, that ion irradiation plays an important role in the redistribution of sulfur between solids and gas of the interstellar medium.
Quantum scale organic semiconductors for SERS detection of DNA methylation and gene expression
Authors: Ganesh Swarna , Venkatakrishnan Krishnan , Tan Bo
Published: February 2020

Cancer stem cells (CSC) can be identified by modifications in their genomic DNA. Here, we report a concept of precisely shrinking an organic semiconductor surface-enhanced Raman scattering (SERS) probe to quantum size, for investigating the epigenetic profile of CSC. The probe is used for tag-free genomic DNA detection, an approach towards the advancement of single-molecule DNA detection. The sensor detected structural, molecular and gene expression aberrations of genomic DNA in femtomolar concentration simultaneously in a single test. In addition to pointing out the divergences in genomic DNA of cancerous and non-cancerous cells, the quantum scale organic semiconductor was able to trace the expression of two genes which are frequently used as CSC markers. The quantum scale organic semiconductor holds the potential to be a new tool for label-free, ultra-sensitive multiplexed genomic analysis.
Targeting the CK1α/CBX4 axis for metastasis in osteosarcoma
Authors: Wang Xin , Qin Ge , Liang Xiaoting , Wang Wen , Wang Zhuo , Liao Dan , Zhong Li , Zhang Ruhua , Zeng Yi-Xin , Wu Yuanzhong , Kang Tiebang
Published: February 2020

Osteosarcoma, an aggressive malignant cancer, has a high lung metastasis rate and lacks therapeutic target. Here, we reported that chromobox homolog 4 (CBX4) was overexpressed in osteosarcoma cell lines and tissues. CBX4 promoted metastasis by transcriptionally up-regulating Runx2 via the recruitment of GCN5 to the Runx2 promoter. The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. Consistently, CK1α suppressed cell migration and invasion through inhibition of CBX4. There was a reverse correlation between CK1α and CBX4 in osteosarcoma tissues, and CK1α was a valuable marker to predict clinical outcomes in osteosarcoma patients with metastasis. Pyrvinium pamoate (PP) as a selective activator of CK1α could inhibit osteosarcoma metastasis via the CK1α/CBX4 axis. Our findings indicate that targeting the CK1α/CBX4 axis may benefit osteosarcoma patients with metastasis.
Structure of the processive human Pol δ holoenzyme
Authors: Lancey Claudia , Tehseen Muhammad , Raducanu Vlad-Stefan , Rashid Fahad , Merino Nekane , Ragan Timothy J. , Savva Christos G. , Zaher Manal S. , Shirbini Afnan , Blanco Francisco J. , Hamdan Samir M. , De Biasio Alfredo
Published: February 2020

In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol δ–DNA–PCNA complex in the absence and presence of FEN1. Pol δ is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. Alternative holoenzyme conformations reveal important functional interactions that maintain PCNA orientation during synthesis. This work sheds light on the structural basis of Pol δ’s activity in replicating the human genome.
Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency
Authors: Bell Emma , Curry Edward W. , Megchelenbrink Wout , Jouneau Luc , Brochard Vincent , Tomaz Rute A. , Mau King Hang T. , Atlasi Yaser , de Souza Roshni A. , Marks Hendrik , Stunnenberg Hendrik G. , Jouneau Alice , Azuara Véronique
Published: February 2020

Clusters of enhancers, referred as to super-enhancers (SEs), control the expression of cell identity genes. The organisation of these clusters, and how they are remodelled upon developmental transitions remain poorly understood. Here, we report the existence of two types of enhancer units within SEs typified by distinctive CpG methylation dynamics in embryonic stem cells (ESCs). We find that these units are either prone for decommissioning or remain constitutively active in epiblast stem cells (EpiSCs), as further established in the peri-implantation epiblast in vivo. Mechanistically, we show a pivotal role for ESRRB in regulating the activity of ESC-specific enhancer units and propose that the developmentally regulated silencing of ESRRB triggers the selective inactivation of these units within SEs. Our study provides insights into the molecular events that follow the loss of ESRRB binding, and offers a mechanism by which the naive pluripotency transcriptional programme can be partially reset upon embryo implantation.
Selective EMC subunits act as molecular tethers of intracellular organelles exploited during viral entry
Authors: Bagchi Parikshit , Torres Mauricio , Qi Ling , Tsai Billy
Published: February 2020

Although viruses must navigate the complex host endomembrane system to infect cells, the strategies used to achieve this is unclear. During entry, polyomavirus SV40 is sorted from the late endosome (LE) to the endoplasmic reticulum (ER) to cause infection, yet how this is accomplished remains enigmatic. Here we find that EMC4 and EMC7, two ER membrane protein complex (EMC) subunits, support SV40 infection by promoting LE-to-ER targeting of the virus. They do this by engaging LE-associated Rab7, presumably to stabilize contact between the LE and ER. These EMC subunits also bind to the ER-resident fusion machinery component syntaxin18, which is required for SV40-arrival to the ER. Our data suggest that EMC4 and EMC7 act as molecular tethers, inter-connecting two intracellular compartments to enable efficient transport of a virus between these compartments. As LE-to-ER transport of cellular cargos is unclear, our results have broad implications for illuminating inter-organelle cargo transport.
Elucidating the mechanism of heterogeneous Wacker oxidation over Pd-Cu/zeolite Y by transient XAS
Authors: Imbao Jerick , van Bokhoven Jeroen A. , Clark Adam , Nachtegaal Maarten
Published: February 2020

The heterogenization of Wacker catalysts using chloride-free systems can potentially be a good alternative for the commercial homogeneous Wacker oxidation of ethylene, which utilizes excessive aqueous chloride solvents. However, the mechanism of the heterogeneous system has not been clarified, preventing the rational design of better catalysts. Here, we report a transient X-ray absorption spectroscopic (XAS) investigation of the heterogeneous Wacker oxidation over Pd-Cu/zeolite Y coupled with kinetic studies and chemometric analysis. Insight is obtained by operando quickXAS allowing the quantitative determination of rates and thereby revealing a rapid redox reaction involving copper. Our work demonstrates that copper is not only the site of oxygen activation, but is also involved in the formation of undesired carbon dioxide. Without detecting the presence of Cu(0) and Pd(I), our results suggest that two one-electron transfers to two Cu(II) ions to reoxidize Pd(0) is at work in this heterogeneous Wacker catalyst.
Evaluating physicochemical properties of crude oil as indicators of low-salinity–induced wettability alteration in carbonate minerals
Authors: Song Jin , Rezaee Sara , Guo Wenhua , Hernandez Brianna , Puerto Maura , Vargas Francisco M. , Hirasaki George J. , Biswal Sibani L.
Published: February 2020

The injection of low-salinity brine enhances oil recovery by altering the mineral wettability in carbonate reservoirs. However, the reported effectiveness of low-salinity water varies significantly in the literature, and the underlying mechanism of wettability alteration is controversial. In this work, we investigate the relationships between characteristics of crude oils and the oils’ response to low-salinity water in a spontaneous imbibition test, aiming (1) to identify suitable indicators of the effectiveness of low-salinity water and (2) to evaluate possible mechanisms of low-salinity–induced wettability alteration, including rock/oil charge repulsion and microdispersion formation. Seven oils are tested by spontaneous imbibition and fully characterized in terms of their acidity, zeta potential, interfacial tension, microdispersion propensity, water-soluble organics content and saturate-aromatic-resin-asphaltene fractionation. For the first time, the effectiveness of low-salinity water is found to positively correlate with the oil interfacial tension in low-salinity water. Oils with higher interfacial activity are found to respond more positively to low-salinity water. Moreover, cryogenic transmission electron microscopy images suggest that microdispersion is essentially macroemulsion, and its formation is an effective indicator – but not the root cause – of wettability alteration. The repulsive zeta potential for the rock and the oil in low-salinity water is found to be an insufficient condition for wettability alteration in carbonate minerals.
Digital scanning is more accurate than using a periodontal probe to measure the keratinized tissue width
Authors: Lee Jung-Seok , Jeon Yoon-Sun , Strauss Franz-Josef , Jung Hoi-In , Gruber Reinhard
Published: February 2020

This study aimed to compare the accuracy and reliability of digital versus conventional clinical measurements of the width of keratinized tissue. To this end, the keratinized tissue width was measured at 110 tooth sites in 5 pig jaws. The measurements were made at each site using three-dimensional (3D) scanned images and a periodontal probe. The actual keratinized tissue width was subsequently measured on histologic slides prepared from the same sites, and differences between the histologic slides and the digital and clinical measurements were analyzed to determine their accuracy in two measurement rounds. Furthermore, intrarater and interrater reliabilities were evaluated using the intraclass correlation coefficient (ICC). Here we show that the mean differences (and lower/upper limits of agreement) between the histologic and the digital/clinical measurements were 0.10 mm (−1.34/1.54 mm) and 1.11 mm (−0.69/2.92 mm), respectively, in the first round of measurements (p < 0.01), and 0.04 mm (−1.52/1.59 mm) and 1.05 mm (−0.37/2.48 mm) in the second round of measurements (p < 0.01). Moreover, we found that the intrarater reliability was higher for the digital measurements (ICC = 0.97, confidence interval [CI] = 0.96–0.97) than for the clinical measurements (ICC = 0.87, CI = 0.86–0.89; p < 0.01). Taken together, our results demonstrate that digital measurements of the keratinized tissue width using 3D scanned images can replace conventional clinical measurements using a periodontal probe since they are more accurate and reliable.
Α 10-gigawatt attosecond source for non-linear XUV optics and XUV-pump-XUV-probe studies
Authors: Makos I. , Orfanos I. , Nayak A. , Peschel J. , Major B. , Liontos I. , Skantzakis E. , Papadakis N. , Kalpouzos C. , Dumergue M. , Kühn S. , Varju K. , Johnsson P. , L’Huillier A. , Tzallas P. , Charalambidis D.
Published: February 2020

The quantum mechanical motion of electrons and nuclei in systems spatially confined to the molecular dimensions occurs on the sub-femtosecond to the femtosecond timescales respectively. Consequently, the study of ultrafast electronic and, in specific cases, nuclear dynamics requires the availability of light pulses with attosecond (asec) duration and of sufficient intensity to induce two-photon processes, essential for probing the intrinsic system dynamics. The majority of atoms, molecules and solids absorb in the extreme-ultraviolet (XUV) spectral region, in which the synthesis of the required attosecond pulses is feasible. Therefore, the XUV spectral region optimally serves the study of such ultrafast phenomena. Here, we present a detailed review of the first 10-GW class XUV attosecond source based on laser driven high harmonic generation in rare gases. The pulse energy of this source largely exceeds other laser driven attosecond sources and is comparable to the pulse energy of femtosecond Free-Electron-Laser (FEL) XUV sources. The measured pulse duration in the attosecond pulse train is 650 ± 80 asec. The uniqueness of the combined high intensity and short pulse duration of the source is evidenced in non-linear XUV-optics experiments. It further advances the implementation of XUV-pump-XUV-probe experiments and enables the investigation of strong field effects in the XUV spectral region.
Gradient acoustic focusing of sub-micron particles for separation of bacteria from blood lysate
Authors: Van Assche David , Reithuber Elisabeth , Qiu Wei , Laurell Thomas , Henriques-Normark Birgitta , Mellroth Peter , Ohlsson Pelle , Augustsson Per
Published: February 2020

Handling of submicron-sized objects is important in many biochemical and biomedical applications, but few methods today can precisely manipulate this range of particles. We present gradient acoustic focusing that enables flow-through particle separation of submicron particles and cells and we apply it for separation of bacteria from blood lysate to facilitate their detection in whole blood for improved diagnostics. To control suspended objects below the classical 2µm size limit for acoustic focusing, we introduce a co-flowing acoustic impedance gradient to generate a stabilizing acoustic volume force that supresses acoustic streaming. The method is validated theoretically and experimentally using polystyrene particles, Staphylococcus aureus, Streptococcus pneumoniae and Escherichia coli. The applicability of the method is demonstrated by the separation of bacteria from selectively chemically lysed blood. Combined with downstream operations, this new approach opens up for novel methods for sepsis diagnostics.
miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells
Authors: Houri Kei , Mori Tatsufumi , Onodera Yuta , Tsujimoto Takatoshi , Takehara Toshiyuki , Nakao Shinichi , Teramura Takeshi , Fukuda Kanji
Published: February 2020

Elevation of the levels of reactive oxygen species (ROS) is a major tissue-degenerative phenomenon involved in aging and aging-related diseases. The detailed mechanisms underlying aging-related ROS generation remain unclear. Presently, the expression of microRNA (miR)-142-5p was significantly upregulated in bone marrow mesenchymal stem cells (BMMSCs) of aged mice. Overexpression of miR-142 and subsequent observation revealed that miR-142 involved ROS accumulation through the disruption of selective autophagy for peroxisomes (pexophagy). Mechanistically, attenuation of acetyltransferase Ep300 triggered the upregulation of miR-142 in aged BMMSCs, and miR-142 targeted endothelial PAS domain protein 1 (Epas1) was identified as a regulatory protein of pexophagy. These findings support a novel molecular mechanism relating aging-associated ROS generation and organelle degradation in BMMSCs, and suggest a potential therapeutic target for aging-associated disorders that are accompanied by stem cell degeneration.
Social Dilemmas in Nature-Based Tourism Depend on Social Value Orientations
Authors: Honjo Keita , Kubo Takahiro
Published: February 2020

Nature-based tourism (NBT) is vulnerable to a rapid increase in visitors because natural resources are often open access. Market failure caused by over-exploitation of natural resources is an example of social dilemmas in common-pool resource systems. Game theory, which describes people’s decision making under conflicts, has been applied to the analysis of social dilemmas in NBT. However, previous studies use non-cooperative games assuming individualistic players and discuss the emergence of social dilemmas only in a limited situation. Here, we demonstrate, by developing a two-player non-cooperative game of wildlife viewing, that the traditional game-theoretic approach fails to find social dilemmas. By analysing the competition between tour operators (players) with different social value orientations (SVOs), we found that concentration of tours becomes a Pareto-inefficient Nash equilibrium (PINE) when both players are competitive. Whether the wildlife-viewing market is a Prisoner’s dilemma depends on players’ SVOs. Furthermore, we found that fair punishment on competitive players promotes rather than suppresses the emergence of PINE. Our results suggest that the diversity of SVOs is an essential factor in understanding social dilemmas in NBT.
Development of Oxytolerant Salmonella typhimurium Using Radiation Mutation Technology (RMT) for Cancer Therapy
Authors: Gao Shuang , Jung Jong-Hyun , Lin Shun-Mei , Jang A-Yeung , Zhi Yong , Bum Ahn Ki , Ji Hyun-Jung , Hyang Lim Jae , Guo Huichen , Choy Hyon E. , Lim Sangyong , Seo Ho Seong
Published: February 2020

A critical limitation of Salmonella typhimurium (S. typhimurium) as an anti-cancer agent is the loss of their invasive or replicative activities, which results in no or less delivery of anti-cancer agents inside cancer cells in cancer therapy. Here we developed an oxytolerant attenuated Salmonella strain (KST0650) from the parental KST0649 (ΔptsIΔcrr) strain using radiation mutation technology (RMT). The oxytolerant KST0650 strain possessed 20-times higher replication activity in CT26 cancer cells and was less virulent than KST0649. Furthermore, KST0650 migrated effectively into tumor tissues in mice. KST0650 was further equipped with a plasmid harboring a spliced form of the intracellular pro-apoptotic protein sATF6, and the expression of sATF6 was controlled by the radiation-inducible recN promoter. The new strain was named as KST0652, in which sATF6 protein expression was induced in response to radiation in a dose-dependent manner. This strain was effectively delivered inside cancer cells and tumor tissues via the Salmonella type III secretion system (T3SS). In addition, combination treatment with KST0652 and radiation showed a synergistic anti-tumor effect in murine tumor model with complete inhibition of tumor growth and protection against death. In conclusion, we showed that RMT can be used to effectively develop an anti-tumor Salmonella strain for delivering anti-cancer agents inside tumors.
Difference in Clinical Features between Right- and Left-Sided Acute Colonic Diverticulitis
Authors: Lee Kil-yong , Lee Jaeim , Park Youn Young , Kim Younglim , Oh Seong Taek
Published: February 2020

Right colonic diverticulitis (RCD) and left colonic diverticulitis (LCD) may have different clinical features due to the different embryologic origins and anatomical locations of each colon. Therefore, we aimed to compare RCD and LCD in terms of the associated clinical features. We retrospectively collected clinical data from patients who were diagnosed with acute colonic diverticulitis based on computed tomography findings between 2011 and 2017. RCD was defined as colonic diverticulitis extending from the caecum to the transverse colon, and LCD was defined as extending from the splenic flexure to the sigmoid colon. These analyses included 667 patients with RCD and 58 patients with LCD. Relative to the patients with LCD, the patients with RCD were younger (P < 0.001), were more likely to be male (P = 0.033), were taller (P < 0.001), had lower body mass index values (P < 0.001), had less advanced modified Hinchey stages (P < 0.001), and had shorter hospital stays (P < 0.001). Having LCD rather than RCD was a predictor of recurrent colonic diverticulitis (P = 0.003). Relative to LCD, RCD occurs at younger ages, is expressed at less advanced modified Hinchey stages, and is associated with lower risks of recurrence.
A mouse model of pulmonary Mycobacteroides abscessus infection
Authors: Maggioncalda Emily C. , Story-Roller Elizabeth , Mylius Julian , Illei Peter , Basaraba Randall J. , Lamichhane Gyanu
Published: February 2020

There is no preclinical mouse model to investigate pulmonaryMycobacteroides abscessus(formerlyMycobacterium abscessus) infection in an immunocompetent mouse strain, especially in the context of antibiotic testing and regimen development. We developed a mouse model of pulmonaryM. abscessusinfection using the aerosolized route of infection that leads to an increase in bacterial burden post- implantation and develops pathology as a result. In this mouse model, treatment with corticosteroid allows for initial proliferation and sustainedM. abscessuspulmonary infection and permits evaluation of efficacies of antibiotics. Administration of corticosteroids that permitted higher levels of bacterial burden in the lungs were more likely to have pathology. Treatment of mice with antibiotics administered intranasally or subcutaneously significantly reduced lungM. abscessusburden. In addition to the reference strain, independent clinical isolates ofM. abscessusalso readily establish infection and proliferate in the lungs of mice in this model.
Neutron Total Scattering Studies of Group II Titanates (ATiO3, A2+ = Mg, Ca, Sr, Ba)
Authors: Culbertson Charles M. , Flak Alexander T. , Yatskin Michael , Cheong Paul H.-Y. , Cann David P. , Dolgos Michelle R.
Published: February 2020

Neutron total scattering measurements were conducted on MgTiO3, CaTiO3, SrTiO3, and BaTiO3 to simultaneously investigate the local and average structure of these materials. The local structures of MgTiO3, CaTiO3, and SrTiO3 were well modelled using the refined average structural models: trigonal R$$\bar{3}$$3¯, orthorhombic Pbnm, and cubic Pm$$\bar{3}$$3¯m respectively. However the local structure for BaTiO3, at both temperatures where the average structure is orthorhombic Amm2 and tetragonal P4mm, was best described by the rhombohedral R3m model. Only the R3m model was able to account for the observed displacement of titanium in the [111] direction. Furthermore, box-car type refinements were conducted. These refinements show that the coherence length of the rhombohedral distortion is around 10 Å, at larger r-ranges the local distortions become misaligned and average out to Amm2 and P4mm.
Prediction of Molecular Mutations in Diffuse Low-Grade Gliomas using MR Imaging Features
Authors: Shboul Zeina A. , Chen James , M. Iftekharuddin Khan
Published: February 2020

Diffuse low-grade gliomas (LGG) have been reclassified based on molecular mutations, which require invasive tumor tissue sampling. Tissue sampling by biopsy may be limited by sampling error, whereas non-invasive imaging can evaluate the entirety of a tumor. This study presents a non-invasive analysis of low-grade gliomas using imaging features based on the updated classification. We introduce molecular (MGMT methylation, IDH mutation, 1p/19q co-deletion, ATRX mutation, and TERT mutations) prediction methods of low-grade gliomas with imaging. Imaging features are extracted from magnetic resonance imaging data and include texture features, fractal and multi-resolution fractal texture features, and volumetric features. Training models include nested leave-one-out cross-validation to select features, train the model, and estimate model performance. The prediction models of MGMT methylation, IDH mutations, 1p/19q co-deletion, ATRX mutation, and TERT mutations achieve a test performance AUC of 0.83 ± 0.04, 0.84 ± 0.03, 0.80 ± 0.04, 0.70 ± 0.09, and 0.82 ± 0.04, respectively. Furthermore, our analysis shows that the fractal features have a significant effect on the predictive performance of MGMT methylation IDH mutations, 1p/19q co-deletion, and ATRX mutations. The performance of our prediction methods indicates the potential of correlating computed imaging features with LGG molecular mutations types and identifies candidates that may be considered potential predictive biomarkers of LGG molecular classification.
Characterization of a bacteriophage, vB_Eco4M-7, that effectively infects many Escherichia coli O157 strains
Authors: Necel Agnieszka , Bloch Sylwia , Nejman-Faleńczyk Bożena , Grabski Michał , Topka Gracja , Dydecka Aleksandra , Kosznik-Kwaśnicka Katarzyna , Grabowski Łukasz , Jurczak-Kurek Agata , Wołkowicz Tomasz , Węgrzyn Grzegorz , Węgrzyn Alicja
Published: February 2020

The characterization of a recently isolated bacteriophage, vB_Eco4M-7, which effectively infects many, though not all, Escherichia coli O157 strains, is presented. The genome of this phage comprises double-stranded DNA, 68,084 bp in length, with a GC content of 46.2%. It contains 96 putative open reading frames (ORFs). Among them, the putative functions of only 35 ORFs were predicted (36.5%), whereas 61 ORFs (63.5%) were classified as hypothetical proteins. The genome of phage vB_Eco4M-7 does not contain genes coding for integrase, recombinase, repressors or excisionase, which are the main markers of temperate viruses. Therefore, we conclude that phage vB_Eco4M-7 should be considered a lytic virus. This was confirmed by monitoring phage lytic development by a one-step growth experiment. Moreover, the phage forms relatively small uniform plaques (1 mm diameter) with no properties of lysogenization. Electron microscopic analyses indicated that vB_Eco4M-7 belongs to the Myoviridae family. Based on mass spectrometric analyses, including the fragmentation pattern of unique peptides, 33 phage vB_Eco4M-7 proteins were assigned to annotated open reading frames. Importantly, genome analysis suggested that this E. coli phage is free of toxins and other virulence factors. In addition, a similar, previously reported but uncharacterized bacteriophage, ECML-117, was also investigated, and this phage exhibited properties similar to vB_Eco4M-7. Our results indicate that both studied phages are potential candidates for phage therapy and/or food protection against Shiga toxin-producing E. coli, as the majority of these strains belong to the O157 serotype.
Author Correction: Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker
Authors: Murakami Yuki , Imamura Yukio , Saito Kuniaki , Sakai Daisuke , Motoyama Jun
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Characterization of Induced High Yielding Cowpea Mutant Lines Using Physiological, Biochemical and Molecular Markers
Authors: Raina Aamir , Laskar Rafiul Amin , Tantray Younas Rasheed , Khursheed Shahnawaz , Wani Mohd. Rafiq , Khan Samiullah
Published: February 2020

Cowpea, Vigna unguiculata (L.) Walp. is an important grain legume grown in the dry agro-ecologies of the tropics with considerably low yield due to lack of improved varieties, aggravated by prevalent narrow genetic base. Thus, induced mutagenesis was employed using sodium azide and gamma rays to increase genetic variability in cowpea genotypes that resulted in isolation of eleven high yielding mutant lines at the M4 generation from the genetic background of cowpea varieties Gomati VU-89 and Pusa-578. In order to analyze the induced genetic divergence among the mutant lines and parent genotypes, biochemical and molecular characterization was carried out with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), simple sequence repeat (SSR) and CAAT box derived polymorphism (CBDP) markers. Activity of nitrate reductase (NR) and content of chlorophyll, carotenoid, protein and mineral were found to be significantly high in the selected mutant lines compared to their respective parent genotypes. SDS-PAGE profile of seed proteins generated 54 and 28 polymorphic bands and a total polymorphism of 62.06 and 41.17% in Gomati VU-89 and Pusa-578, respectively. SSR primers amplified a total of 16 and 24 polymorphic bands with an average polymorphism of 20.69 and 50.74% in Gomati VU-89 and Pusa-578, respectively. CBDP markers, used for the first time in mutagenized population, generated 175 bands with 77 bands being polymorphic in Gomati VU-89 and 121 bands with 59 bands being polymorphic in Pusa-578. Physiological, biochemical and molecular profiling of the selected promising mutants lines showed that Gomati VU-89-G and Pusa-578-C are genetically most diverged high yielding genotypes with significant increase in protein and micronutrient content, therefore, could be recommended for further research considerations. Thus, the favorable combination of genes induced in the novel cowpea mutants selected through the present study are valuable to correspond farmers requirements for new improved cultivars (direct or hybrids).
Integrated RNA and metabolite profiling of urine liquid biopsies for prostate cancer biomarker discovery
Authors: Lee Bongyong , Mahmud Iqbal , Marchica John , Dereziński Paweł , Qi Feng , Wang Fubo , Joshi Piyush , Valerio Felipe , Rivera Inoel , Patel Vipul , Pavlovich Christian P. , Garrett Timothy. J. , Schroth Gary P. , Sun Yinghao , Perera Ranjan J.
Published: February 2020

Sensitive and specific diagnostic and prognostic biomarkers for prostate cancer (PCa) are urgently needed. Urine samples are a non-invasive means to obtain abundant and readily accessible “liquid biopsies”. Herein we used urine liquid biopsies to identify and characterize a novel group of urine-enriched RNAs and metabolites in patients with PCa and normal individuals with or without benign prostatic disease. Differentially expressed RNAs were identified in urine samples by deep sequencing and metabolites in urine were measured by mass spectrometry. mRNA and metabolite profiles were distinct in patients with benign and malignant disease. Integrated analysis of urinary gene expression and metabolite signatures unveiled an aberrant glutamate metabolism and tricarboxylic acid (TCA) cycle node in prostate cancer-derived cells. Functional validation supported a role for glutamate metabolism and glutamate oxaloacetate transaminase 1 (GOT1)-dependent redox balance in PCa, which could be exploited for novel biomarkers and therapies. In this study, we discovered cancer-specific changes in urinary RNAs and metabolites, paving the way for the development of sensitive and specific urinary PCa diagnostic biomarkers either alone or in combination. Our methodology was based on single void urine samples (i.e., without prostatic massage). The integrated analysis of metabolomic and transcriptomic data from these liquid biopsies revealed a glutamate metabolism and tricarboxylic acid cycle node that was specific to prostate-derived cancer cells and cancer-specific metabolic changes in urine.
Insight into DNA substrate specificity of PARP1-catalysed DNA poly(ADP-ribosyl)ation
Authors: Matta Elie , Kiribayeva Assel , Khassenov Bekbolat , Matkarimov Bakhyt T. , Ishchenko Alexander A.
Published: February 2020

DNA-dependent poly(ADP-ribose) polymerases (PARPs) PARP1, PARP2 and PARP3 act as DNA break sensors signalling DNA damage. Upon detecting DNA damage, these PARPs use nicotine adenine dinucleotide as a substrate to synthesise a monomer or polymer of ADP-ribose (MAR or PAR, respectively) covalently attached to the acceptor residue of target proteins. Recently, it was demonstrated that PARP1–3 proteins can directly ADP-ribosylate DNA breaks by attaching MAR and PAR moieties to terminal phosphates. Nevertheless, little is still known about the mechanisms governing substrate recognition and specificity of PARP1, which accounts for most of cellular PARylation activity. Here, we characterised PARP1-mediated DNA PARylation of DNA duplexes containing various types of breaks at different positions. The 3′-terminal phosphate residue at double-strand DNA break ends served as a major acceptor site for PARP1-catalysed PARylation depending on the orientation and distance between DNA strand breaks in a single DNA molecule. A preference for ADP-ribosylation of DNA molecules containing 3′-terminal phosphate over PARP1 auto-ADP-ribosylation was observed, and a model of DNA modification by PARP1 was proposed. Similar results were obtained with purified recombinant PARP1 and HeLa cell-free extracts. Thus, the biological effects of PARP-mediated ADP-ribosylation may strongly depend on the configuration of complex DNA strand breaks.
Influence of watershed characteristics on streambed hydraulic conductivity across multiple stream orders
Authors: Abimbola Olufemi P. , Mittelstet Aaron R. , Gilmore Troy E. , Korus Jesse T.
Published: February 2020

Streambeds are critical hydrological interfaces: their physical properties regulate the rate, timing, and location of fluxes between aquifers and streams. Streambed vertical hydraulic conductivity (Kv) is a key parameter in watershed models, so understanding its spatial variability and uncertainty is essential to accurately predicting how stresses and environmental signals propagate through the hydrologic system. Most distributed modeling studies use generalized Kv estimates from column experiments or grain-size distribution, but Kv may include a wide range of orders of magnitude for a given particle size group. Thus, precisely predicting Kv spatially has remained conceptual, experimental, and/or poorly constrained. This usually leads to increased uncertainty in modeling results. There is a need to shift focus from scaling up pore-scale column experiments to watershed dimensions by proposing a new kind of approach that can apply to a whole watershed while incorporating spatial variability of complex hydrological processes. Here we present a new approach, Multi-Stemmed Nested Funnel (MSNF), to develop pedo-transfer functions (PTFs) capable of simulating the effects of complex sediment routing on Kv variability across multiple stream orders in Frenchman Creek watershed, USA. We find that using the product of Kv and drainage area as a response variable reduces the fuzziness in selecting the “best” PTF. We propose that the PTF can be used in predicting the ranges of Kv values across multiple stream orders.
Spatio-temporal dynamics of Plasmodium falciparum transmission within a spatial unit on the Colombian Pacific Coast
Authors: Knudson Angélica , González-Casabianca Felipe , Feged-Rivadeneira Alejandro , Pedreros Maria Fernanda , Aponte Samanda , Olaya Adriana , Castillo Carlos F. , Mancilla Elvira , Piamba-Dorado Anderson , Sanchez-Pedraza Ricardo , Salazar-Terreros Myriam Janeth , Lucchi Naomi , Udhayakumar Venkatachalam , Jacob Chris , Pance Alena , Carrasquilla Manuela , Apráez Giovanni , Angel Jairo Andrés , Rayner Julian C. , Corredor Vladimir
Published: February 2020

As malaria control programmes concentrate their efforts towards malaria elimination a better understanding of malaria transmission patterns at fine spatial resolution units becomes necessary. Defining spatial units that consider transmission heterogeneity, human movement and migration will help to set up achievable malaria elimination milestones and guide the creation of efficient operational administrative control units. Using a combination of genetic and epidemiological data we defined a malaria transmission unit as the area contributing 95% of malaria cases diagnosed at the catchment facility located in the town of Guapi in the South Pacific Coast of Colombia. We provide data showing that P. falciparum malaria transmission is heterogeneous in time and space and analysed, using topological data analysis, the spatial connectivity, at the micro epidemiological level, between parasite populations circulating within the unit. To illustrate the necessity to evaluate the efficacy of malaria control measures within the transmission unit in order to increase the efficiency of the malaria control effort, we provide information on the size of the asymptomatic reservoir, the nature of parasite genotypes associated with drug resistance as well as the frequency of the Pfhrp2/3 deletion associated with false negatives when using Rapid Diagnostic Tests.
Transversus Abdominis Plane Block Reduced Early Postoperative Pain after Robot-assisted Prostatectomy: a Randomized Controlled Trial
Authors: Taninishi Hideki , Matsusaki Takashi , Morimatsu Hiroshi
Published: February 2020

Analgesic effect of transversus abdominis plane block (TAP block) in lower major abdominal laparoscopic surgery with about 5 cm of maximum surgical scar has been controversial. We hypothesized that TAP block has benefits, so the analgesic effect of TAP block after robot-assisted laparoscopic prostatectomy (RALP) was evaluated. One hundred patients were enrolled in this prospective, double-blinded, randomized study. Standardized general anesthesia with wound infiltration on camera port and fentanyl dose limit of 3 µg/kg was provided. Ultrasound-guided, single-shot subcostal TAP block with either 0.375% ropivacaine (Ropivacaine group, 48 patients) or normal saline (Control group, 52 patients) was performed by anesthesiologist in charge (34 anesthesiologists) after surgical procedure. Pain score using numerical rating scale (NRS) and postoperative intravenous fentanyl were evaluated for the first 24 postoperative hours. Median values (interquartile range) of NRS scores when the patients were transferred to post-anesthesia care unit (PACU) were 5 (2–7) in Ropivacaine group and 6 (4–8) in Control group at rest (P = 0.03), 5 (2–8) in Ropivacaine group and 7 (5–8) in Control group during movement (P < 0.01). These significant differences disappeared at the time of discharging PACU. Fentanyl doses for the first 24 postoperative hours were 210 µg (120–360) in Ropivacaine group and 200 µg (120–370) in Control group (P = 0.79). These results indicated that subcostal TAP block by anesthesiologists of varied level of training reduced postoperative pain immediate after RALP. TAP block had fundamental analgesic effect, but this benefit was too small to reduce postoperative 24-hour fentanyl consumption.
Lifetime risks, expected years of life lost, and cost-per-life year of esophageal cancer in Taiwan
Authors: Lai Wu-Wei , Lin Chia-Ni , Chang Chao-Chun , Wang Jung-Der
Published: February 2020

Besides lifetime risks, we estimated life expectancy (LE), expected years of life lost (EYLL), lifetime costs, and cost-per-LY (life-year) stratified by different stages of esophageal cancer (EC). From the Taiwan Cancer Registry, we collected 14,420 EC to estimate the incidence rates during 2008–2014. They were followed to 2015 to obtain the survival function, which was extrapolated to lifetime by a semiparametric method. We abstracted the monthly healthcare expenditures from the reimbursement database of National Health Insurance, which were multiplied with the corresponding survival probabilities to quantify lifetime cost and cost-per-LY after adjustments. About 93.7% of patients were male; 90.8% had squamous cell carcinoma. Most patients were diagnosed at advanced stages, with 44.6% and 28.3% at stages III and IV. The lifetime risk of EC in males increased in Taiwan with a cumulative incidence rate (CIR30–84) of 0.0146% (2008~2010) to 0.0165% (2013–2014). The EYLL for stages I-IV were 15.8, 17.5, 20.5, and 22.5, while the average of cost-per-LY for stages I-IV were US$ 6,987, $8,776, $12,153, and $22,426. EC in Taiwan appears to have shifted into younger ages groups and incidence is still increasing. Strategies for prevention, early diagnosis and treatment are warranted to improve the cost-effectiveness and control of this cancer.
A retrospective cohort study of open preperitoneal repair versus open suture repair for the treatment of emergency femoral hernia
Authors: Liu Xiaochun , Ye Lujuan , Zheng Guofu , Ye Bo , Chen Weiqing , Xie Hailiang , Liu Yunqiang , Guo Yi
Published: February 2020

To compare the outcomes of open preperitoneal repair (OPR) with the use of mesh and open suture repair (OSR) without mesh via inguinal approach for the treatment of emergency femoral hernia (FH). The primary outcome was the postoperative complication and the secondary outcomes were the recurrence rate of FH and the postoperative comfort level at the surgical site. 104 patients with emergency FHs were included, of whom 51 patients were treated with OPR, 53 patients were treated with OSR. Between the two groups, no significant difference was found in surgical site infection (SSI) (P = 0.801) or seroma (P = 0.843), while there was significant difference in the improvement of comfort at the surgical site (P = 0.013). The results of the 2-year follow-up demonstrated 1 and 8 cases of recurrence in the OPR and OSR group respectively, which was statistically significant (HR, 8.193 [95% CI, 1.024 to 65.547], P = 0.047). Compared with OSR, OPR with the use of mesh did not increase the risk of SSI and was safe to apply even under the condition of an emergency FH operation with intestine resection; OPR could reduce the recurrence rate of FH and improve the comfort at the surgical site.