bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topological scoring of protein interaction networks
Authors: Sardiu Mihaela E. , Gilmore Joshua M. , Groppe Brad D. , Dutta Arnob , Florens Laurence , Washburn Michael P. 
Published: March 2019

AbstractIt remains a significant challenge to define individual protein associations within networks where an individual protein can directly interact with other proteins and/or be part of large complexes, which contain functional modules. Here we demonstrate the topological scoring (TopS) algorithm for the analysis of quantitative proteomic datasets from affinity purifications. Data is analyzed in a parallel fashion where a prey protein is scored in an individual affinity purification by aggregating information from the entire dataset. Topological scores span a broad range of values indicating the enrichment of an individual protein in every bait protein purification. TopS is applied to interaction networks derived from human DNA repair proteins and yeast chromatin remodeling complexes. TopS highlights potential direct protein interactions and modules within complexes. TopS is a rapid method for the efficient and informative computational analysis of datasets, is complementary to existing analysis pipelines, and provides important insights into protein interaction networks.
A novel range-verification method using ionoacoustic wave generated from spherical gold markers for particle-beam therapy: a simulation study
Authors: Takayanagi Taisuke , Uesaka Tomoki , Kitaoka Masanori , Unlu Mehmet Burcin , Umegaki Kikuo , Shirato Hiroki , Xing Lei , Matsuura Taeko 
Published: March 2019

AbstractThis study proposes a novel alternative range-verification method for proton beam with acoustic waves generated from spherical metal markers. When proton beam is incident on metal markers, most of the resulting pressure waves are confined in the markers because of the large difference in acoustic impedance between the metal and tissue. However, acoustic waves with frequency equal to marker’s resonant frequency escape this confinement; the marker briefly acts as an acoustic transmitter. Herein, this phenomenon is exploited to measure the range of the proton beam. We test the proposed strategy in 3-D simulations, combining the dose calculations with modelling of acoustic-wave propagation. A spherical gold marker of 2.0 mm diameter was placed in water with a 60 MeV proton beam incident on it. We investigated the dependence of pressure waves on the width of beam pulse and marker position. At short beam pulse, specific high-frequency acoustic waves of 1.62 MHz originating from the marker were observed in wave simulations, whose amplitude correlated with the distance between the marker and Bragg peak. Results indicate that the Bragg peak position can be estimated by measuring the acoustic wave amplitudes from the marker, using a single detector properly designed for the resonance frequency.
HIV infection and latency induce a unique metabolic signature in human macrophages
Authors: Castellano Paul , Prevedel Lisa , Valdebenito Silvana , Eugenin Eliseo A. 
Published: March 2019

AbstractCurrently, a major barrier to curing HIV infection is the generation of tissue-associated, non-replicating, long-lasting viral reservoirs that are refractory to therapy and can be reactivated upon anti-retroviral therapy interruption. One of these reservoirs are latently HIV-infected macrophages. Here, we show that HIV infection of macrophages results in survival of a small population of infected cells that are metabolically altered and characterized by mitochondrial fusion, lipid accumulation, and reduced mitochondrial ATP production. No changes in glycolysis were detected. Metabolic analysis indicated an essential role of succinate and other TCA metabolites in the tricarboxylic acid (TCA) cycle in mediating lipid accumulation and oxidative phosphorylation (OXPHOS) in the mitochondria. Furthermore, we show that while uninfected and HIV infected macrophages use fatty acids and glucose as primary sources of energy, surviving HIV infected macrophages also use glutamine/glutamate as a major energy source, and blocking these new sources of energy resulted in the killing of latent HIV infected macrophages. Together, our data provide a new understanding of the formation, properties, and potential novel ways to eliminate macrophage viral reservoirs.
Application of Electrochemical Techniques for Determining and Extracting Natural Product (EgCg) by the Synthesized Conductive Polymer Electrode (Ppy/Pan/rGO) Impregnated with Nano-Particles of TiO2
Authors: Ferdosian Fatemeh , Ebadi Mehdi , Mehrabian Ramin Z. , Golsefidi Maziar A. , Moradi Ali V. 
Published: March 2019

AbstractThe polypyrrole/polyaniline-based electrode (Ppy/Pan/TiO2/rGO) was fabricated via the electrophoretic deposition technique on fluorine-doped tin oxide (FTO)-coated glass. Physico-electrochemical adsorption/desorption of epigallocatechin gallate (EgCg) as an electroactive species was enhanced by the fabricated electrode compared to the electroless technique extraction using the same electrode. EgCg was electrochemically extracted using chronoamperometry by electrophoretically deposited Ppy/Pan/TiO2/rGO film. Isolated EgCg was qualified and quantified by the voltammetry and high-performance liquid chromatography (HPLC) techniques. It was found that the extracted EgCg values were 3.38 and 0.72 ppm from a 10 ppm prepared solution using the electrochemically and physically based techniques, respectively. Morphology/elemental analysis and crystal structure of the prepared electrodes were characterized by field emission scanning electron microscopy/energy-dispersive X-ray (FESEM/EDX) and X-ray diffraction (XRD), respectively. The conductivity of the fabricated electrode was investigated by electrochemical impedance spectroscopy (EIS) and was calculated as 1.124 S/cm for the electrophoretically deposited electrodes (EPD).
Sediment delivery of partially-unfrozen loam soil rill by snow/glacier meltwater flow
Authors: Wan Dan , Li Fa-hu , Yu Wu , Chen Chao , Gao Yuan 
Published: March 2019

AbstractErosion of freeze-thaw soil by meltwater from snow/glacier is one of the main erosion types in high altitude or latitude regions. This study aims to experimentally measure soil erosion processes over partially-unfrozen soil slopes in laboratory. The experiments including three slope gradients of 10°, 15°, and 20°, three water flow rates of 1, 2, and 4 L/min (0.06, 0.12, and 0.24 m3/h), and three thawed-soil depths of 1, 2, and 5 cm were conducted to measure sediment concentration and calculate its delivery rate under seven slope lengths of 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, and 6.0 m. The sediment delivery rates from nonfrozen soil slopes under the corresponding slope gradients, flow rates, and slope lengths also were measured as control treatments. Results showed that the sediment delivery rate from both partially-unfrozen and nonfrozen soil slopes increased logarithmically with slope length. The sediment delivery rate from partially-unfrozen soil slope increased with the increased slope gradient and meltwater flow rate significantly, and the effect of water flow rate on it was greater than that of slope gradient. The thawed-soil depth did not significantly affect sediment delivery rate. The sediment delivery rate from a partially-unfrozen loamy soil slope averagely was 11.4% smaller than that from nonfrozen soil slope. This study is helpful to understand the erosion process of thawing-soil by meltwater from snow/glacier.
Local release of rapamycin by microparticles delays islet rejection within the anterior chamber of the eye
Authors: Fan Yanliang , Zheng Xiaofeng , Ali Yusuf , Berggren Per-Olof , Loo Say Chye Joachim 
Published: March 2019

AbstractThe anterior chamber of the eye (ACE) has emerged as a promising clinical islet transplantation site because of its multiple advantages over the conventional intra-hepatic portal site. This includes reduced surgical invasiveness and increased islet graft survival rate. It also allows for enhanced accessibility and monitoring of the islets. Although the ACE is initially an immuno-privileged site, this privilege is disrupted once the islet grafts are re-vascularized. Given that the ACE is a confined space, achieving graft immune tolerance through local immunosuppressive drug delivery is therefore feasible. Here, we show that islet rejection in the ACE of mice can be significantly suppressed through local delivery of rapamycin by carefully designed sustained-release microparticles. In this 30-day study, allogeneic islet grafts with blank microparticles were completely rejected 18 days post-transplantation into mice. Importantly, allogeneic islet grafts co-injected with rapamycin releasing microparticles into a different eye of the same recipient were preserved much longer, with some grafts surviving for more than 30 days. Hence, islet allograft survival was enhanced by a localized and prolonged delivery of an immunosuppressive drug. We envisage that this procedure will relieve diabetic transplant recipients from harsh systemic immune suppression, while achieving improved glycemic control and reduced insulin dependence.
ApoE-fragment/Aβ heteromers in the brain of patients with Alzheimer’s disease
Authors: Mouchard Amandine , Boutonnet Marie-Charlotte , Mazzocco Claire , Biendon Nathalie , Macrez Nathalie ,   Neuro-CEB Neuropathology Network
Published: March 2019

AbstractIdentification of endogenous pathological amyloid β peptides (Aβ) forms in the brains of patients with Alzheimer’s disease (AD) is still unclear. In healthy brain, Aβ can associate with Apolipoprotein E (ApoE) which is involved in its metabolism and clearance. In the brain of patients with AD, ApoE is cleaved and produces ApoE fragments. We studied the forms of Aβ and their interaction with the ApoE fragments in post-mortem brains from control and AD patients by western blots and co-immunoprecipitation. Three Aβ-containing peptides and three ApoE fragments were specifically found in the brain of AD patients. Co-immunoprecipitations showed that ApoE fragments and Aβ1–42 peptides are co-partners in heteromers of 18 and 16 kDa while ApoE-fragments and Aβ peptides of 12 kDa did not interact with each other. Formation of the 18 kDa ApoE-fragment/Aβ heteromers is specifically increased in ApoE4 carriers and is a strong brain marker of AD while 16 kDa ApoE-fragment/Aβ and Aβ 12 kDa correlate to memory deficit. These data show that in patients with AD, ApoE fragmentation generates peptides that trap Aβ in the brain. Inhibiting the fragmentation or targeting ApoE fragments could be exploited to define strategies to detect or reverse AD.
Synthesis of Hydroxyapatite with Antibacterial Properties Using a Microwave-Assisted Combustion Method
Authors: Lamkhao Suphatchaya , Phaya Manlika , Jansakun Chutima , Chandet Nopakarn , Thongkorn Kriangkrai , Rujijanagul Gobwute , Bangrak Phuwadol , Randorn Chamnan 
Published: March 2019

AbstractThe prevention of implant-associated infections has been increasing clinically in orthopedic surgery. Hydroxyapatite with antibacterial properties was synthesized using a microwave-assisted combustion method. High crystallinity at low temperature can be achieved using this method. The synthesized hydroxyapatite exhibited a superior clear zone for both Gram-positive and Gram-negative bacteria. Electron spin resonance (ESR) and X-ray photoelectron spectroscopy (XPS) were used for the radical investigation. The application of intelligent ink testing and an antioxidant assay using DPPH reduction were also used to confirm the existence of radicals. These techniques provided data confirming that radicals are responsible for the antibacterial properties. The synthesized antibacterial hydroxyapatite would be a good candidate for the prevention any infection with medical implants and injection materials causing failure in bone repair.
Transcriptomics of cytokinin and auxin metabolism and signaling genes during seed maturation in dormant and non-dormant wheat genotypes
Authors: Tuan Pham Anh , Yamasaki Yuji , Kanno Yuri , Seo Mitsunori , Ayele Belay T. 
Published: March 2019

AbstractTo gain insights into the roles of cytokinin (CK) and auxin in regulating dormancy during seed maturation in wheat, we examined changes in the levels of CK and indole-3-acetic acid (IAA) and expression patterns of their metabolism and signaling genes in embryonic and endospermic tissues of dormant and non-dormant genotypes. Seed maturation was associated with a decrease in the levels of isopentenyladenine in both tissues mainly via repression of the CK biosynthetic TaLOG genes. Differential embryonic trans-zeatin content and expression patterns of the CK related genes including TacZOG, TaGLU and TaARR12 between maturing seeds of the two genotypes implicate CK in the control of seed dormancy induction and maintenance. Seed maturation induced a decrease of IAA level in both tissues irrespective of genotype, and this appeared to be mediated by repression of specific IAA biosynthesis, transport and IAA-conjugate hydrolysis genes. The differential embryonic IAA content and expression pattern of the IAA biosynthetic gene TaAO during the early stage of seed maturation between the two genotypes imply the role of IAA in dormancy induction. It appears from our data that the expression of specific auxin signaling genes including TaRUB, TaAXR and TaARF mediate the role of auxin signaling in dormancy induction and maintenance during seed maturation in wheat.
Fine particulate matter (PM2.5) inhibits ciliogenesis by increasing SPRR3 expression via c-Jun activation in RPE cells and skin keratinocytes
Authors: Bae Ji-Eun , Choi Hyunjung , Shin Dong Woon , Na Hye-Won , Park Na Yeon , Kim Joon Bum , Jo Doo Sin , Cho Min Ji , Lyu Jung Ho , Chang Jeong Ho , Lee Eunjoo H. , Lee Tae Ryong , Kim Hyoung-June , Cho Dong-Hyung 
Published: March 2019

AbstractExposure to fine particulate matter (PM) with diameter <2.5 µm (PM2.5) causes epithelium injury and endothelial dysfunction. Primary cilia are sensory organelles that transmit extracellular signals into intracellular biochemical responses and have roles in physiology. To date, there have been no studies investigating whether PM2.5 affects primary cilia in skin. We addressed this in the present study using normal human epidermal keratinocytes (NHEKs) and retinal pigment epithelium (RPE) cells. We found that formation of primary cilium is increased in differentiated NHEKs. However, treatment with PM2.5 blocked increased ciliogenesis in NHEKs and RPE cells. Furthermore, PM2.5 transcriptionally upregulated small proline rich protein 3 (SPRR3) expression by activating c-Jun, and ectopic expression of SPRR3 inhibits suppressed the ciliogenesis. Accordingly, treatment with c-Jun activator (anisomycin) induced SPRR3 expression, whereas the inhibitor (SP600125) recovered the ciliated cells and cilium length in PM2.5-treated cells. Moreover, c-Jun inhibitor suppressed upregulation of SPRR3 in PM2.5-treated cells. Taken together, our finding suggested that PM2.5 inhibits ciliogenesis by increasing SPRR3 expression via c-Jun activation in RPE cells and keratinocytes.
Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice
Authors: Acebedo Alvin R. , Suzuki Kentaro , Hino Shinjiro , Alcantara Mellissa C. , Sato Yuki , Haga Hisashi , Matsumoto Ken-ichi , Nakao Mitsuyoshi , Shimamura Kenji , Takeo Toru , Nakagata Naomi , Miyagawa Shinichi , Nishinakamura Ryuichi , Adelstein Robert S. , Yamada Gen 
Published: March 2019

AbstractThe morphogenesis of mammalian embryonic external genitalia (eExG) shows dynamic differences between males and females. In genotypic males, eExG are masculinized in response to androgen signaling. Disruption of this process can give rise to multiple male reproductive organ defects. Currently, mechanisms of androgen-driven sexually dimorphic organogenesis are still unclear. We show here that mesenchymal-derived actomyosin contractility, by MYH10, is essential for the masculinization of mouse eExG. MYH10 is expressed prominently in the bilateral mesenchyme of male eExG. Androgen induces MYH10 protein expression and actomyosin contractility in the bilateral mesenchyme. Inhibition of actomyosin contractility through blebbistatin treatment and mesenchymal genetic deletion induced defective urethral masculinization with reduced mesenchymal condensation. We also suggest that actomyosin contractility regulates androgen-dependent mesenchymal directional cell migration to form the condensation in the bilateral mesenchyme leading to changes in urethral plate shape to accomplish urethral masculinization. Thus, mesenchymal-derived actomyosin contractility is indispensable for androgen-driven urethral masculinization.
Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae
Authors: Yamaguchi Masaya , Goto Kana , Hirose Yujiro , Yamaguchi Yuka , Sumitomo Tomoko , Nakata Masanobu , Nakano Kazuhiko , Kawabata Shigetada 
Published: March 2019

AbstractEvolutionarily conserved virulence factors can be candidate therapeutic targets or vaccine antigens. Here, we investigated the evolutionary selective pressures on 16 pneumococcal choline-binding cell-surface proteins since Streptococcus pneumoniae is one of the pathogens posing the greatest threats to human health. Phylogenetic and molecular analyses revealed that cbpJ had the highest codon rates to total numbers of codons under considerable negative selection among those examined. Our in vitro and in vivo assays indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing. Deficiency of cbpL under relaxed selective pressure also caused a similar tendency but showed no significant difference in mouse intranasal infection. Thus, molecular evolutionary analysis is a powerful tool that reveals the importance of virulence factors in real-world infection and transmission, since calculations are performed based on bacterial genome diversity following transmission of infection in an uncontrolled population.
Lanthanides compete with calcium for binding to cadherins and inhibit cadherin-mediated cell adhesion
Authors: Brayshaw Lewis L , Smith Rosanna C G , Badaoui Magd , Irving James A , Price Stephen R 
Published: March 2019

Abstract
Lanthanides are rare-earth metals with a broad range of applications in biological research and medicine. In addition to their unique magnetic and spectroscopic properties, lanthanides are also effective mimics of calcium and can stimulate or inhibit the function of calcium-binding proteins. Cadherins are a large family of calcium-binding proteins that facilitate cell adhesion and play key roles in embryo development, tissue homeostasis and tumour metastasis. However, whether lanthanides can bind cadherins and functionally replace calcium binding has not been comprehensively explored. In this study, we investigated the effect of lanthanide binding on cadherin structure and function using terbium, which is a commonly used lanthanide for protein spectroscopy and a proposed anti-cancer agent. We demonstrate that terbium can compete with calcium for binding to calcium-binding sites in cadherins. Terbium binding to cadherins abolished their cell adhesive activity and rendered cadherins sensitive to proteolysis by trypsin. Molecular dynamics simulations indicate that replacement of calcium by terbium results in structural rearrangements and increases the flexibility of the cadherin ectodomain. These changes in structure and dynamics are likely to underlie the inability of lanthanide-bound cadherins to support cell adhesion. Taken together, our findings further knowledge on lanthanide interactions with calcium-binding proteins and provide new insight into the influence of metal chemistry on cadherin structure, dynamics and function.
Integrated analyses of lncRNAs microarray profiles and mRNA–lncRNA coexpression in smooth muscle cells under hypoxic and normoxic conditions
Authors: Zhao Qinshuo , Sun Dating , Li Yuanyuan , Qin Jin , Yan JiangTao 
Published: March 2019

Abstract
Hypoxia may cause abnormal proliferation and migration of the vascular smooth muscle cells (VSMCs) from the media to the intima. This contributes to vessel narrowing and accelerates the process of atherosclerosis. The association of the aberrant expression of long noncoding RNAs (lncRNAs) with the development and progression of atherosclerosis is well known; however, it is not well investigated in hypoxic VSMCs. Using a microarray approach, we identified 1056 and 2804 differentially expressed lncRNAs and mRNAs, respectively, in hypoxic and normoxic mouse aorta smooth muscle (MOVAS) cells. Of them, we randomly chose several lncRNAs and validated the microarray data using the quantitative PCR (qPCR) assay. Advanced bioinformatics analyses indicated that the up-regulated mRNAs were mainly involved in inflammatory responses, lipid metabolism, clearance of amyloid-β peptide, citrate cycle (TCA cycle), TGF-β signaling, and chemokine signaling. The down-regulated mRNAs were mainly involved in the apoptosis pathway, glycerolipid metabolism, Wnt signaling pathway, and MAPK signaling pathway. The constructed coexpression network indicated interactions between 87 lncRNAs and ten mRNAs. In addition, we demonstrated that the silence of lncRNA NONMMUT002434 expression could abrogate the migration and proliferation of smooth muscle cells dramatically. Our data provide comprehensive evidence on the differential expression of lncRNAs and mRNAs in hypoxic MOVAS cells, which may be valuable biomarkers for atherosclerotic diseases, and thereby facilitating diagnosis of atherosclerosis.
On fitness: how do mutations shape the biology of cancer?
Authors: Majewski Ian J. 
Published: March 2019

Abstract
The theory of evolution by natural selection shapes our understanding of the living world. While natural selection has given rise to all the intricacies of life on the planet, those responsible for treating cancer have a darker view of adaptation and selection. Revolutionary changes in DNA sequencing technology have allowed us to survey the complexities that constitute the cancer genome, while advances in genetic engineering are allowing us to functionally interrogate these alterations. These approaches are providing new insights into how mutations influence cancer biology. It is possible that with time, this new knowledge will allow us to take control of the evolutionary processes that shape the disease, to develop more effective treatments.