bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual role of YM1+ M2 macrophages in allergic lung inflammation
Authors: Draijer Christina , Robbe Patricia , Boorsma Carian E. , Hylkema Machteld N. , Melgert Barbro N. 
Published: March 2018

AbstractAlternatively activated (M2 or YM1+) macrophages have been associated with the development of asthma but their contribution to disease initiation and progression remains unclear. To assess the therapeutic potential of modulating these M2 macrophages, we have studied inhibition of M2 polarisation during and after development of allergic lung inflammation by treating with cynaropicrin, a galectin-3 pathway inhibitor. Mice that were treated with this inhibitor of M2 polarisation during induction of allergic inflammation developed less severe eosinophilic lung inflammation and less collagen deposition around airways, while the airway α-smooth muscle actin layer was unaffected. When we treated with cynaropicrin after induction of inflammation, eosinophilic lung inflammation and collagen deposition were also inhibited though to a lesser extent. Unexpectedly, both during and after induction of allergic inflammation, inhibition of M2 polarisation resulted in a shift towards neutrophilic inflammation. Moreover, airway hyperresponsiveness was worse in mice treated with cynaropicrin as compared to allergic mice without inhibitor. These results show that M2 macrophages are associated with remodeling and development of eosinophilic lung inflammation, but prevent development of neutrophilic lung inflammation and worsening of airway hyperresponsiveness. This study suggests that macrophages contribute to determining development of eosinophilic or neutrophilic lung inflammation in asthma.
Three-dimensional Epigenome Statistical Model: Genome-wide Chromatin Looping Prediction
Authors: Al Bkhetan Ziad , Plewczynski Dariusz 
Published: March 2018

AbstractThis study aims to understand through statistical learning the basic biophysical mechanisms behind three-dimensional folding of epigenomes. The 3DEpiLoop algorithm predicts three-dimensional chromatin looping interactions within topologically associating domains (TADs) from one-dimensional epigenomics and transcription factor profiles using the statistical learning. The predictions obtained by 3DEpiLoop are highly consistent with the reported experimental interactions. The complex signatures of epigenomic and transcription factors within the physically interacting chromatin regions (anchors) are similar across all genomic scales: genomic domains, chromosomal territories, cell types, and different individuals. We report the most important epigenetic and transcription factor features used for interaction identification either shared, or unique for each of sixteen (16) cell lines. The analysis shows that CTCF interaction anchors are enriched by transcription factors yet deficient in histone modifications, while the opposite is true in the case of RNAP II mediated interactions. The code is available at the repository https://bitbucket.org/4dnucleome/3depiloop.
Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis
Authors: Asao Rin , Seki Takuto , Takagi Miyuki , Yamada Hiroyuki , Kodama Fumiko , Hosoe-Nagai Yoshiko , Tanaka Eriko , Trejo Juan Alejandro Oliva , Yamamoto-Nonaka Kanae , Sasaki Yu , Hidaka Teruo , Ueno Takashi , Yanagita Motoko , Suzuki Yusuke , Tomino Yasuhiko , Asanuma Katsuhiko 
Published: March 2018

AbstractRac1, a Rho family member, is ubiquitously expressed and participates in various biological processes. Rac1 expression is induced early in podocyte injury, but its role in repair is unclear. To investigate the role of Rac1 expression in podocytes under pathological conditions, we used podocyte-specific Rac1 conditional knock-out (cKO) mice administered adriamycin (ADR), which causes nephrosis and glomerulosclerosis. Larger areas of detached podocytes, more adhesion of the GBM to Bowman’s capsule, and a higher ratio of sclerotic glomeruli were observed in Rac1 cKO mice than in control mice, whereas no differences were observed in glomerular podocyte numbers in both groups after ADR treatment. The mammalian target of rapamycin (mTOR) pathway, which regulates the cell size, was more strongly suppressed in the podocytes of Rac1 cKO mice than in those of control mice under pathological conditions. In accordance with this result, the volumes of podocytes in Rac1 cKO mice were significantly reduced compared with those of control mice. Experiments using in vitro ADR-administered Rac1 knockdown podocytes also supported that a reduction in Rac1 suppressed mTOR activity in injured podocytes. Taken together, these data indicate that Rac1-associated mTOR activation in podocytes plays an important role in preventing the kidneys from developing glomerulosclerosis.
Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity
Authors: Kinyua Ann W. , Doan Khanh V. , Yang Dong Joo , Huynh My Khanh Q. , Choi Yun-Hee , Shin Dong Min , Kim Ki Woo 
Published: March 2018

AbstractDevelopment of metabolic syndrome is associated with hyperactivity of the HPA axis characterized by elevated levels of circulating adrenal hormones including cortisol and aldosterone. However, the molecular mechanism leading to the dysregulation of the HPA axis is not well elucidated. In this study, we found that insulin regulates adrenal steroidogenesis by increasing the expression and activity of steroidogenic factor 1 (SF-1) both in vitro and in vivo and this insulin effect was partly through inhibition of FoxO1. Specifically, insulin increased the protein and RNA levels of SF-1 and steroidogenic target genes. Further, adrenal SF-1 expression was significantly increased by hyperactivation of insulin signaling in mice. Together with the elevated SF-1 expression in adrenal glands, hyperactivation of insulin signaling led to increased aldosterone and corticosterone levels. On the other hand, suppressing the insulin signaling using streptozotocin markedly reduced the expression of adrenal SF-1 in mice. In addition, overexpression of FoxO1 significantly suppressed SF-1 and its steroidogenic target genes implying that the positive effect of insulin on SF-1 activity might be through suppression of FoxO1 in the adrenal gland. Taken together, these results indicate that insulin regulates adrenal steroidogenesis through coordinated control of SF-1 and FoxO1.
Scale-up and large-scale production of Tetraselmis sp. CTP4 (Chlorophyta) for CO2 mitigation: from an agar plate to 100-m3 industrial photobioreactors
Authors: Pereira Hugo , Páramo Jaime , Silva Joana , Marques Ana , Barros Ana , Maurício Dinis , Santos Tamára , Schulze Peter , Barros Raúl , Gouveia Luísa , Barreira Luísa , Varela João 
Published: March 2018

AbstractIndustrial production of novel microalgal isolates is key to improving the current portfolio of available strains that are able to grow in large-scale production systems for different biotechnological applications, including carbon mitigation. In this context, Tetraselmis sp. CTP4 was successfully scaled up from an agar plate to 35- and 100-m3 industrial scale tubular photobioreactors (PBR). Growth was performed semi-continuously for 60 days in the autumn-winter season (17th October – 14th December). Optimisation of tubular PBR operations showed that improved productivities were obtained at a culture velocity of 0.65–1.35 m s−1 and a pH set-point for CO2 injection of 8.0. Highest volumetric (0.08 ± 0.01 g L−1 d−1) and areal (20.3 ± 3.2 g m−2 d−1) biomass productivities were attained in the 100-m3 PBR compared to those of the 35-m3 PBR (0.05 ± 0.02 g L−1 d−1 and 13.5 ± 4.3 g m−2 d−1, respectively). Lipid contents were similar in both PBRs (9–10% of ash free dry weight). CO2 sequestration was followed in the 100-m3 PBR, revealing a mean CO2 mitigation efficiency of 65% and a biomass to carbon ratio of 1.80. Tetraselmis sp. CTP4 is thus a robust candidate for industrial-scale production with promising biomass productivities and photosynthetic efficiencies up to 3.5% of total solar irradiance.
Inhibitory effect of surface pre-reacted glass-ionomer (S-PRG) eluate against adhesion and colonization by Streptococcus mutans
Authors: Nomura Ryota , Morita Yumiko , Matayoshi Saaya , Nakano Kazuhiko 
Published: March 2018

AbstractSurface Pre-reacted Glass-ionomer (S-PRG) filler is a bioactive filler produced by PRG technology, which has been applied to various dental materials. A S-PRG filler can release multiple ions from a glass-ionomer phase formed in the filler. In the present study, detailed inhibitory effects induced by S-PRG eluate (prepared with S-PRG filler) against Streptococcus mutans, a major pathogen of dental caries, were investigated. S-PRG eluate effectively inhibited S. mutans growth especially in the bacterium before the logarithmic growth phase. Microarray analysis was performed to identify changes in S. mutans gene expression in the presence of the S-PRG eluate. The S-PRG eluate prominently downregulated operons related to S. mutans sugar metabolism, such as the pdh operon encoding the pyruvate dehydrogenase complex and the glg operon encoding a putative glycogen synthase. The S-PRG eluate inhibited several in vitro properties of S. mutans relative to the development of dental caries especially prior to active growth. These results suggest that the S-PRG eluate may effectively inhibit the bacterial growth of S. mutans following downregulation of operons involved in sugar metabolism resulting in attenuation of the cariogenicity of S. mutans, especially before the active growth phase.
S-Nitrosoglutathione Reductase Underlies the Dysfunctional Relaxation to Nitric Oxide in Preterm Labor
Authors: Barnett Scott D. , Smith Christina R. , Ulrich Craig C. , Baker Josh E. , Buxton Iain L. O. 
Published: March 2018

AbstractTocolytics show limited efficacy to prevent preterm delivery. In uterine smooth muscle cGMP accumulation following addition of nitric oxide (NO) has little effect on relaxation suggesting a role for protein S-nitrosation. In human myometrial tissues from women in labor at term (TL), or spontaneously in labor preterm (sPTL), direct stimulation of soluble guanylyl cyclase (sGC) fails to relax myometrium, while the same treatment relaxes vascular smooth muscle completely. Unlike term myometrium, effects of NO are not only blunted in sPTL, but global protein S-nitrosation is also diminished, suggesting a dysfunctional response to NO-mediated protein S-nitrosation. Examination of the enzymatic regulator of endogenous S-nitrosoglutathione availability, S-nitrosoglutathione reductase, reveals increased expression of the reductase in preterm myometrium associated with decreased total protein S-nitrosation. Blockade of S-nitrosoglutathione reductase relaxes sPTL tissue. Addition of NO donor to the actin motility assay attenuates force. Failure of sGC activation to mediate relaxation in sPTL tissues, together with the ability of NO to relax TL, but not sPTL myometrium, suggests a unique pathway for NO-mediated relaxation in myometrium. Our results suggest that examining the action of S-nitrosation on critical contraction associated proteins central to the regulation of uterine smooth muscle contraction can reveal new tocolytic targets.
MicroRNA-1 suppresses proliferation, migration and invasion by targeting Notch2 in esophageal squamous cell carcinoma
Authors: Liu Wenzhi , Li Mengkao , Chen Xiangming , Zhu Shan , Shi Hailong , Zhang Dawei , Cheng Cheng , Li Baosheng 
Published: March 2018

AbstractMicroRNAs play an important role in the migration and invasion of tumors, and lower expression of microRNA-1 (miR-1) has been proven in a variety of malignant tumors, including esophageal squamous cell carcinoma (ESCC). In this study, we found that miR-1 expression levels in tumor tissues and preoperative serum from esophageal carcinoma patients were lower than those in non-tumorous tissues and healthy volunteers. miR-1 expression in tissues and plasma was closely related to invasion, lymph node metastasis and TNM staging. Additionally, miR-1 expression levels in tissues and plasma were positively correlated. miR-1 inhibited cell proliferation, migration and invasion. Overexpression of miR-1 in ESCC cells reduced Notch2 protein but not mRNA levels, whereas suppression of miR-1 led to an increase in Notch2 protein but not mRNA levels. A dual-luciferase experiment validated that Notch2 was a direct target of miR-1. Introducing Notch2 mRNA into cells over-expressing miR-1 partially abrogated the effects of miR-1 on migration and invasion. Further studies verified that miR-1 regulates EMT signalling pathways directly through Notch2. Therefore, these results confirm that, as a tumor suppressor gene, miR-1 may be a potential tumor marker for the early diagnosis of ESCC and a new drug target.
Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae
Authors: Vedithi Sundeep Chaitanya , Malhotra Sony , Das Madhusmita , Daniel Sheela , Kishore Nanda , George Anuja , Arumugam Shantha , Rajan Lakshmi , Ebenezer Mannam , Ascher David B. , Arnold Eddy , Blundell Tom L. 
Published: March 2018

AbstractTherpoBgene encodes the β subunit of RNA polymerase holoenzyme inMycobacterium leprae (M.leprae). Missense mutations in therpoBgene were identified as etiological factors for rifampin resistance in leprosy. In the present study, we identified mutations corresponding to rifampin resistance in relapsed leprosy cases from three hospitals in southern India which treat leprosy patients. DNA was extracted from skin biopsies of 35 relapse/multidrug therapy non-respondent leprosy cases, and PCR was performed to amplify the 276 bp rifampin resistance-determining region of therpoBgene. PCR products were sequenced, and mutations were identified in four out of the 35 cases at codon positions D441Y, D441V, S437L and H476R. The structural and functional effects of these mutations were assessed in the context of three-dimensional comparative models of wild-type and mutantM.lepraeRNA polymerase holoenzyme (RNAP), based on the recently solved crystal structures of RNAP ofMycobacterium tuberculosis,containing a synthetic nucleic acid scaffold and rifampin. The resistance mutations were observed to alter the hydrogen-bonding and hydrophobic interactions of rifampin and the 5′ ribonucleotide of the growing RNA transcript. This study demonstrates that rifampin-resistant strains ofM.lepraeamong leprosy patients in southern India are likely to arise from mutations that affect the drug-binding site and stability of RNAP.
Giant thermal hysteresis in Verwey transition of single domain Fe3O4 nanoparticles
Authors: Kim Taehun , Lim Sumin , Hong Jaeyoung , Kwon Soon Gu , Okamoto Jun , Chen Zhi Ying , Jeong Jaehong , Kang Soonmin , Leiner Jonathan C. , Lim Jung Tae , Kim Chul Sung , Huang Di Jing , Hyeon Taeghwan , Lee Soonchil , Park Je-Geun 
Published: March 2018

AbstractMost interesting phenomena of condensed matter physics originate from interactions among different degrees of freedom, making it a very intriguing yet challenging question how certain ground states emerge from only a limited number of atoms in assembly. This is especially the case for strongly correlated electron systems with overwhelming complexity. The Verwey transition of Fe3O4 is a classic example of this category, of which the origin is still elusive 80 years after the first report. Here we report, for the first time, that the Verwey transition of Fe3O4 nanoparticles exhibits size-dependent thermal hysteresis in magnetization, 57Fe NMR, and XRD measurements. The hysteresis width passes a maximum of 11 K when the size is 120 nm while dropping to only 1 K for the bulk sample. This behavior is very similar to that of magnetic coercivity and the critical sizes of the hysteresis and the magnetic single domain are identical. We interpret it as a manifestation of charge ordering and spin ordering correlation in a single domain. This work paves a new way of undertaking researches in the vibrant field of strongly correlated electron physics combined with nanoscience.
Integrating Free-Form Nanostructured GRIN Microlenses with Single-Mode Fibers for Optofluidic Systems
Authors: Kasztelanic Rafal , Filipkowski Adam , Anuszkiewicz Alicja , Stafiej Paulina , Stepniewski Grzegorz , Pysz Dariusz , Krzyzak Konrad , Stepien Ryszard , Klimczak Mariusz , Buczynski Ryszard 
Published: March 2018

AbstractWe present both a theoretical and an experimental study of a novel compact lensed fiber system utilizing a nanostructured GRIN lens. The lens can be integrated with an optical fiber, which ensures a unique and efficient focusing in any high index medium, such as a liquid. We use the effective medium approach to design lenses with arbitrary refractive index. To fabricate lenses, we utilize a discrete array of nano-sized rods made of two types of glasses, and apply a standard stack-and-draw fiber drawing technology. The fabricated nanostructured GRIN lenses have a parabolic refractive index profile with a diameter of a standard fiber, very short working distances (55 µm in the air) and a high numerical aperture (NA = 0.16). As a proof-of-concept of the new micro-lensed fiber system, we demonstrate an experiment on optical trapping of micrometer-sized glass beads. We also show that our method is compatible with optical fiber technology and allows for any shape of the refractive index distribution in 2D. Thanks to that a new functionality could be achieved by replacing the GRIN lens with an axicon lens, vortex type elements, micro-lenses arrays or diffraction elements.
In vivo depletion of serum IgG by an affibody molecule binding the neonatal Fc receptor
Authors: Seijsing Johan , Yu Shengze , Frejd Fredrik Y , Höiden-Guthenberg Ingmarie , Gräslund Torbjörn 
Published: March 2018

AbstractLowering the total level of Immunoglobulin G (IgG) in circulation is a promising general treatment option for many autoimmune diseases driven by pathogenic autoantibodies. The half-life of IgG in circulation is unusually long as a consequence of its interaction with the neonatal Fc receptor (FcRn), which protects it from lysosomal degradation by cells in contact with blood. Blocking the IgG/FcRn interaction prevents FcRn-mediated rescue, which may lead to increased catabolism and a lowering of the total IgG level. Here, we find that an engineered alternative scaffold protein, an affibody molecule, interacting specifically with FcRn, is able to block the IgG/FcRn interaction in vitro. The affibody molecule (ZFcRn) was expressed alone or as a fusion to an albumin binding domain (ABD), to extend its half-life in circulation, in both cases with retained affinity and blocking potential. Repeated i.v. injections in mice of ZFcRn and ZFcRn-ABD were found to result in an up to 40% reduction of the IgG serum-level after 5 days. Potential applications of ZFcRn as a general treatment modality for autoimmune diseases are discussed.
Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal cerebral ischemia
Authors: Tu Ranran , Armstrong Jillian , Lee Kin Sing Stephen , Hammock Bruce D. , Sapirstein Adam , Koehler Raymond C. 
Published: March 2018

AbstractEpoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 epoxygenases from arachidonic acid, and their rapid metabolism is mainly through soluble epoxide hydrolase (sEH). EETs exert vasodilatory, anti-inflammatory, anti-apoptotic, and pro-angiogenic effects. Administration of sEH inhibitors before or at the onset of stroke is protective, but the effects of post-treatment at reperfusion, when inflammation is augmented, has not been as well studied. We tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and protects the brain when administered at reperfusion. Vehicle or 1 mg/kg TPPU was administered at reperfusion after 90 minutes of focal ischemia and again 24 hours later. Protein expression and activity of sEH increased after reperfusion and activity was decreased by TPPU administration. TPPU decreased infarct volume by 50%, reduced neurologic deficits and improved performance on sensorimotor tasks. Furthermore, TPPU significantly lowered the mRNA expression of interleukin-1beta by 3.5-fold and tumor necrosis factor-alpha by 2.2-fold, increased transforming growth factor-beta mRNA by 1.8-fold, and augmented immunostaining of vascular endothelial growth factor in peri-infarct cortex. Thus, inhibition of sEH at reperfusion significantly reduces infarction and improves sensorimotor function, possibly by suppressing early proinflammatory cytokines and promoting reparative cytokines and growth factors.
Concurrent action of purifying selection and gene conversion results in extreme conservation of the major stress-inducible Hsp70 genes in mammals
Authors: Hess Kyle , Oliverio Ryan , Nguyen Peter , Le Dat , Ellis Jacqueline , Kdeiss Brianna , Ord Sara , Chalkia Dimitra , Nikolaidis Nikolas 
Published: March 2018

AbstractSeveral evolutionary mechanisms alter the fate of mutations and genes within populations based on their exhibited functional effects. To understand the underlying mechanisms involved in the evolution of the cellular stress response, a very conserved mechanism in the course of organismal evolution, we studied the patterns of natural genetic variation and functional consequences of polymorphisms of two stress-inducible Hsp70 genes. These genes, HSPA1A and HSPA1B, are major orchestrators of the cellular stress response and are associated with several human diseases. Our phylogenetic analyses revealed that the duplication of HSPA1A and HSPA1B originated in a lineage proceeding to placental mammals, and henceforth they remained in conserved synteny. Additionally, analyses of synonymous and non-synonymous changes suggest that purifying selection shaped the HSPA1 gene diversification, while gene conversion resulted in high sequence conservation within species. In the human HSPA1-cluster, the vast majority of mutations are synonymous and specific genic regions are devoid of mutations. Furthermore, functional characterization of several human polymorphisms revealed subtle differences in HSPA1A stability and intracellular localization. Collectively, the observable patterns of HSPA1A-1B variation describe an evolutionary pattern, in which purifying selection and gene conversion act simultaneously and conserve a major orchestrator of the cellular stress response.
The effects of hydroxyethyl starch and gelatine on pulmonary cytokine production and oedema formation
Authors: Krabbe Julia , Ruske Nadine , Braunschweig Till , Kintsler Svetlana , Spillner Jan W. , Schröder Thomas , Kalverkamp Sebastian , Kanzler Stephanie , Rieg Annette D. , Uhlig Stefan , Martin Christian 
Published: March 2018

AbstractRecently, side effects of plasma expanders like hydroxyethyl starch and gelatine gained considerable attention. Most studies have focused on the kidneys; lungs remain unconsidered. Isolated mouse lungs were perfused for 4 hours with buffer solutions based on hydroxyethyl starch (HES) 130/0.4, HES 200/0.5 or gelatine and ventilated with low or high pressure under physiological pH and alkalosis. Outcome parameters were cytokine levels and the wet-to-dry ratio. For cytokine release, murine and human PCLS were incubated in three different buffers and time points.In lungs perfused with the gelatine based buffer IL-6, MIP-2 and KC increased when ventilated with high pressure. Wet-to-dry ratios increased stronger in lungs perfused with gelatine - compared to HES 130/0.4. Alkalotic perfusion resulted in higher cytokine levels but normal wet-to-dry ratio. Murine PCLS supernatants showed increased IL-6 and KC when incubated in gelatine based buffer, whereas in human PCLS IL-8 was elevated. In murine IPL HES 130/0.4 has lung protective effects in comparison to gelatine based infusion solutions, especially in the presence of high-pressure ventilation. Gelatine perfusion resulted in increased cytokine production. Our findings suggest that gelatine based solutions may have side effects in patients with lung injury or lung oedema.