bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2
Authors: Wang Zhiding , Sun Dejun , Chen Guojiang , Li Ge , Dou Shuaijie , Wang Renxi , Xiao He , Hou Chunmei , Li Yan , Feng Jiannan , Shen Beifen , Han Gencheng 
Published: February 2017

AbstractT cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation. CD36 and heme oxygenase-1 (HO-1), two downstream molecules in the Tim-3-Nrf2 signaling axis, are involved in the Tim-3- mediated immune evasion of L. monocytogenes both in vitro and in vivo. We here identified new mechanisms by which Tim-3 induces infection tolerance. By modulating the Tim-3 pathway, we demonstrate the feasibility of manipulating macrophage function as a potent tool for treating infectious diseases, such as Listeria infection.
Imaging cardiac SCN5A using the novel F-18 radiotracer radiocaine
Authors: Hooker Jacob M. , Strebl Martin G. , Schroeder Frederick A. , Wey Hsiao-Ying , Ambardekar Amrut V. , McKinsey Timothy A. , Schoenberger Matthias 
Published: February 2017

AbstractThe key function of the heart, a well-orchestrated series of contractions, is controlled by cardiac action potentials. These action potentials are initiated and propagated by a single isoform of voltage gated sodium channels – SCN5A. However, linking changes in SCN5A expression levels to human disease in vivo has not yet been possible. Radiocaine, an F-18 radiotracer for positron emission tomography (PET), is the first SCN5A imaging agent in the heart. Explants from healthy and failing human hearts were compared using radiocaine autoradiography to determine that the failing heart has ~30% lower SCN5A levels - the first evidence of changes in SCN5A expression in humans as a function of disease. Paving the way for translational imaging, radiocaine proved to exhibit high in vivo specific binding to the myocardium of non-human primates. We envision that SCN5A measurements using PET imaging may serve as a novel diagnostic tool to stratify arrhythmia risk and assess for progression of heart failure in patients with a broad spectrum of cardiovascular diseases.
PAK4 interacts with p85 alpha: implications for pancreatic cancer cell migration
Authors: King Helen , Thillai Kiruthikah , Whale Andrew , Arumugam Prabhu , Eldaly Hesham , Kocher Hemant M. , Wells Claire M. 
Published: February 2017

AbstractIt has been reported that p21-activated kinase 4 (PAK4) is amplified in pancreatic cancer tissue. PAK4 is a member of the PAK family of serine/threonine kinases, which act as effectors for several small GTPases, and has been specifically identified to function downstream of HGF-mediated c-Met activation in a PI3K dependent manner. However, the functionality of PAK4 in pancreatic cancer and the contribution made by HGF signalling to pancreatic cancer cell motility remain to be elucidated. We now find that elevated PAK4 expression is coincident with increased expression levels of c-Met and the p85α subunit of PI3K. Furthermore, we demonstrate that pancreatic cancer cells have a specific motility response to HGF both in 2D and 3D physiomimetic organotypic assays; which can be suppressed by inhibition of PI3K. Significantly, we report a specific interaction between PAK4 and p85α and find that PAK4 deficient cells exhibit a reduction in Akt phosphorylation downstream of HGF signalling. These results implicate a novel role for PAK4 within the PI3K pathway via interaction with p85α. Thus, PAK4 could be an essential player in PDAC progression representing an interesting therapeutic opportunity.
Dependence On Glycolysis Sensitizes BRAF-mutated Melanomas For Increased Response To Targeted BRAF Inhibition
Authors: Hardeman Keisha N. , Peng Chengwei , Paudel Bishal B. , Meyer Christian T. , Luong Thong , Tyson Darren R. , Young Jamey D. , Quaranta Vito , Fessel Joshua P. 
Published: February 2017

AbstractDysregulated metabolism can broadly affect therapy resistance by influencing compensatory signaling and expanding proliferation. Given many BRAF-mutated melanoma patients experience disease progression with targeted BRAF inhibitors, we hypothesized therapeutic response is related to tumor metabolic phenotype, and that altering tumor metabolism could change therapeutic outcome. We demonstrated the proliferative kinetics of BRAF-mutated melanoma cells treated with the BRAF inhibitor PLX4720 fall along a spectrum of sensitivity, providing a model system to study the interplay of metabolism and drug sensitivity. We discovered an inverse relationship between glucose availability and sensitivity to BRAF inhibition through characterization of metabolic phenotypes using nearly a dozen metabolic parameters in Principle Component Analysis. Subsequently, we generated rho0 variants that lacked functional mitochondrial respiration and increased glycolytic metabolism. The rho0 cell lines exhibited increased sensitivity to PLX4720 compared to the respiration-competent parental lines. Finally, we utilized the FDA-approved antiretroviral drug zalcitabine to suppress mitochondrial respiration and to force glycolysis in our cell line panel, resulting in increased PLX4720 sensitivity via shifts in EC50 and Hill slope metrics. Our data suggest that forcing tumor glycolysis in melanoma using zalcitabine or other similar approaches may be an adjunct to increase the efficacy of targeted BRAF therapy.
A large-scale survey on sharp injuries among hospital-based healthcare workers in China
Authors: Gao Xiaodong , Hu Bijie , Suo Yao , Lu Qun , Chen Baiyi , Hou Tieying , Qin Jin’ai , Huang Wenzhi , Zong Zhiyong 
Published: February 2017

AbstractA multi-center survey on sharp injuries (SIs) among hospital-based healthcare workers (HCWs) in seven provinces of China between August and December 2011 was performed. In each province, HCWs from at least 30 hospitals were surveyed by completing a SI report form adapted from the EPINet. The HCWs who declared SIs during the period were interviewed by local infection control practitioners. The survey included 361 hospitals and 206,711 HCWs, most of whom were nurses (47.5%) or doctors (28.4%). In the previous month, 17,506 SI incidents were declared by 13,110 (6.3%) HCWs, corresponding to 1,032 incidents per 1,000 HCWs per year and 121.3 per 100 occupied beds per year. The majority of the SIs was caused by a hollow-bore needle (63.0%). The source patient was identified in 73.4% of all SIs but only 4.4% of all exposures involved a source patient who tested positive for HBV (3.3%), HCV (0.4%) or HIV (0.1%). Only 4.6% of SIs were reported to the infection control team in the hospitals. In conclusion, the rate of SI among HCWs is high in China and SI represents a severe but largely neglected problem. Awareness and safety climate should be promoted to protect the safety of HCWs in China.
Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis
Authors: Li Na , Zhang Jun , Liao Dan , Yang Lu , Wang Yingxiong , Hou Shengping 
Published: February 2017

AbstractAlthough several studies have investigated the association between C4, C4A, and C4B gene copy number variations (CNVs) and susceptibility to autoimmune diseases, the results remain inconsistency for those diseases. Thus, in this study, a comprehensive meta-analysis was conducted to assess the role of C4, C4A, and C4B CNVs in autoimmune diseases in different ethnic groups. A total of 16 case-control studies described in 12 articles (8663 cases and 11099 controls) were included in this study. The pooled analyses showed that a low C4 gene copy number (GCN) (<4) was treated as a significant risk factor (odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.19–1.78) for autoimmune diseases compared with a higher GCN (>4). The pooled statistical results revealed that low C4 (<4) and low C4A (<2) GCNs could be risk factors for systemic lupus erythematosus (SLE) in Caucasian populations. Additionally, the correlation between C4B CNVs and all type of autoimmune diseases could not be confirmed by the current meta-analysis (OR = 1.07, 95% CI = 0.93–1.24). These data suggest that deficiency or absence of C4 and C4A CNVs may cause susceptibility to SLE.
High Sensitivity Terahertz Detection through Large-Area Plasmonic Nano-Antenna Arrays
Authors: Yardimci Nezih Tolga , Jarrahi Mona 
Published: February 2017

AbstractPlasmonic photoconductive antennas have great promise for increasing responsivity and detection sensitivity of conventional photoconductive detectors in time-domain terahertz imaging and spectroscopy systems. However, operation bandwidth of previously demonstrated plasmonic photoconductive antennas has been limited by bandwidth constraints of their antennas and photoconductor parasitics. Here, we present a powerful technique for realizing broadband terahertz detectors through large-area plasmonic photoconductive nano-antenna arrays. A key novelty that makes the presented terahertz detector superior to the state-of-the art is a specific large-area device geometry that offers a strong interaction between the incident terahertz beam and optical pump at the nanoscale, while maintaining a broad operation bandwidth. The large device active area allows robust operation against optical and terahertz beam misalignments. We demonstrate broadband terahertz detection with signal-to-noise ratio levels as high as 107 dB.
Leukocyte TLR5 deficiency inhibits atherosclerosis by reduced macrophage recruitment and defective T-cell responsiveness
Authors: Ellenbroek Guilielmus H.J.M. , van Puijvelde Gijs H.M. , Anas Adam A. , Bot Martine , Asbach Miriam , Schoneveld Arjan , van Santbrink Peter J. , Foks Amanda C. , Timmers Leo , Doevendans Pieter A. , Pasterkamp Gerard , Hoefer Imo E. , van der Poll Tom , Kuiper Johan , de Jager Saskia C.A. 
Published: February 2017

AbstractToll-like receptors (TLR) provide a critical link between innate and adaptive immunity, both important players in atherosclerosis. Since evidence for the role of TLR5 is lacking, we aimed to establish this in the immune axis of atherosclerosis. We assessed the effect of the TLR5-specific ligand Flagellin on macrophage maturation and T-cell polarisation. Next, we generated TLR5−/−LDLr−/− chimeras to study the effect of hematopoietic TLR5 deficiency on atherosclerosis formation. Flagellin stimulation did not influence wildtype or TLR5−/− macrophage maturation. Only in wildtype macrophages, Flagellin exposure increased MCP-1 and IL6 expression. Flagellin alone reduced T-helper 1 proliferation, which was completely overruled in the presence of T-cell receptor activation. In vivo, hematopoietic TLR5 deficiency attenuated atherosclerotic lesion formation by ≈25% (1030*103 ± 63*103 vs. 792*103 ± 61*103 μm2; p = 0.013) and decreased macrophage area (81.3 ± 12.0 vs. 44.2 ± 6.6 μm2; p = 0.011). In TLR5−/− chimeric mice, we observed lower IL6 plasma levels (36.4 ± 5.6 vs. 15.1 ± 2.2 pg/mL; p = 0.003), lower (activated) splenic CD4+ T-cell content (32.3 ± 2.1 vs. 21.0 ± 1.2%; p = 0.0018), accompanied by impaired T-cell proliferative responses. In conclusion, hematopoietic TLR5 deficiency inhibits atherosclerotic lesion formation by attenuated macrophage accumulation and defective T-cell responsiveness.
In situ observation of macroscopic phase separation in cobalt hexacyanoferrate film
Authors: Takachi Masamitsu , Moritomo Yutaka 
Published: February 2017

AbstractLithium-ion secondary batteries (LIBs) store electric energy via Li+ deintercalation from cathode materials. The Li+ deintercalation frequently drives a first-order phase transition of the cathode material as a result of the Li-ordering or Li-concentration effect and causes a phase separation (PS) into the Li-rich and Li-poor phases. Here, we performed an in situ microscopic investigation of the PS dynamics in thin films of cobalt hexacyanoferrate, LixCo[Fe(CN)6]0.9, against Li+ deintercalation. The thick film (d = 1.5 μm) shows a characteristic macroscopic PS of several tens of μm into the green (Li1.6Co[Fe(CN)6]0.9) and black (Li.6Co[Fe(CN)6]0.9) phases in the x range of 1.0 < x < 1.6. Reflecting the substrate strain, the thin film (d = 0.5 μm) shows no trace of the PS in the entire x region. Our observation suggests that the macroscopic PS plays a significant role in the charge/discharge dynamics of the cathode.
Octreotide Attenuates Acute Kidney Injury after Hepatic Ischemia and Reperfusion by Enhancing Autophagy
Authors: Sun Huiping , Zou Shuangfa , Candiotti Keith A. , Peng Yanhua , Zhang Qinya , Xiao Weiqiang , Wen Yiyun , wu Jiao , Yang Jinfeng 
Published: February 2017

AbstractOctreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat. Octreotide pretreatment significantly preserved renal function and reduced the severity of renal injury. Moreover, octreotide alleviated inflammation and apoptosis in the kidney after HIR. Additionally, octreotide induced autophagy and autophagy inhibition with 3MA markedly reversed the renoprotective, anti-inflammatory and anti-apoptotic effects of octreotide after HIR. Finally, octreotide abrogated the activation of phosphorylation of Akt, mTOR and p70S6K in the kidney after HIR. Our results indicate that octreotide reduced renal injury after HIR due to its induction of autophagy. The enhancement of autophagy may be potentially linked to the octreotide mediated Akt/mTOR/p70S6K pathway deactivation and reduction of kidney inflammation and apoptosis after HIR.
Ontogenetic loops in habitat use highlight the importance of littoral habitats for early life-stages of oceanic fishes in temperate waters
Authors: Polte Patrick , Kotterba Paul , Moll Dorothee , von Nordheim Lena 
Published: February 2017

AbstractGeneral concepts of larval fish ecology in temperate oceans predominantly associate dispersal and survival to exogenous mechanisms such as passive drift along ocean currents. However, for tropical reef fish larvae and species in inland freshwater systems behavioural aspects of habitat selection are evidently important components of dispersal. This study is focused on larval Atlantic herring (Clupea harengus) distribution in a Baltic Sea retention area, free of lunar tides and directed current regimes, considered as a natural mesocosm. A Lorenz curve originally applied in socio-economics to describe demographic income distribution was adapted to a 20 year time-series of weekly larval herring distribution, revealing size-dependent spatial homogeneity. Additional quantitative sampling of distinct larval development stages across pelagic and littoral areas uncovered a loop in habitat use during larval ontogeny, revealing a key role of shallow littoral waters. With increasing rates of coastal change, our findings emphasize the importance of the littoral zone when considering reproduction of pelagic, ocean-going fish species; highlighting a need for more sensitive management of regional coastal zones.
Structural environment built by AKAP12+ colon mesenchymal cells drives M2 macrophages during inflammation recovery
Authors: Yang Jun-Mo , Lee Hye Shin , Seo Ji Hae , Park Ji-Hyeon , Gelman Irwin H. , Lo Eng H. , Kim Kyu-Won 
Published: February 2017

AbstractMacrophages exhibit phenotypic plasticity, as they have the ability to switch their functional phenotypes during inflammation and recovery. Simultaneously, the mechanical environment actively changes. However, how these dynamic alterations affect the macrophage phenotype is unknown. Here, we observed that the extracellular matrix (ECM) constructed by AKAP12+ colon mesenchymal cells (CMCs) generated M2 macrophages by regulating their shape during recovery. Notably, rounded macrophages were present in the linear and loose ECM of inflamed colons and polarized to the M1 phenotype. In contrast, ramified macrophages emerged in the contracted ECM of recovering colons and mainly expressed M2 macrophage markers. These contracted structures were not observed in the inflamed colons of AKAP12 knockout (KO) mice. Consequently, the proportion of M2 macrophages in inflamed colons was lower in AKAP12 KO mice than in WT mice. In addition, clinical symptoms and histological damage were more severe in AKAP12 KO mice than in WT mice. In experimentally remodeled collagen gels, WT CMCs drove the formation of a more compacted structure than AKAP12 KO CMCs, which promoted the polarization of macrophages toward an M2 phenotype. These results demonstrated that tissue contraction during recovery provides macrophages with the physical cues that drive M2 polarization.
In Vitro Characterization and Concerted Function of Three Core Enzymes of a Glycyl Radical Enzyme - Associated Bacterial Microcompartment
Authors: Zarzycki Jan , Sutter Markus , Cortina Niña Socorro , Erb Tobias J. , Kerfeld Cheryl A. 
Published: February 2017

AbstractMany bacteria encode proteinaceous bacterial microcompartments (BMCs) that encapsulate sequential enzymatic reactions of diverse metabolic pathways. Well-characterized BMCs include carboxysomes for CO2-fixation, and propanediol- and ethanolamine-utilizing microcompartments that contain B12-dependent enzymes. Genes required to form BMCs are typically organized in gene clusters, which promoted their distribution across phyla by horizontal gene transfer. Recently, BMCs associated with glycyl radical enzymes (GREs) were discovered; these are widespread and comprise at least three functionally distinct types. Previously, we predicted one type of these GRE-associated microcompartments (GRMs) represents a B12-independent propanediol-utilizing BMC. Here we functionally and structurally characterize enzymes of the GRM of Rhodopseudomonas palustris BisB18 and demonstrate their concerted function in vitro. The GRM signature enzyme, the GRE, is a dedicated 1,2-propanediol dehydratase with a new type of intramolecular encapsulation peptide. It forms a complex with its activating enzyme and, in conjunction with an aldehyde dehydrogenase, converts 1,2-propanediol to propionyl-CoA. Notably, homologous GRMs are also encoded in pathogenic Escherichia coli strains. Our high-resolution crystal structures of the aldehyde dehydrogenase lead to a revised reaction mechanism. The successful in vitro reconstitution of a part of the GRM metabolism provides insights into the metabolic function and steps in the assembly of this BMC.
New evidence from China for the nature of the pterosaur evolutionary transition
Authors: Wang Xiaoli , Jiang Shunxing , Zhang Junqiang , Cheng Xin , Yu Xuefeng , Li Yameng , Wei Guangjin , Wang Xiaolin 
Published: February 2017

AbstractPterosaurs are extinct flying reptiles, the first vertebrates to achieve powered flight. Our understanding of the evolutionary transition between basal, predominantly long-tailed forms to derived short-tailed pterodactyloids remained poor until the discovery ofWukongopterusandDarwinopterusin western Liaoning, China. In this paper we report on a new genus and species,Douzhanopterus zhengi, that has a reduced tail, 173% the length of the humerus, and a reduced fifth pedal digit, whose first phalange is ca. 20% the length of metatarsal III, both unique characters to Monofenestra. The morphological comparisons and phylogenetic analysis presented in this paper demonstrate thatDouzhanopterusis the sister group to the ‘Painten pro-pterodactyloid’ and the Pterodactyloidea, reducing the evolutionary gap between long- and short-tailed pterosaurs.
Polymorphisms of toll-like receptors 2 and 9 and severity and prognosis of bacterial meningitis in Chinese children
Authors: Zhang Pingping , Zhang Nan , Liu Linlin , Zheng Kai , Zhu Liang , Zhu Junping , Cao Lina , Jiang Yiyuan , Liu Gang , He Qiushui 
Published: February 2017

AbstractToll-like receptors (TLRs) play a crucial role in innate immunity, protecting the host from bacterial pathogens. We investigated whether bacterial meningitis (BM) in children was associated with gene polymorphisms in TLR2 (rs3804099), TLR3 (rs3775291 and rs3775290) and TLR9 (rs352139 and rs352140). Blood samples were taken from 218 child patients with confirmed BM and 330 healthy adult controls (HC) and polymorphisms of these genes were analyzed by PCR-based sequencing. For TLR2 rs3804099, frequencies of the minor allele C were markedly higher in patients with severe BM (defined as CSF glucose concentration ≤ 1.5 mmol/L and seizures) than those without (43.5% and 40.1% vs. 30.1% and 29.1%, p = 0.008 and p = 0.016, respectively). For TLR9 rs352139, patients who carried genotype AA and minor allele A developed seizures less often than those without (OR = 0.289, p = 0.003 and OR = 0.568, p = 0.004, respectively). However, for TLR9 rs352140, patients who carried genotype TT and minor allele T developed seizures more often than those without (OR = 3.385, p = 0.004 and OR = 1.767, p = 0.004, respectively). Our finding suggested that genetic variations in TLR2 and TLR9 are associated with severity and prognosis of bacterial meningitis in Chinese children. However, the results should be interpreted with caution since the number of subjects included was limited.
Dynamic control of asymmetric electromagnetic wave transmission by active chiral metamaterial
Authors: Chen Ke , Feng Yijun , Cui Li , Zhao Junming , Jiang Tian , Zhu Bo 
Published: February 2017

AbstractThe asymmetric transmission of electromagnetic (EM) wave can be fully manipulated by chiral metamaterials, but little can achieve real-time and high efficient tunability due to challenges in practically deployable solutions. Here, we proposed a new scheme for flexibly and dynamically controlling the asymmetric EM wave transmission at microwave frequencies using planar metamaterial of deep subwavelength thickness incorporated with active components of PIN diodes. The asymmetric transmission of linearly polarized EM wave exhibits a high efficiency and a pronounced real-time continuous tunability controlled by the external stimulation of voltage biasing. In addition, the asymmetric transmission effect can be well preserved at large oblique incident angle up to ±70°. The design principle and EM performance are validated by both full wave simulations and experimental measurements. Such dynamically controllable chiral metamaterial may provide robust and flexible approach to manipulate EM wave propagation, as well as to facilitate EM device integration to create diverse functionalities.