bluuebunny/crossref_metadata_2025 huggingface dataset:
A generalized quantitative antibody homeostasis model: maintenance of global antibody equilibrium by effector functions
Authors: Prechl József
Published: November 2017

The homeostasis of antibodies can be characterized as a balanced production, target‐binding and receptor‐mediated elimination regulated by an interaction network, which controls B‐cell development and selection. Recently, we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network. Here we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody, free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]=KD. This zone corresponds to the biologically relevant KD range of reversible interactions. We show that thermodynamic and kinetic properties of antibody–antigen interactions correlate with immunological functions. The formation of stable, long‐lived immune complexes correspond to a decrease of entropy and is a prerequisite for the generation of higher‐order complexes. As the energy of formation of complexes increases, we observe a gradual shift from silent clearance to inflammatory reactions. These rules can also be applied to complement activation‐related immune effector processes, linking the physicochemical principles of innate and adaptive humoral responses. Affinity of the receptors mediating effector functions shows a wide range of affinities, allowing the continuous sampling of antibody‐bound antigen over the complete range of concentrations. The generation of multivalent, multicomponent complexes triggers effector functions by crosslinking these receptors on effector cells with increasing enzymatic degradation potential. Thus, antibody homeostasis is a thermodynamic system with complex network properties, nested into the host organism by proper immunoregulatory and effector pathways. Maintenance of global antibody equilibrium is achieved by innate qualitative signals modulating a quantitative adaptive immune system, which regulates molecular integrity of the host by tuning the degradation and recycling of molecules from silent removal to inflammatory elimination.
The molecular basis of phosphite and hypophosphite recognition by ABC-transporters
Authors: Bisson Claudine , Adams Nathan B. P. , Stevenson Ben , Brindley Amanda A. , Polyviou Despo , Bibby Thomas S. , Baker Patrick J. , Hunter C. Neil , Hitchcock Andrew
Published: November 2017

Inorganic phosphate is the major bioavailable form of the essential nutrient phosphorus. However, the concentration of phosphate in most natural habitats is low enough to limit microbial growth. Under phosphate-depleted conditions some bacteria utilise phosphite and hypophosphite as alternative sources of phosphorus, but the molecular basis of reduced phosphorus acquisition from the environment is not fully understood. Here, we present crystal structures and ligand binding affinities of periplasmic binding proteins from bacterial phosphite and hypophosphite ATP-binding cassette transporters. We reveal that phosphite and hypophosphite specificity results from a combination of steric selection and the presence of a P-H…π interaction between the ligand and a conserved aromatic residue in the ligand-binding pocket. The characterisation of high affinity and specific transporters has implications for the marine phosphorus redox cycle, and might aid the use of phosphite as an alternative phosphorus source in biotechnological, industrial and agricultural applications.
An extracellular matrix-related prognostic and predictive indicator for early-stage non-small cell lung cancer
Authors: LIM Su Bin , TAN Swee Jin , LIM Wan-Teck , LIM Chwee Teck
Published: November 2017

The prognosis and prediction of adjuvant chemotherapy (ACT) response in early-stage non-small cell lung cancer (NSCLC) patients remain poor in this era of personalized medicine. We hypothesize that extracellular matrix (ECM)-associated components could be potential markers for better diagnosis and prognosis due to their differential expression in 1,943 primary NSCLC tumors as compared to 303 normal lung tissues. Here we develop a 29-gene ECM-related prognostic and predictive indicator (EPPI). We validate a robust performance of the EPPI risk scoring system in multiple independent data sets, comprising a total of 2,071 early-stage NSCLC tumors. Patients are stratified according to the universal cutoff score based on the EPPI when applied in the clinical setting; the low-risk group has significantly better survival outcome. The functional EPPI gene set represents a potential genomic tool to improve patient selection in early-stage NSCLC to further derive the best benefits of ACT and prevent unnecessary treatment or ACT-associated morbidity.
Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator functions of transcriptional cofactor GRIP1 in macrophages
Authors: Rollins David A. , Kharlyngdoh Joubert B. , Coppo Maddalena , Tharmalingam Bowranigan , Mimouna Sanda , Guo Ziyi , Sacta Maria A. , Pufall Miles A. , Fisher Robert P. , Hu Xiaoyu , Chinenov Yurii , Rogatsky Inez
Published: November 2017

The glucocorticoid (GC) receptor (GR) suppresses inflammation by activating anti-inflammatory and repressing pro-inflammatory genes. GR-interacting protein-1 (GRIP1) is a GR corepressor in macrophages, however, whether GRIP1 mediates GR-activated transcription, and what dictates its coactivator versus corepressor properties is unknown. Here we report that GRIP1 loss in macrophages attenuates glucocorticoid induction of several anti-inflammatory targets, and that GC treatment of quiescent macrophages globally directs GRIP1 toward GR binding sites dominated by palindromic GC response elements (GRE), suggesting a non-redundant GRIP1 function as a GR coactivator. Interestingly, GRIP1 is phosphorylated at an N-terminal serine cluster by cyclin-dependent kinase-9 (CDK9), which is recruited into GC-induced GR:GRIP1:CDK9 hetero-complexes, producing distinct GRE-specific GRIP1 phospho-isoforms. Phosphorylation potentiates GRIP1 coactivator but, remarkably, not its corepressor properties. Consistently, phospho-GRIP1 and CDK9 are not detected at GR transrepression sites near pro-inflammatory genes. Thus, GR restricts actions of its own coregulator via CDK9-mediated phosphorylation to a subset of anti-inflammatory genes.
Receptor-binding loops in alphacoronavirus adaptation and evolution
Authors: Wong Alan H. M. , Tomlinson Aidan C. A. , Zhou Dongxia , Satkunarajah Malathy , Chen Kevin , Sharon Chetna , Desforges Marc , Talbot Pierre J. , Rini James M.
Published: November 2017

RNA viruses are characterized by a high mutation rate, a buffer against environmental change. Nevertheless, the means by which random mutation improves viral fitness is not well characterized. Here we report the X-ray crystal structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV-229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN). Three extended loops are solely responsible for receptor binding and the evolution of HCoV-229E and its close relatives is accompanied by changing loop–receptor interactions. Phylogenetic analysis shows that the natural HCoV-229E receptor-binding loop variation observed defines six RBD classes whose viruses have successively replaced each other in the human population over the past 50 years. These RBD classes differ in their affinity for APN and their ability to bind an HCoV-229E neutralizing antibody. Together, our results provide a model for alphacoronavirus adaptation and evolution based on the use of extended loops for receptor binding.
Skyrmion dynamics in a frustrated ferromagnetic film and current-induced helicity locking-unlocking transition
Authors: Zhang Xichao , Xia Jing , Zhou Yan , Liu Xiaoxi , Zhang Han , Ezawa Motohiko
Published: November 2017

The helicity-orbital coupling is an intriguing feature of magnetic skyrmions in frustrated magnets. Here we explore the skyrmion dynamics in a frustrated magnet based on the J1-J2-J3 classical Heisenberg model explicitly by including the dipole-dipole interaction. The skyrmion energy acquires a helicity dependence due to the dipole-dipole interaction, resulting in the current-induced translational motion with a fixed helicity. The lowest-energy states are the degenerate Bloch-type states, which can be used for building the binary memory. By increasing the driving current, the helicity locking-unlocking transition occurs, where the translational motion changes to the rotational motion. Furthermore, we demonstrate that two skyrmions can spontaneously form a bound state. The separation of the bound state forced by a driving current is also studied. In addition, we show the annihilation of a pair of skyrmion and antiskyrmion. Our results reveal the distinctive frustrated skyrmions may enable viable applications in topological magnetism.
Ultrafast non-radiative dynamics of atomically thin MoSe2
Authors: Lin Ming-Fu , Kochat Vidya , Krishnamoorthy Aravind , Bassman Oftelie Lindsay , Weninger Clemens , Zheng Qiang , Zhang Xiang , Apte Amey , Tiwary Chandra Sekhar , Shen Xiaozhe , Li Renkai , Kalia Rajiv , Ajayan Pulickel , Nakano Aiichiro , Vashishta Priya , Shimojo Fuyuki , Wang Xijie , Fritz David M. , Bergmann Uwe
Published: November 2017

Photo-induced non-radiative energy dissipation is a potential pathway to induce structural-phase transitions in two-dimensional materials. For advancing this field, a quantitative understanding of real-time atomic motion and lattice temperature is required. However, this understanding has been incomplete due to a lack of suitable experimental techniques. Here, we use ultrafast electron diffraction to directly probe the subpicosecond conversion of photoenergy to lattice vibrations in a model bilayered semiconductor, molybdenum diselenide. We find that when creating a high charge carrier density, the energy is efficiently transferred to the lattice within one picosecond. First-principles nonadiabatic quantum molecular dynamics simulations reproduce the observed ultrafast increase in lattice temperature and the corresponding conversion of photoenergy to lattice vibrations. Nonadiabatic quantum simulations further suggest that a softening of vibrational modes in the excited state is involved in efficient and rapid energy transfer between the electronic system and the lattice.
Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2
Authors: Karuppasamy Manikandan , Kusmider Beata , Oliveira Taiana M. , Gaubitz Christl , Prouteau Manoel , Loewith Robbie , Schaffitzel Christiane
Published: November 2017

The target of rapamycin (TOR) kinase assembles into two distinct multiprotein complexes, conserved across eukaryote evolution. In contrast to TOR complex 1 (TORC1), TORC2 kinase activity is not inhibited by the macrolide rapamycin. Here, we present the structure of Saccharomyces cerevisiae TORC2 determined by electron cryo-microscopy. TORC2 contains six subunits assembling into a 1.4 MDa rhombohedron. Tor2 and Lst8 form the common core of both TOR complexes. Avo3/Rictor is unique to TORC2, but interacts with the same HEAT repeats of Tor2 that are engaged by Kog1/Raptor in mammalian TORC1, explaining the mutual exclusivity of these two proteins. Density, which we conclude is Avo3, occludes the FKBP12-rapamycin-binding site of Tor2’s FRB domain rendering TORC2 rapamycin insensitive and recessing the kinase active site. Although mobile, Avo1/hSin1 further restricts access to the active site as its conserved-region-in-the-middle (CRIM) domain is positioned along an edge of the TORC2 active-site-cleft, consistent with a role for CRIM in substrate recruitment.
North Atlantic variability and its links to European climate over the last 3000 years
Authors: Moffa-Sánchez Paola , Hall Ian R.
Published: November 2017

The subpolar North Atlantic is a key location for the Earth’s climate system. In the Labrador Sea, intense winter air–sea heat exchange drives the formation of deep waters and the surface circulation of warm waters around the subpolar gyre. This process therefore has the ability to modulate the oceanic northward heat transport. Recent studies reveal decadal variability in the formation of Labrador Sea Water. Yet, crucially, its longer-term history and links with European climate remain limited. Here we present new decadally resolved marine proxy reconstructions, which suggest weakened Labrador Sea Water formation and gyre strength with similar timing to the centennial cold periods recorded in terrestrial climate archives and historical records over the last 3000 years. These new data support that subpolar North Atlantic circulation changes, likely forced by increased southward flow of Arctic waters, contributed to modulating the climate of Europe with important societal impacts as revealed in European history.
Scallop genome reveals molecular adaptations to semi-sessile life and neurotoxins
Authors: Li Yuli , Sun Xiaoqing , Hu Xiaoli , Xun Xiaogang , Zhang Jinbo , Guo Ximing , Jiao Wenqian , Zhang Lingling , Liu Weizhi , Wang Jing , Li Ji , Sun Yan , Miao Yan , Zhang Xiaokang , Cheng Taoran , Xu Guoliang , Fu Xiaoteng , Wang Yangfan , Yu Xinran , Huang Xiaoting , Lu Wei , Lv Jia , Mu Chuang , Wang Dawei , Li Xu , Xia Yu , Li Yajuan , Yang Zhihui , Wang Fengliang , Zhang Lu , Xing Qiang , Dou Huaiqian , Ning Xianhui , Dou Jinzhuang , Li Yangping , Kong Dexu , Liu Yaran , Jiang Zhi , Li Ruiqiang , Wang Shi , Bao Zhenmin
Published: November 2017

Bivalve molluscs are descendants of an early-Cambrian lineage superbly adapted to benthic filter feeding. Adaptations in form and behavior are well recognized, but the underlying molecular mechanisms are largely unknown. Here, we investigate the genome, various transcriptomes, and proteomes of the scallop Chlamys farreri, a semi-sessile bivalve with well-developed adductor muscle, sophisticated eyes, and remarkable neurotoxin resistance. The scallop’s large striated muscle is energy-dynamic but not fully differentiated from smooth muscle. Its eyes are supported by highly diverse, intronless opsins expanded by retroposition for broadened spectral sensitivity. Rapid byssal secretion is enabled by a specialized foot and multiple proteins including expanded tyrosinases. The scallop uses hepatopancreas to accumulate neurotoxins and kidney to transform to high-toxicity forms through expanded sulfotransferases, probably as deterrence against predation, while it achieves neurotoxin resistance through point mutations in sodium channels. These findings suggest that expansion and mutation of those genes may have profound effects on scallop’s phenotype and adaptation.
Ultrafast bridge planarization in donor-π-acceptor copolymers drives intramolecular charge transfer
Authors: Roy Palas , Jha Ajay , Yasarapudi Vineeth B. , Ram Thulasi , Puttaraju Boregowda , Patil Satish , Dasgupta Jyotishman
Published: November 2017

Donor-π-acceptor conjugated polymers form the material basis for high power conversion efficiencies in organic solar cells. Large dipole moment change upon photoexcitation via intramolecular charge transfer in donor-π-acceptor backbone is conjectured to facilitate efficient charge-carrier generation. However, the primary structural changes that drive ultrafast charge transfer step have remained elusive thereby limiting a rational structure-function correlation for such copolymers. Here we use structure-sensitive femtosecond stimulated Raman spectroscopy to demonstrate that π-bridge torsion forms the primary reaction coordinate for intramolecular charge transfer in donor-π-acceptor copolymers. Resonance-selective Raman snapshots of exciton relaxation reveal rich vibrational dynamics of the bridge modes associated with backbone planarization within 400 fs, leading to hot intramolecular charge transfer state formation while subsequent cooling dynamics of backbone-centric modes probe the charge transfer relaxation. Our work establishes a phenomenological gating role of bridge torsions in determining the fundamental timescale and energy of photogenerated carriers, and therefore opens up dynamics-based guidelines for fabricating energy-efficient organic photovoltaics.
The Aegilops tauschii genome reveals multiple impacts of transposons
Authors: Zhao Guangyao , Zou Cheng , Li Kui , Wang Kai , Li Tianbao , Gao Lifeng , Zhang Xiaoxia , Wang Hongjin , Yang Zujun , Liu Xu , Jiang Wenkai , Mao Long , Kong Xiuying , Jiao Yuannian , Jia Jizeng
Published: November 2017

Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time.
Aberrant perfusion and its connectivity within default mode network of first-episode drug-naïve schizophrenia patients and their unaffected first-degree relatives
Authors: Cui Long-Biao , Wang Liu-Xian , Tian Ping , Wang Hua-Ning , Cai Min , Guo Fan , Li Chen , Wu Yu-Jing , Qiao Peng-Gang , Xu Zi-Liang , Liu Lin , He Hong , Wu Wen-Jun , Xi Yi-Bin , Yin Hong
Published: November 2017

Neural substrates behind schizophrenia (SZ) and its heritability mediated by brain function are largely unknown. Cerebral blood flow (CBF), as a biomarker of activation in the brain, reflects the neuronal metabolism, and is promisingly used to detect cerebral alteration thereby shedding light on the features of individuals at high genetic risk. We performed a cross-sectional functional magnetic resonance imaging (MRI) study enrolling 45 first-episode drug-naïve patients with SZ, 32 unaffected first-degree relatives of these patients, and 51 healthy controls (HCs). We examined CBF, CBF connectivity, and CBF topological properties. SZ patients showed increased CBF in the left medial superior frontal gyrus and right precuneus compared with HCs, and decreased CBF in the left middle temporal gyrus compared with their relatives. Furthermore, unaffected relatives revealed higher level of CBF pronounced in regions within default mode network (DMN). Both SZ patients and their relatives exhibited dysconnectivity patterns. Notably, as for the network properties, unaffected relatives were with an intermediate level between SZ patients and HCs in the local efficiency and global efficiency. Our findings demonstrate the aberrant CBF of areas within DMN and the CBF connectivity pattern might be a familial feature in the brain of first-episode SZ patients and their relatives.
Systems analysis of latent HIV reversal reveals altered stress kinase signaling and increased cell death in infected T cells
Authors: Fong Linda E. , Sulistijo Endah S. , Miller-Jensen Kathryn
Published: November 2017

Viral latency remains the most significant obstacle to HIV eradication. Clinical strategies aim to purge the latent CD4+ T cell reservoir by activating viral expression to induce death, but are undercut by the inability to target latently infected cells. Here we explored the acute signaling response of latent HIV-infected CD4+ T cells to identify dynamic phosphorylation signatures that could be targeted for therapy. Stimulation with CD3/CD28, PMA/ionomycin, or latency reversing agents prostratin and SAHA, yielded increased phosphorylation of IκBα, ERK, p38, and JNK in HIV-infected cells across two in vitro latency models. Both latent infection and viral protein expression contributed to changes in perturbation-induced signaling. Data-driven statistical models calculated from the phosphorylation signatures successfully classified infected and uninfected cells and further identified signals that were functionally important for regulating cell death. Specifically, the stress kinase pathways p38 and JNK were modified in latently infected cells, and activation of p38 and JNK signaling by anisomycin resulted in increased cell death independent of HIV reactivation. Our findings suggest that altered phosphorylation signatures in infected T cells provide a novel strategy to more selectively target the latent reservoir to enhance eradication efforts.
Chemokines protect vascular smooth muscle cells from cell death induced by cyclic mechanical stretch
Authors: Zhao Jing , Nishimura Yuhei , Kimura Akihiko , Ozawa Kentaro , Kondo Toshikazu , Tanaka Toshio , Yoshizumi Masanori
Published: November 2017

The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs) in the vessel wall to cyclic mechanical stretch (CMS), which evokes VSMC proliferation, cell death, phenotypic switching, and migration, leading to vascular remodeling. These responses have been observed in many cardiovascular diseases; however, the underlying mechanisms remain unclear. We have revealed that CMS of rat aortic smooth muscle cells (RASMCs) causes JNK- and p38-dependent cell death and that a calcium channel blocker and angiotensin II receptor antagonist decreased the phosphorylation of JNK and p38 and subsequently decreased cell death by CMS. In the present study, we showed that the expression of Cxcl1 and Cx3cl1 was induced by CMS in a JNK-dependent manner. The expression of Cxcl1 was also induced in VSMCs by hypertension produced by abdominal aortic constriction (AAC). In addition, antagonists against the receptors for CXCL1 and CX3CL1 increased cell death, indicating that CXCL1 and CX3CL1 protect RASMCs from CMS-induced cell death. We also revealed that STAT1 is activated in RASMCs subjected to CMS. Taken together, these results indicate that CMS of VSMCs induces inflammation-related gene expression, including that of CXCL1 and CX3CL1, which may play important roles in the stress response against CMS caused by hypertension.
Identification of the Binding Sites on Rab5 and p110beta Phosphatidylinositol 3-kinase
Authors: Whitecross Dielle E. , Anderson Deborah H.
Published: November 2017

Rab5 is a small monomeric GTPase that mediates protein trafficking during endocytosis. Inactivation of Rab5 by GTP hydrolysis causes a conformational change that masks binding sites on its “switch regions” from downstream effectors. The p85 subunit of phosphatidylinositol 3-kinase (PI3K) is a GTPase activating protein (GAP) towards Rab5. Whereas p85 can bind with both Rab5-GTP and Rab5-GDP, the PI3K catalytic subunit p110β binds only Rab5-GTP, suggesting it interacts with the switch regions. Thus, the GAP functions of the catalytic arginine finger (from p85) and switch region stabilization (from p110β) may be provided by both proteins, acting together. To identify the Rab5 residues involved in binding p110β, residues in the Rab5 switch regions were mutated. A stabilized recombinant p110 protein, where the p85-iSH2 domain was fused to p110 (alpha or beta) was used in binding experiments. Eleven Rab5 mutants, including E80R and H83E, showed reduced p110β binding. The Rab5 binding site on p110β was also resolved through mutation of p110β in its Ras binding domain, and includes residues I234, E238 and Y244. This is a second region within p110β important for Rab5 binding. The Rab5-GTP:p110β interaction may be further elucidated through the characterization of these non-binding mutants in cells.
Larval Dispersal of Spodoptera frugiperda Strains on Bt Cotton: A Model for Understanding Resistance Evolution and Consequences for its Management
Authors: Malaquias José B. , Godoy Wesley A. C. , Garcia Adriano G. , Ramalho Francisco de S. , Omoto Celso
Published: November 2017

High dispersal of Lepidoptera larvae between non-Bt and Bt cotton plants can favour the evolution of insect resistance; however, information on host acceptance of neonates in tropical transgenic crops is scarce. Therefore, the purposes of this study were as follows: (i) to investigate the feeding behaviour of susceptible and Cry1F-resistant strains ofSpodoptera frugiperda(J.E. Smith) on Bt and non-Bt cotton (Gossypium hirsutumL.) varieties and (ii) to understand the possible effects of cotton field contamination on the dispersal and infestation capacity ofS.frugiperdalarvae by using an individual-based model. The main results of this paper are as follows: (1) the highest post-feeding larval dispersal of the Cry1F-resistant strain occurred at an exposure time of 18–24 h; (2) via video tracking assays, we found that the least distance moved was by larvae resistant to Cry1F on non-Bt cotton; and (3) the model indicated differences in mobility capacity between Bt and non-Bt cotton. We conclude that resistant neonates exhibit sedentary behaviour. Our report represents the first findings concerning the fitness cost of larval behaviour traits ofS.frugiperdaassociated with Cry1F resistance in Brazilian populations.
Publisher Correction: Novel detection of post-translational modifications in human monocyte-derived dendritic cells after chronic alcohol exposure: Role of inflammation regulator H4K12ac
Authors: Parira Tiyash , Figueroa Gloria , Laverde Alejandra , Casteleiro Gianna , Gomez Hernandez Mario E. , Fernandez-Lima Francisco , Agudelo Marisela
Published: November 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
Prognostic Value of Long Non-Coding RNA HULC and MALAT1 Following the Curative Resection of Hepatocellular Carcinoma
Authors: Sonohara Fuminori , Inokawa Yoshikuni , Hayashi Masamichi , Yamada Suguru , Sugimoto Hiroyuki , Fujii Tsutomu , Kodera Yasuhiro , Nomoto Shuji
Published: November 2017

Long non-coding RNAs (lncRNAs) were shown to be the crucial regulators of the many diseases. In this study, the expressions of lncRNAs were investigated in resected 158 hepatocellular carcinomas (HCCs) to evaluate the effects of their expression levels on prognosis. The expression levels of HULC and MALAT1 were shown to be significantly higher in the normal background tissue of HCC than those in the normal liver tissue of metastatic liver tumor without hepatitis (HULC: fold change 14.9, P = 1.7e-06; MALAT1: fold change 17.5, P = 1.2e-06. The formation of capsule was shown to be correlated with the increased expression of HULC (P = 0.041), while the size of HCC under 2 cm was correlated with a decrease in MALAT1 expression (P = 0.019). The levels of serum alpha-fetoprotein above 20 ng/mL indicated a decreased expression of both HULC and MALAT1 (HULC: P = 0.017; MALAT1: P = 0.0036). The increase in the expression levels of MALAT1 in HCC tissues was significantly correlated with better overall survival (HULC: P = 0.099, MALAT1: P = 0.028). Thus, the expression of these lncRNAs in HCC potentially correlates with the HCC malignancy and they represent potential prognostic biomarkers of the resected HCC.
Biofunctional analysis of Vitellogenin and Vitellogenin receptor in citrus red mites, Panonychus citri by RNA interference
Authors: Ali Muhammad Waqar , Zhang Zhen-yu , Xia Shuang , Zhang Hongyu
Published: November 2017

Panonychus citri is one of the most damaging pests of horticultural crops. Conventional control of this pest population through pesticides has led to the enhanced pest resistance. Management of P. citri population through RNAi, is still largely unknown. In oviparous organisms, fabrication and development of yolk protein play a vital role in the reproduction. Vitellin (Vn) is the source of eggs storage that helps in proper functioning of Vitellogenin (Vg) and Vitellogenin receptor (VgR). VgR is very compulsory protein for the development of Vg into oocytes. In the current study, Vg (PcVg) and VgR (PcVgR) genes were studied and their expressions at different developmental stages were quantified by RT-qPCR. Females treated with dsRNA of PcVg and PcVgR genes exhibited reduction in gene expression. Down regulation of target genes significantly effected oviposition and reduced the egg laying capacity up to 48% as compared to control (ds-egfp). Synergistic effect of target gene’s dsRNA was also accessed that reduced the egg laying up to 60.42%. Furthermore, combination of target dsRNA on deutonymph and protonymph also resulted in 67% and 70% reduction in eggs, respectively. Synergistic effect of dsRNA at 1000 ng/ul resulted in longer life span as compared to control treatments. This study suggests to develop a new strategy of P. citri population control by reducing its reproduction.
Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide
Authors: Lai Thung-S. , Lindberg Robert A. , Zhou Hua-Lin , Haroon Zishan A. , Dewhirst Mark W. , Hausladen Alfred , Juang Y.-L. , Stamler Jonathan S. , Greenberg Charles S.
Published: November 2017

Nitric oxide (NO) produced by endothelial cells in response to cytokines displays anti-inflammatory activity by preventing the adherence, migration and activation of neutrophils. The molecular mechanism by which NO operates at the blood-endothelium interface to exert anti-inflammatory properties is largely unknown. Here we show that on endothelial surfaces, NO is associated with the sulfhydryl-rich protein tissue transglutaminase (TG2), thereby endowing the membrane surfaces with anti-inflammatory properties. We find that tumor necrosis factor-α-stimulated neutrophil adherence is opposed by TG2 molecules that are bound to the endothelial surface. Alkylation of cysteine residues in TG2 or inhibition of endothelial NO synthesis renders the surface-bound TG2 inactive, whereas specific, high affinity binding of S-nitrosylated TG2 (SNO-TG2) to endothelial surfaces restores the anti-inflammatory properties of the endothelium, and reconstitutes the activity of endothelial-derived NO. We also show that SNO-TG2 is present in healthy tissues and that it forms on the membranes of shear-activated endothelial cells. Thus, the anti-inflammatory mechanism that prevents neutrophils from adhering to endothelial cells is identified with TG2 S-nitrosylation at the endothelial cell-blood interface.
Plasmonic enhanced low-threshold random lasing from dye-doped nematic liquid crystals with TiN nanoparticles in capillary tubes
Authors: Wan Yuan , An Yashuai , Deng Luogen
Published: November 2017

We report a plasmonic enhanced low-threshold random lasing from dye-doped nematic liquid crystals with titanium nitride (TiN) nanoparticles (NPDDNLC) in capillary tubes. The NPDDNLC sample yields a coherent random laser with about 0.3 nm in the full width at half maximum (FWHM). We find the laser threshold is decreased by introducing the TiN NPs into the dye-doped nematic liquid crystal sample. The laser threshold decreases with increasing the number density of TiN nanoparticles from 5.613 × 1010/ml to 5.314 × 1011/ml. We suggest that the low-threshold random laser is caused by the cooperative effect of the recurrent multiple scattering and field enhancement in the vicinity of TiN nanoparticles. The localized electric field near the TiN nanoparticles enhances the energy absorption of the dye and strengthens the fluorescence amplification. Moreover, we provide a new parameter (the relative efficiency of the stimulated radiation photons) to quantify the quality of the random laser, and we give expressions for the wavelength, mode, and whole emission spectrum. Finally, we find the emission spectrum depends strongly on the emission angle and we discuss the reasons. These findings provide a simple and efficient way for the realization of low-threshold random lasers with low cost.
Body representation disturbances in visual perception and affordance perception persist in eating disorder patients after completing treatment
Authors: Engel Manja M. , Keizer Anouk
Published: November 2017

Body image disturbances (BID) are a key feature of eating disorders (ED). Clinical experience shows that BID exists in patients who Completed their Eating Disorder Treatment (CEDT), however studies concerning BID in CEDT patients are often limited to cognition and affect, measured by interviews and questionnaires. The current study is the first systematic study investigating the full scope of the mental body representation, including bodily attitudes, visual perception of body size, tactile perception, and affordance perception in CEDT patients. ED patients (N = 22), CEDT patients (N = 39) and healthy controls (HC; N = 30) were compared on BID tasks including the Body Attitude Test (BAT), Visual Size Estimation (VSE), Tactile Estimation Task (TET), and Hoop Task (HT). Results on the BAT show higher scores for ED patients compared to CEDT patients and HC but no difference between CEDT patients and HC. Both ED and CEDT patients show larger overestimations on the VSE and HT compared to HC, where ED patients show the largest overestimations. No group differences were found on the TET. The results indicate the existence of disturbances in visual perception and affordance perception in CEDT patients. Research focussing on more effective treatments for ED addressing multiple (sensory) modalities is advised.
Ischemic Postconditioning Protects Against Intestinal Ischemia/Reperfusion Injury via the HIF-1α/miR-21 Axis
Authors: Jia Zhongzhi , Lian Weishuai , Shi Haifeng , Cao Chuanwu , Han Shilong , Wang Kai , Li Maoquan , Zhang Xiaoping
Published: November 2017

Intestinal ischemia/reperfusion (I/R) can lead to tissue damage associated with inflammation and mucosal apoptosis. Ischemic postconditioning (IPostC), a series of repeated, brief, intermittent periods of ischemia and reperfusion, has beneficial effects against I/R-induced injury in the heart and intestine, although the underlying mechanisms for these effects remain unclear. We evaluated the involvement of microRNA-21 (miR-21) in the protective effects of IPostC in a rat model of I/R induced by superior mesenteric artery occlusion and reopening. IPostC decreased I/R injury and suppressed apoptosis in the intestinal tissues concomitant with the induction of hypoxia inducible factor 1 alpha (HIF-1α) and the upregulation of miR-21. In vitro experiments in the intestinal epithelial cell line IEC-6 showed that hypoxia induced miR-21 and this effect was abolished by silencing HIF1-α, confirming the induction of miR-21 by HIF1-α, HIF1-α or miR-21 inhibition exacerbated I/R induced apoptosis, and programmed cell death 4 (PDCD4) and Fas-L was involved in miR-21 mediated anti-apoptotic effects on intestinal epithelial cells. Knockdown of miR-21 or inhibition of HIF1-α abolished the IPostC-mediated attenuation of intestinal injury and apoptosis and the downregulation of PDCD4 and Fas-L. A potential mechanism underlying the protective effect of IPostC may therefore involve the induction of miR-21 by HIF1-α and the attenuation of apoptosis via the downregulation of PDCD4 and Fas-L.
Second messenger analogues highlight unexpected substrate sensitivity of CD38: total synthesis of the hybrid “L-cyclic inosine 5′-diphosphate ribose”
Authors: Watt Joanna M. , Graeff Richard , Thomas Mark P. , Potter Barry V. L.
Published: November 2017

The multifunctional, transmembrane glycoprotein human CD38 catalyses the synthesis of three key Ca2+-mobilising messengers, including cyclic adenosine 5′-diphosphate ribose (cADPR), and CD38 knockout studies have revealed the relevance of the related signalling pathways to disease. To generate inhibitors of CD38 by total synthesis, analogues based on the cyclic inosine 5′-diphosphate ribose (cIDPR) template were synthesised. In the first example of a sugar hybrid cIDPR analogue, “L-cIDPR”, the natural “northern” N1-linked D-ribose of cADPR was replaced by L-ribose. L-cIDPR is surprisingly still hydrolysed by CD38, whereas 8-Br-L-cIDPR is not cleaved, even at high enzyme concentrations. Thus, the inhibitory activity of L-cIDPR analogues appears to depend upon substitution of the base at C-8; 8-Br-L-cIDPR and 8-NH2-L-cIDPR inhibit CD38-mediated cADPR hydrolysis (IC50 7 μM and 21 µM respectively) with 8-Br-L-cIDPR over 20-fold more potent than 8-Br-cIDPR. In contrast, L-cIDPR displays a comparative 75-fold reduction in activity, but is only ca 2-fold less potent than cIDPR itself. Molecular modelling was used to explore the interaction of the CD38 catalytic residue Glu-226 with the “northern” ribose. We propose that Glu226 still acts as the catalytic residue even for an L-sugar substrate. 8-Br-L-cIDPR potentially binds non-productively in an upside-down fashion. Results highlight the key role of the “northern” ribose in the interaction of cADPR with CD38.
Age-dependent and regional heterogeneity in the long-chain base of A-series gangliosides observed in the rat brain using MALDI Imaging
Authors: Caughlin Sarah , Maheshwari Shikhar , Weishaupt Nina , Yeung Ken K-C , Cechetto David Floyd , Whitehead Shawn Narain
Published: November 2017

Alterations in the long chain base of the sphingosine moiety of gangliosides have been shown to play a role in neurodevelopment and neurodegeneration. Indeed, the accumulation of d20:1 sphingosine has been referred to as a metabolic marker of aging in the brain, however, this remains to be shown in simple gangliosides GM2 and GM3. In this study, Matrix-assisted laser desorption/ionization Imaging Mass Spectrometry (MALDI IMS) was used to examine the neuroanatomical distribution of A-series gangliosides with either 18 or 20 carbon sphingosine chains (d18:1 or d20:1) in Fisher 344 rats across the lifespan. The ratio of d20:1/d18:1 species was determined across 11 regions of interest in the brain. Interestingly, a decrease in the d20:1/d18:1 ratio for GM2 and GM3 was observed during early development with the exception of the peri-ventricular corpus callosum, where an age-dependent increase was observed for ganglioside GM3. An age-dependent increase in d20:1 species was confirmed for complex gangliosides GM1 and GD1 with the most significant increase during early development and a high degree of anatomical heterogeneity during aging. The unique neuroanatomically-specific responses of d20:1 ganglioside abundance may lead to a better understanding of regional vulnerability to damage in the aging brain.
PDGFR Signaling Mediates Hyperproliferation and Fibrotic Responses of Subsynovial Connective Tissue Cells in Idiopathic Carpal Tunnel Syndrome
Authors: Saito Yuki , Chikenji Takako , Ozasa Yasuhiro , Fujimiya Mineko , Yamashita Toshihiko , Gingery Anne , Iba Kousuke
Published: November 2017

Fibrosis of the subsynovial connective tissue (SSCT) is a pathognomonic change in carpal tunnel syndrome (CTS). Identification of molecular targets and anti-fibrotic therapies could provide new treatment strategies for CTS. The contribution of SSCT cells to fibrosis and the signaling pathways that initiate and aggravate fibrosis in CTS remain unknown. Here we report that platelet-derived growth factor receptor alpha (PDGFRα) positive ( + ) cells accumulate in CTS SSCT and that the presence of fibrotic growth factor, PDGF-AA, results in increased proliferation of PDGFRα+ cells via PI3K/Akt signaling pathway. Although PI3K inhibition decreased proliferation, there was no change in fibrosis-related gene expression. Indeed, protein levels of fibrosis signaling mediator TGF-β remained the same and the second messenger, Smad2/3, accumulated in the nucleus. In contrast AMP-activated protein kinase (AMPK) activation, which can be induced with metformin and AICAR inhibited proliferation, TGF-β expression, and altered cell morphology in SSCT cells. Further we show that AMPK activation by metformin reduced collagen III levels and the ratio of Collagen I to Collagen III. Both AICAR and metformin reduced F-actin and significantly reduced the fiber cross alignment. Our results suggest that PDGFRa signaling may be an important fibrosis target and that activators of AMPK, may be an important therapeutic approach for treating CTS.
Quantitative analysis of motor evoked potentials in the neonatal lamb
Authors: Joyeux Luc , Deprez Marjolijn , Khatoun Ahmad , Van Kuyck Kris , Pelsmaekers Kelly , Engels Alexander C. , Wang Hongmei , Monteiro Carvalho Mori da Cunha Marina Gabriela , De Vleeschauwer Stephanie , Mc Laughlin Myles , Deprest Jan
Published: November 2017

Evoking motor potentials are an objective assessment method for neuromotor function, yet this was to our knowledge never done in neonatal lambs. There is neither a method for standardized quantification of motor evoked potentials (MEPs). We first aimed to evaluate the feasibility of MEP recording in neonatal lambs and test its validity. Second we aimed to develop an algorithm for its quantification and test its reliability since manual input is required. We recorded myogenic MEPs after transcranial motor cortex stimulation in 6 lambs aged 1–2 days. MEPs were also measured in one lamb undergoing Neuro-Muscular Blockade (NMB) and another undergoing lumbar spinal cord (SC) transection, both serving as controls. We computed 5 parameters using a custom-made algorithm: motor threshold, latency, area-under-the-curve, peak-to-peak amplitude and duration. Intra- and inter-observer reliability was analyzed. MEPs could be easily recorded, disappearing after NMB and SC transection. The algorithm allowed for analysis, hence physiologic readings of the parameters in all 4 limbs of all lambs were obtained. Our method was shown to have high intra- and inter-observer ( ≥70%) reliability for latency, area-under-the-curve and peak-to-peak amplitude. These results suggest that standardized MEP recording and analysis in neonatal lambs is feasible, and can reliably assess neuromotor function.
Solar energy converters based on multi-junction photoemission solar cells
Authors: Tereshchenko O. E. , Golyashov V. A. , Rodionov A. A. , Chistokhin I. B. , Kislykh N. V. , Mironov A. V. , Aksenov V. V.
Published: November 2017

Multi-junction solar cells with multiple p–n junctions made of different semiconductor materials have multiple bandgaps that allow reducing the relaxation energy loss and substantially increase the power-conversion efficiency. The choice of materials for each sub-cell is very limited due to the difficulties in extracting the current between the layers caused by the requirements for lattice- and current-matching. We propose a new vacuum multi-junction solar cell with multiple p-n junctions separated by vacuum gaps that allow using different semiconductor materials as cathode and anode, both activated to the state of effective negative electron affinity (NEA). In this work, the compact proximity focused vacuum tube with the GaAs(Cs,O) photocathode and AlGaAs/GaAs-(Cs,O) anode with GaAs quantum wells (QWs) is used as a prototype of a vacuum single-junction solar cell. The photodiode with the p-AlGaAs/GaAs anode showed the spectral power-conversion efficiency of about 1% at V
bias
 = 0 in transmission and reflection modes, while, at V
bias
 = 0.5 V, the efficiency increased up to 10%. In terms of energy conservation, we found the condition at which the energy cathode-to-anode transition was close to 1. Considering only the energy conservation part, the NEA-cell power-conversion efficiency can rich a quantum yield value which is measured up to more than 50%.
Non-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI
Authors: Zun Zungho , Zaharchuk Greg , Andescavage Nickie N. , Donofrio Mary T. , Limperopoulos Catherine
Published: November 2017

The placenta is a vital organ for fetal growth and development during pregnancy. Congenital heart disease (CHD) is a leading cause of morbidity and mortality in newborns. Despite the parallel development of the placenta and fetal heart early in pregnancy, very few studies suggested an association between placental dysfunction and fetal CHD. In this study, we report placental perfusion of healthy pregnancies and pregnancies complicated by fetal CHD measured using advanced fetal MRI techniques. We studied forty-eight pregnant women (31 healthy volunteers and 17 with fetal CHD) that underwent fetal MRI during their second or third trimester of pregnancy. Placental perfusion imaging was performed using velocity-selective arterial spin labeling (VSASL) and 3D image acquisition with whole-placenta coverage. In pregnancies with fetal CHD, global placental perfusion significantly decreased and regional variation of placental perfusion significantly increased with advancing gestational age; however, no such correlation was found in healthy pregnancies. Also, global placental perfusion was significantly higher in fetal CHD versus controls, in the lateral side-lying patient position versus supine, and in the posterior placental position versus anterior placental position. This study reports for the first time non-invasive whole-placenta perfusion imaging in utero. These data suggest that placental VSASL may serve as a potential biomarker of placental dysfunction in fetuses diagnosed with CHD.
Lipoprotein-associated phospholipase A2 and oxidized low-density lipoprotein in young patients with acute coronary syndrome in China
Authors: Huang Yuli , Wu Yu , Yang You , Li Wensheng , Lu Jianhua , Hu Yunzhao
Published: November 2017

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered to be a risk factor for acute coronary syndrome (ACS), but this remains controversial. This study investigated the role of Lp-PLA2 in young Chinese patients with ACS. 228 young patients (aged ≤55 years) with ACS and 237 age-matched controls were included. Lp-PLA2 and oxidized low-density lipoprotein (ox-LDL) levels were measured by sandwich enzyme-linked immunosorbent assay. Lp-PLA2 levels were significantly correlated with smoking, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ox-LDL levels (all P < 0.05). Multivariate logistic regression analysis showed that male sex (OR = 3.25, 95%CI = 1.26–8.38), smoking (OR = 3.50, 95%CI = 1.75–7.0), triglyceride (OR = 1.76, 95%CI = 1.08–2.87), high sensitivity C-reactive protein (hs-CRP) (OR = 2.11, 95%CI = 1.14–3.90) and ox-LDL (OR = 2.98, 95%CI = 1.72–5.1) were independently associated with ACS risk in young patients. Lp-PLA2 was associated with risk of ACS in young patients when adjusted for traditional risk factors, including age, sex, diabetes, hypertension, smoking, TC, LDL-C, triglyceride and hs-CRP (OR = 1.98, 95%CI = 1.10–3.56). When further adjusted for ox-LDL levels, the association between Lp-PLA2 and ACS became insignificant (OR = 1.69, 95%CI = 0.90–3.17). Lp-PLA2 was a marker of oxidative stress and inflammation, rather than an independent risk factor for ACS in young Chinese patients.