bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction and inhibition of the pan-nuclear gamma-H2AX response in resting human peripheral blood lymphocytes after X-ray irradiation
Authors: Ding D , Zhang Y , Wang J , Zhang X , Gao Y , Yin L , Li Q , Li J , Chen H
Published: March 2016

Human peripheral blood lymphocytes (HPBLs) are one of the most sensitive cells to ionizing radiation (IR) in the human body, and IR-induced DNA damage and functional impairment of HPBLs are the adverse consequences of IR accidents and major side effects of radiotherapy. Phosphorylated H2AX (γH2AX) is a sensitive marker for DNA double-strand breaks, but the role and regulation of the pan-nuclear γH2AX response in HPBLs after IR remain unclear. We herein demonstrated that the pan-nuclear γH2AX signals were increased in a time- and dose-dependent manner, colocalized with >94% of TUNEL apoptotic staining, and displayed a typical apoptotic pattern in resting HPBLs after low LET X-ray IR. In addition, the X-irradiation-induced pan-nuclear p-ATM and p-DNA-PKcs responses also occurred in resting HPBLs, and were colocalized with 92–95% of TUNEL staining and 97–98% of the pan-nuclear γH2AX signals, respectively, with a maximum at 6 h post irradiation, but disappeared at 24 h post irradiation. Moreover, ATM/DNA-PKcs inhibitor KU55933, p53 inhibitor PFT-μ and pan-caspase inhibitor ZVAD-fmk significantly decreased X-irradiation-induced pan-nuclear γH2AX signals and TUNEL staining, protected HPBLs from apoptosis, but decreased the proliferative response to mitogen in X-irradiated HPBLs. Notably, whereas both KU55933 and PFT-μ increased the IR-induced chromosome breaks and mis-repair events through inhibiting the formation of p-ATM, p-DNA-PKcs and γH2AX foci in X-irradiated HPBLs, the ZVAD-fmk did not increase the IR-induced chromosomal instability. Taken together, our data indicate that pan-nuclear γH2AX response represents an apoptotic signal that is triggered by the transient pan-nuclear ATM and DNA-PKcs activation, and mediated by p53 and pan-caspases in X-irradiated HPBLs, and that caspase inhibitors are better than ATM/DNA-PKcs inhibitors and p53 inhibitors to block pan-nuclear γH2AX response/apoptosis and protect HPBLs from IR.
Li(V0.5Ti0.5)S2 as a 1 V lithium intercalation electrode
Authors: Clark Steve J. , Wang Da , Armstrong A. Robert , Bruce Peter G.
Published: March 2016

Graphite, the dominant anode in rechargeable lithium batteries, operates at ∼0.1 V versus Li+/Li and can result in lithium plating on the graphite surface, raising safety concerns. Titanates, for example, Li4Ti5O12, intercalate lithium at∼1.6 V versus Li+/Li, avoiding problematic lithium plating at the expense of reduced cell voltage. There is interest in 1 V anodes, as this voltage is sufficiently high to avoid lithium plating while not significantly reducing cell potential. The sulfides, LiVS2 and LiTiS2, have been investigated as possible 1 V intercalation electrodes but suffer from capacity fading, large 1st cycle irreversible capacity or polarization. Here we report that the 50/50 solid solution, Li1+x(V0.5Ti0.5)S2, delivers a reversible capacity to store charge of 220 mAhg−1 (at 0.9 V), 99% of theoretical, at a rate of C/2, retaining 205 mAhg−1 at C-rate (92% of theoretical). Rate capability is excellent with 200 mAhg−1 at 3C. C-rate is discharge in 1 h. Polarization is low, 100 mV at C/2. To the best of our knowledge, the properties/performances of Li(V0.5Ti0.5)S2 exceed all previous 1 V electrodes.
miR-34 activity is modulated through 5′-end phosphorylation in response to DNA damage
Authors: Salzman David W. , Nakamura Kotoka , Nallur Sunitha , Dookwah Michelle T. , Metheetrairut Chanatip , Slack Frank J. , Weidhaas Joanne B.
Published: March 2016

MicroRNA (miRNA) expression is tightly regulated by several mechanisms, including transcription and cleavage of the miRNA precursor RNAs, to generate a mature miRNA, which is thought to be directly correlated with activity. MiR-34 is a tumour-suppressor miRNA important in cell survival, that is transcriptionally upregulated by p53 in response to DNA damage. Here, we show for the first time that there is a pool of mature miR-34 in cells that lacks a 5′-phosphate and is inactive. Following exposure to a DNA-damaging stimulus, the inactive pool of miR-34 is rapidly activated through 5′-end phosphorylation in an ATM- and Clp1-dependent manner, enabling loading into Ago2. Importantly, this mechanism of miR-34 activation occurs faster than, and independently of, de novo p53-mediated transcription and processing. Our study reveals a novel mechanism of rapid miRNA activation in response to environmental stimuli occurring at the mature miRNA level.
Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans
Authors: Houtepen Lotte C. , Vinkers Christiaan H. , Carrillo-Roa Tania , Hiemstra Marieke , van Lier Pol A. , Meeus Wim , Branje Susan , Heim Christine M. , Nemeroff Charles B. , Mill Jonathan , Schalkwyk Leonard C. , Creyghton Menno P. , Kahn René S. , Joëls Marian , Binder Elisabeth B. , Boks Marco P. M.
Published: March 2016

DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 × 10−6). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability.
Ciliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation
Authors: Yuan Xue , Cao Jay , He Xiaoning , Serra Rosa , Qu Jun , Cao Xu , Yang Shuying
Published: March 2016

Intraflagellar transport proteins (IFT) are required for hedgehog (Hh) signalling transduction that is essential for bone development, however, how IFT proteins regulate Hh signalling in osteoblasts (OBs) remains unclear. Here we show that deletion of ciliary IFT80 in OB precursor cells (OPC) in mice results in growth retardation and markedly decreased bone mass with impaired OB differentiation. Loss of IFT80 blocks canonical Hh–Gli signalling via disrupting Smo ciliary localization, but elevates non-canonical Hh–Gαi–RhoA–stress fibre signalling by increasing Smo and Gαi binding. Inhibition of RhoA and ROCK activity partially restores osteogenic differentiation of IFT80-deficient OPCs by inhibiting non-canonical Hh–RhoA–Cofilin/MLC2 signalling. Cytochalasin D, an actin destabilizer, dramatically restores OB differentiation of IFT80-deficient OPCs by disrupting actin stress fibres and promoting cilia formation and Hh–Gli signalling. These findings reveal that IFT80 is required for OB differentiation by balancing between canonical Hh–Gli and non-canonical Hh–Gαi–RhoA pathways and highlight IFT80 as a therapeutic target for craniofacial and skeletal abnormalities.
Collaboration between primitive cell membranes and soluble catalysts
Authors: Adamala Katarzyna P. , Engelhart Aaron E. , Szostak Jack W.
Published: March 2016

One widely held model of early life suggests primitive cells consisted of simple RNA-based catalysts within lipid compartments. One possible selective advantage conferred by an encapsulated catalyst is stabilization of the compartment, resulting from catalyst-promoted synthesis of key membrane components. Here we show model protocell vesicles containing an encapsulated enzyme that promotes the synthesis of simple fatty acid derivatives become stabilized to Mg2+, which is required for ribozyme activity and RNA synthesis. Thus, protocells capable of such catalytic transformations would have enjoyed a selective advantage over other protocells in high Mg2+ environments. The synthetic transformation requires both the catalyst and vesicles that solubilize the water-insoluble precursor lipid. We suggest that similar modified lipids could have played a key role in early life, and that primitive lipid membranes and encapsulated catalysts, such as ribozymes, may have acted in conjunction with each other, enabling otherwise-impossible chemical transformations within primordial cells.
Correction: Corrigendum: An interactive web-based application for Comprehensive Analysis of RNAi-screen Data
Authors: Dutta Bhaskar , Azhir Alaleh , Merino Louis-Henri , Guo Yongjian , Revanur Swetha , Madhamshettiwar Piyush B. , Germain Ronald N. , Smith Jennifer A. , Simpson Kaylene J. , Martin Scott E. , Buehler Eugen , Fraser Iain D. C.
Published: March 2016

Nature Communications 7: Article number: 10578 (2016); Published 23 February 2016; Updated 21 March 2016 The original version of this article contained an error in the spelling of the author Eugen Buehler, which was incorrectly given as Eugen Beuhler. This has now been corrected in both the PDF and HTML versions of the article.
A monoclonal antibody targeting ErbB2 domain III inhibits ErbB2 signaling and suppresses the growth of ErbB2-overexpressing breast tumors
Authors: Meng Y , Zheng L , Yang Y , Wang H , Dong J , Wang C , Zhang Y , Yu X , Wang L , Xia T , Zhang D , Guo Y , Li B
Published: March 2016

The anti-ErbB2 antibodies trastuzumab and pertuzumab in combination have recently been approved for the treatment of patients with ErbB2-positive metastatic breast cancer. Pertuzumab, which binds to ErbB2 near the center of domain II, and trastuzumab, which binds to the juxtamembrane region of ErbB2 domain IV, directly interfere with domain II- and domain IV-mediated heterodimerization contacts, respectively. In this study, we report a novel anti-ErbB2 antibody, 3E10, which binds to an epitope in domain III that appears to be located opposite to the dimerization interfaces in domain II and domain IV of ErbB2. Our data show that the 3E10 antibody inhibits ErbB2 heterodimerization via a mechanism that strikingly differs from trastuzumab and pertuzumab. It could be speculated that the 3E10 antibody may affect ErbB2 heterodimerization by causing major conformational changes of ErbB2. Furthermore, 3E10 provides synergistic inhibition of ErbB2 heterodimerization and signaling in combination with either trastuzumab or pertuzumab. The combination of these three anti-ErbB2 antibodies that have complementary mechanisms of action appears to be an extremely potent ErbB2 heterodimerization blocker. Compared with trastuzumab plus pertuzumab, the combination of trastuzumab, pertuzumab and 3E10 provides a more potent blockade of ErbB2 signaling. Consistent with this, trastuzumab plus pertuzumab plus 3E10 results in greater in vitro and in vivo antitumor activity in ErbB2-overexpressing breast tumor models, suggesting its potential use for treating ErbB2-overexpressing breast cancer.
Periodic forces trigger knot untying during translocation of knotted proteins
Authors: Szymczak Piotr
Published: March 2016

Proteins need to be unfolded when translocated through the pores in mitochondrial and other cellular membranes. Knotted proteins, however, might get stuck during this process, jamming the pore, since the diameter of the pore is smaller than the size of maximally tightened knot. The jamming probability dramatically increases as the magnitude of the driving force exceeds a critical value,Fc. In this numerical study, we show that for deep knotsFclies below the force range over which molecular import motors operate, which suggest that in these cases the knots will tighten and block the pores. Next, we show how such topological traps might be prevented by using a pulling protocol of a repetitive, on-off character. Such a repetitive pulling is biologically relevant, since the mitochondrial import motor, like other molecular motors transforms chemical energy into directed motions via nucleotide-hydrolysis-mediated conformational changes, which are cyclic in character.
Ungulate malaria parasites
Authors: Templeton Thomas J. , Asada Masahito , Jiratanh Montakan , Ishikawa Sohta A. , Tiawsirisup Sonthaya , Sivakumar Thillaiampalam , Namangala Boniface , Takeda Mika , Mohkaew Kingdao , Ngamjituea Supawan , Inoue Noboru , Sugimoto Chihiro , Inagaki Yuji , Suzuki Yasuhiko , Yokoyama Naoaki , Kaewthamasorn Morakot , Kaneko Osamu
Published: March 2016

Haemosporida parasites of even-toed ungulates are diverse and globally distributed, but since their discovery in 1913 their characterization has relied exclusively on microscopy-based descriptions. In order to bring molecular approaches to bear on the identity and evolutionary relationships of ungulate malaria parasites, we conducted Plasmodium cytb-specific nested PCR surveys using blood from water buffalo in Vietnam and Thailand, and goats in Zambia. We found that Plasmodium is readily detectable from water buffalo in these countries, indicating that buffalo Plasmodium is distributed in a wider region than India, which is the only area in which buffalo Plasmodium has been reported. Two types (I and II) of Plasmodium sequences were identified from water buffalo and a third type (III) was isolated from goat. Morphology of the parasite was confirmed in Giemsa-reagent stained blood smears for the Type I sample. Complete mitochondrial DNA sequences were isolated and used to infer a phylogeny in which ungulate malaria parasites form a monophyletic clade within the Haemosporida, and branch prior to the clade containing bird, lizard and other mammalian Plasmodium. Thus it is likely that host switching of Plasmodium from birds to mammals occurred multiple times, with a switch to ungulates independently from other mammalian Plasmodium.
Robust Room-Temperature Quantum Spin Hall Effect in Methyl-functionalized InBi honeycomb film
Authors: Li Sheng-shi , Ji Wei-xiao , Zhang Chang-wen , Hu Shu-jun , Li Ping , Wang Pei-ji , Zhang Bao-min , Cao Chong-long
Published: March 2016

Two-dimensional (2D) group-III-V honeycomb films have attracted significant interest for their potential application in fields of quantum computing and nanoelectronics. Searching for 2D III-V films with high structural stability and large-gap are crucial for the realizations of dissipationless transport edge states using quantum spin Hall (QSH) effect. Based on first-principles calculations, we predict that the methyl-functionalized InBi monolayer (InBiCH3) has no dynamic instability and hosts QSH state with a band gap as large as 0.29 eV, exhibiting an interesting electronic behavior viable for room-temperature applications. The topological characteristic is confirmed by s-pxy band inversion, topological invariant Z2 number and the time-reversal symmetry protected helical edge states. Noticeably, the QSH states are tunable and robust against the mechanical strain, electric field and different levels of methyl coverages. We also find that InBiCH3 supported on h-BN substrate maintains a nontrivial QSH state, which harbors the edge states lying within the band gap of substrate. These findings demonstrate that the methyl-functionalized III-V films may be a good QSH platform for device design and fabrication in spintronics.
A two-component system regulates gene expression of the type IX secretion component proteins via an ECF sigma factor
Authors: Kadowaki Tomoko , Yukitake Hideharu , Naito Mariko , Sato Keiko , Kikuchi Yuichiro , Kondo Yoshio , Shoji Mikio , Nakayama Koji
Published: March 2016

The periodontopathogen Porphyromonas gingivalis secretes potent pathogenic proteases, gingipains, via the type IX secretion system (T9SS). This system comprises at least 11 components; however, the regulatory mechanism of their expression has not yet been elucidated. Here, we found that the PorY (PGN_2001)-PorX (PGN_1019)-SigP (PGN_0274) cascade is involved in the regulation of T9SS. Surface plasmon resonance (SPR) analysis revealed a direct interaction between a recombinant PorY (rPorY) and a recombinant PorX (rPorX). rPorY autophosphorylated and transferred a phosphoryl group to rPorX in the presence of Mn2+. These results demonstrate that PorX and PorY act as a response regulator and a histidine kinase, respectively, of a two component system (TCS), although they are separately encoded on the chromosome. T9SS component-encoding genes were down-regulated in a mutant deficient in a putative extracytoplasmic function (ECF) sigma factor, PGN_0274 (SigP), similar to the porX mutant. Electrophoretic gel shift assays showed that rSigP bound to the putative promoter regions of T9SS component-encoding genes. The SigP protein was lacking in the porX mutant. Co-immunoprecipitation and SPR analysis revealed the direct interaction between SigP and PorX. Together, these results indicate that the PorXY TCS regulates T9SS-mediated protein secretion via the SigP ECF sigma factor.
Room-temperature local ferromagnetism and its nanoscale expansion in the ferromagnetic semiconductor Ge1–xFex
Authors: Wakabayashi Yuki K. , Sakamoto Shoya , Takeda Yuki-haru , Ishigami Keisuke , Takahashi Yukio , Saitoh Yuji , Yamagami Hiroshi , Fujimori Atsushi , Tanaka Masaaki , Ohya Shinobu
Published: March 2016

We investigate the local electronic structure and magnetic properties of the group-IV-based ferromagnetic semiconductor, Ge1−xFex (GeFe), using soft X-ray magnetic circular dichroism. Our results show that the doped Fe 3d electrons are strongly hybridized with the Ge 4p states, and have a large orbital magnetic moment relative to the spin magnetic moment; i.e., morb/mspin ≈ 0.1. We find that nanoscale local ferromagnetic regions, which are formed through ferromagnetic exchange interactions in the high-Fe-content regions of the GeFe films, exist even at room temperature, well above the Curie temperature of 20–100 K. We observe the intriguing nanoscale expansion of the local ferromagnetic regions with decreasing temperature, followed by a transition of the entire film into a ferromagnetic state at the Curie temperature.
In vivo imaging of prostate cancer using an anti-PSMA scFv fragment as a probe
Authors: Mazzocco Claire , Fracasso Giulio , Germain-Genevois Coralie , Dugot-Senant Nathalie , Figini Mariangela , Colombatti Marco , Grenier Nicolas , Couillaud Franck
Published: March 2016

We aimed to evaluate a fluorescent-labeled single chain variable fragment (scFv) of the anti-PSMA antibody as a specific probe for the detection of prostate cancer by in vivo fluorescence imaging. An orthotopic model of prostate cancer was generated by injecting LNCaP cells into the prostate lobe. ScFvD2B, a high affinity anti-PSMA antibody fragment, was labeled using a near-infrared fluorophore to generate a specific imaging probe (X770-scFvD2B). PSMA-unrelated scFv-X770 was used as a control. Probes were injected intravenously into mice with prostate tumors and fluorescence was monitored in vivo by fluorescence molecular tomography (FMT). In vitro assays showed that X770-scFvD2B specifically bound to PSMA and was internalized in PSMA-expressing LNCaP cells. After intravenous injection, X770-scFvD2B was detected in vivo by FMT in the prostate region. On excised prostates the scFv probe co-localized with the cancer cells and was found in PSMA-expressing cells. The PSMA-unrelated scFv used as a control did not label the prostate cancer cells. Our data demonstrate that scFvD2B is a high affinity contrast agent for in vivo detection of PSMA-expressing cells in the prostate. NIR-labeled scFvD2B could thus be further developed as a clinical probe for imaging-guided targeted biopsies.
Geometry, Electronic Structure, and Pseudo Jahn-Teller Effect in Tetrasilacyclobutadiene Analogues
Authors: Liu Yang , Wang Ya , Bersuker Isaac B.
Published: March 2016

We revealed the origin of the structural features of a series of tetrasilacyclobutadiene analogues based on a detailed study of their electronic structure and the pseudo Jahn-Teller effect (PJTE). Starting with the D4h symmetry of the Si4R4 system with a square four-membered silicon ring as a reference geometry, and employing ab initio calculations of energy profiles along lower-symmetry nuclear displacements in the ground and several excited states, we show that the ground-state boat-like and chair-like equilibrium configurations are produced by the PJT interaction with appropriate excited sates. For Si4F4 a full two-mode b1g−b2g adiabatic potential energy surface is calculated showing explicitly the way of transformation from the unstable D4h geometry to the two equilibrium C2h configurations via the D2h saddle point. The PJTE origin of these structural features is confirmed also by estimates of the vibronic coupling parameters. For Si4R4 with large substituents the origin of their structure is revealed by analyzing the PJT interaction between the frontier molecular orbitals. The preferred chair-like structures of Si4R4 analogues with amido substituents, and heavier germanium-containing systems Ge4R4 (potential precursors for semiconducting materials) are predicted.
Historical Records of Mercury Stable Isotopes in Sediments of Tibetan Lakes
Authors: Yin Runsheng , Feng Xinbin , Hurley James P. , Krabbenhoft David P. , Lepak Ryan F. , Kang Shichang , Yang Handong , Li Xiangdong
Published: March 2016

The Tibetan Plateau (TP), known as the “Third Pole”, is a critical zone for atmospheric mercury (Hg) deposition. Increasing anthropogenic activities in the globe leads to environmental changes, which may affect the loading, transport and deposition of Hg in the environment. However, the deposition history and geochemical cycling of Hg in the TP is still uncertain. Our records of Hg and Hg isotopes in sediment profiles of the two largest lakes in the TP, Lake Qinghai and Nam Co, show increased Hg influx since last century, with the maximum Hg influx enrichment ratios of 5.4 and 3.5 in Lake Qinghai and Nam Co, respectively. Shifts in negative δ 202Hg in Lake Qinghai (−4.55 to −3.15‰) and Nam Co (−5.04 to −2.16‰) indicate increased atmospheric Hg deposition through rainfall, vegetation and runoff of soils. Mass independent fractionation of both even-Hg (∆ 200Hg: +0.05 to +0.10‰) and odd-Hg (∆ 199Hg: +0.12 to +0.31‰) isotopes were observed. Positive Δ 200Hg suggest high proportion of precipitation-derived Hg in the TP, whereas the positive Δ 199Hg results from Hg(II) photo-reduction. Both lakes show increasing Δ 199Hg since the 1900 s and we conclude that with the decrease of ice duration, Hg(II) photo-reduction may have been accelerated in these TP lakes.
Deletion of Galectin-3 Enhances Xenobiotic Induced Murine Primary Biliary Cholangitis by Facilitating Apoptosis of BECs and Release of Autoantigens
Authors: Arsenijevic Aleksandar , Milovanovic Marija , Milovanovic Jelena , Stojanovic Bojana , Zdravkovic Natasa , Leung Patrick S.C. , Liu Fu-Tong , Gershwin M. Eric , Lukic Miodrag L.
Published: March 2016

Galectin-3 (Gal-3) is a carbohydrate binding lectin, with multiple roles in inflammatory diseases and autoimmunity including its antiapoptotic effect on epithelial cells. In particular, increased expression of Gal-3 in epithelial cells is protective from apoptosis. Based on the thesis that apoptosis of biliary epithelial cells (BECs) is critical to the pathogenesis of Primary Biliary Cholangitis (PBC), we have analyzed the role of Gal-3 in the murine model of autoimmune cholangitis. We took advantage of Gal-3 knockout mice and immunized them with a mimotope of the major mitochondrial autoantigen of PBC, 2-octynoic acid (2-OA) coupled to BSA (2OA-BSA) and evaluated the natural history of subsequent disease, compared to control wild-type mice, by measuring levels of antibodies to PDC-E2, immunohistology of liver and expression of Gal-3. We report herein that deletion of Gal-3 significantly exacerbates autoimmune cholangitis in these mice. This is manifested by increased periportal infiltrations, bile duct damage, granulomas and fibrosis. Interestingly, the BECs of Gal-3 knockout mice had a higher response to apoptotic stimuli and there were more pro-inflammatory lymphocytes and dendritic cells (DCs) in the livers of Gal-3 knockout mice. In conclusion, Gal-3 plays a protective role in the pathways that lead to the inflammatory destruction of biliary epithelial cells.
Acid-sensing ion channel 1a contributes to hippocampal LTP inducibility through multiple mechanisms
Authors: Liu Ming-Gang , Li Hu-Song , Li Wei-Guang , Wu Yan-Jiao , Deng Shi-Ning , Huang Chen , Maximyuk Oleksandr , Sukach Volodymyr , Krishtal Oleg , Zhu Michael X. , Xu Tian-Le
Published: March 2016

The exact roles of acid-sensing ion channels (ASICs) in synaptic plasticity remain elusive. Here, we address the contribution of ASIC1a to five forms of synaptic plasticity in the mouse hippocampus using an in vitro multi-electrode array recording system. We found that genetic deletion or pharmacological blockade of ASIC1a greatly reduced, but did not fully abolish, the probability of long-term potentiation (LTP) induction by either single or repeated high frequency stimulation or theta burst stimulation in the CA1 region. However, these treatments did not affect hippocampal long-term depression induced by low frequency electrical stimulation or (RS)-3,5-dihydroxyphenylglycine. We also show that ASIC1a exerts its action in hippocampal LTP through multiple mechanisms that include but are not limited to augmentation of NMDA receptor function. Taken together, these results reveal new insights into the role of ASIC1a in hippocampal synaptic plasticity and the underlying mechanisms. This unbiased study also demonstrates a novel and objective way to assay synaptic plasticity mechanisms in the brain.
Low-threshold optical bistability of graphene-wrapped dielectric composite
Authors: Huang Yang , Miroshnichenko Andrey E. , Gao Lei
Published: March 2016

We theoretically study the effective third-order nonlinear response and optical bistability of the 3D graphene based composite consisting of graphene wrapped dielectric nanoparticles embedded in dielectric host at terahertz frequencies. Taking into account the nonlinear conductivity of graphene, we derive the analytical expressions for the effective third-order nonlinear coefficient "Equation missing" in weakly nonlinear limit. Moreover, for strong applied fields, the criterion for achieving optical bistability in such a graphene coated sphere, as well as the switching thresholds of optical bistability are discussed. We find that both "Equation missing" and optical bistability are strongly dependent on the Fermi energy of graphene and it is possible to achieve very low switching thresholds under the normal graphene dissipation. We further propose a scheme to study the transmittance of this nonlinear composite slab. These results reveal novel regime of the optical bistability of the transmittance of light. We show that this kind of graphene-wrapped composite, which has tunable and low threshold optical bistability, can be the best candidate for unique nonlinear optical materials.
An unexpected advantage of insectivorism: insect moulting hormones ingested by song birds affect their ticks
Authors: Hornok Sándor , Kováts Dávid , Flaisz Barbara , Csörgő Tibor , Könczöl Árpád , Balogh György Tibor , Csorba Attila , Hunyadi Attila
Published: March 2016

Ecdysteroids are important hormones that regulate moulting in arthropods. Three-host ixodid ticks normally moult to the next stage after finishing their blood meal, in the off-host environment. Presumably, three-host ticks that feed on the blood of insectivorous vertebrate hosts can be exposed to high levels of exogenous ecdysteroids causing them to initiate apolysis (the first step of moulting) on the vertebrate host. The aim of the present study was to investigate whether ticks undergo apolysis on insectivorous song birds and if this phenomenon is associated with the seasonal variation in the availability of moths and with the presence of naturally acquired ecdysteroids in avian blood. During a triannual survey, 3330 hard tick larvae and nymphs were collected from 1164 insectivorous song birds of 46 species. A noteworthy proportion of ticks, 20.5%, showed apolysis. The occurrence of apolytic ticks on birds was correlated with the known seasonality of lepidopteran caterpillars. In addition, 18 blood samples of tick-infested birds were analysed with liquid chromatography – tandem mass spectrometry. Eight samples contained ecdysteroids or their derivatives, frequently in high concentrations and the presence of these was associated with tick apolysis. In conclusion, naturally acquired ecdysteroids may reach high levels in the blood of insectivorous passerine birds and will affect ticks (feeding on such blood) by shortening their parasitism.
23327Enhanced photoelectric conversion efficiency of dye-sensitized solar cells by the incorporation of flower-like Bi2S3:Eu3+ sub-microspheres
Authors: Xu Bingyu , Wang Guofeng , Fu Honggang
Published: March 2016

In this paper, TiO2-Bi2S3 and TiO2-Bi2S3:Eu3+ composite photoanodes were successfully designed, which can not only fully absorb visible light but also transfer the electron from Bi2S3 to TiO2 conduction band due to the narrow band gap and high conduction band of Bi2S3. Compared to pure TiO2 cell, the photoelectric conversion efficiencies of TiO2-Bi2S3 and TiO2-Bi2S3:Eu3+ composite cells were increased significantly. In addition, the efficiency of TiO2-Bi2S3:Eu3+ composite cells were higher than that of TiO2-Bi2S3 cell which could be attributed to the larger BET surface area of Bi2S3:Eu3+. The electron transport and interfacial recombination kinetics were investigated by the electrochemical impedance spectroscopy and intensity-modulated photocurrent/photovoltage spectroscopy. The results indicated that the interfacial resistance of the TiO2-dye|I3−/I− electrolyte interface of TiO2-Bi2S3:Eu3+ composite cell was much bigger than that of pure TiO2 cell. In addition, the TiO2-Bi2S3:Eu3+ cell has longer electron recombination time and longer electron transport time than pure TiO2 cell. The charge collection efficiency of TiO2-Bi2S3:Eu3+ composite cell was higher than that of pure TiO2 cell.
Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation
Authors: Chang Tien-Jyun , Tseng Hsing-Chi , Liu Meng-Wei , Chang Yi-Cheng , Hsieh Meng-Lun , Chuang Lee-Ming
Published: March 2016

Accumulation of methylglyoxal (MG) contributes to glucotoxicity and mediates beta cell apoptosis. The molecular mechanism by which GLP-1 protects MG-induced beta cell apoptosis remains unclear. Metformin is a first-line drug for treating type 2 diabetes associated with AMPK activation. However, whether metformin prevents MG-induced beta cell apoptosis is controversial. Here, we explored the signaling pathway involved in the anti-apoptotic effect of GLP-1, and investigated whether metformin had an anti-apoptotic effect on beta cells. MG treatment induced apoptosis of beta cells, impaired mitochondrial function, and prolonged activation of AMP-dependent protein kinase (AMPK). The MG-induced pro-apoptotic effects were abolished by an AMPK inhibitor. Pretreatment of GLP-1 reversed MG-induced apoptosis, and mitochondrial dysfunction, and suppressed prolonged AMPK activation. Pretreatment of GLP-1 reversed AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR)-induced apoptosis, and suppressed prolonged AMPK activation. However, metformin neither leads to beta cell apoptosis nor ameliorates MG-induced beta cell apoptosis. In parallel, GLP-1 also prevents MG-induced beta cell apoptosis through PKA and PI3K-dependent pathway. In conclusion, these data indicates GLP-1 but not metformin protects MG-induced beta cell apoptosis through improving mitochondrial function, and alleviating the prolonged AMPK activation. Whether adding GLP-1 to metformin provides better beta cell survival and delays disease progression remains to be validated.
Associations between nitric oxide synthase 3 gene polymorphisms and preeclampsia risk: a meta-analysis
Authors: Zeng Fangfang , Zhu Sui , Wong Martin Chi-Sang , Yang Zuyao , Tang Jinling , Li Keshen , Su Xuefen
Published: March 2016

Previous studies have examined the role of three NOS3 gene polymorphisms [G894T, T-786C and the variable number of tandem repeats 4b/a (VNTR 4b/a)] in the susceptibility to preeclampsia with inconclusive findings. We therefore conducted an updated meta-analysis by including more studies. The most appropriate genetic model was chosen for each polymorphism by using a well-established method. Pooled results indicated that, compared with the GT + GG genotype, the TT genotype of G894T was associated with an increased risk of preeclampsia (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.21–1.77, P < 0.001; I2 = 40.2%). The CC genotype of T-786C was also associated with a higher risk of preeclampsia (OR = 1.30; 95% CI = 1.07–1.58, P = 0.034; I2 = 46.9%) than the CT + TT genotype. No association was found for VNTR 4b/a. Stratified analysis indicated that the increased risk was evident for high-quality studies both for G894T and T-786C and for studies conducted among Caucasians and Africans for T-786C. However, the increased risk for T-786C among Africans needs further confirmation due to the high probability of false-positive reports. Our results suggested that G894T and T-786C polymorphisms, but not VNTR 4b/a, were associated with an increased risk of preeclampsia.
Impact of the representation of stomatal conductance on model projections of heatwave intensity
Authors: Kala Jatin , De Kauwe Martin G. , Pitman Andy J. , Medlyn Belinda E. , Wang Ying-Ping , Lorenz Ruth , Perkins-Kirkpatrick Sarah E.
Published: March 2016

Stomatal conductance links plant water use and carbon uptake and is a critical process for the land surface component of climate models. However, stomatal conductance schemes commonly assume that all vegetation with the same photosynthetic pathway use identical plant water use strategies whereas observations indicate otherwise. Here, we implement a new stomatal scheme derived from optimal stomatal theory and constrained by a recent global synthesis of stomatal conductance measurements from 314 species, across 56 field sites. Using this new stomatal scheme, within a global climate model, subtantially increases the intensity of future heatwaves across Northern Eurasia. This indicates that our climate model has previously been under-predicting heatwave intensity. Our results have widespread implications for other climate models, many of which do not account for differences in stomatal water-use across different plant functional types and hence, are also likely under projecting heatwave intensity in the future.
Combination of simvastatin, calcium silicate/gypsum, and gelatin and bone regeneration in rabbit calvarial defects
Authors: Zhang Jing , Wang Huiming , Shi Jue , Wang Ying , Lai Kaichen , Yang Xianyan , Chen Xiaoyi , Yang Guoli
Published: March 2016

The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm-diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin-loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration.
Fabrication, characterization, and biological assessment of multilayer laminin γ2 DNA coatings on titanium surfaces
Authors: Yang Guoli , Zhang Jing , Dong Wenjing , Liu Li , Shi Jue , Wang Huiming
Published: March 2016

The purpose of this work was to fabricate a multilayer laminin γ2 DNA coating on a titanium surface and evaluate its biological properties. A multilayer laminin γ2 DNA coating was fabricated on titanium using a layer-by-layer assembly technique. The rate of coating degradation was evaluated by detecting the amount of cDNA remaining. Surface analysis using X-ray photoelectron spectroscopy, atomic force microscopy, and surface contact angle measurements revealed the multilayer structure to consist of cationic lipid and confirmed that a laminin γ2 DNA layer could be fabricated on titanium via the layer-by-layer assembly process. The transfection efficiency was highest for five layers in the multilayer structure. HEK293 cells cultured on the multilayer films displayed significantly higher adhesion activity than the control group. The expression of laminin γ2 and the co-localization of integrin β4 and plectin were more obvious in HN4 cells cultured on the multilayer laminin γ2 DNA coating, while weak immunoreactivities were observed in the control group. We concluded that the DNA-loaded multilayer provided a surface with good biocompatibility and that the multilayer laminin γ2 DNA coating might be effective in improving cell adhesion and the formation of hemidesmosomes on titanium surfaces.
Characterization of the Plasmodium Interspersed Repeats (PIR) proteins of Plasmodium chabaudi indicates functional diversity
Authors: Yam Xue Yan , Brugat Thibaut , Siau Anthony , Lawton Jennifer , Wong Daniel S. , Farah Abdirahman , Twang Jing Shun , Gao Xiaohong , Langhorne Jean , Preiser Peter R.
Published: March 2016

Plasmodium multigene families play a central role in the pathogenesis of malaria. The Plasmodium interspersed repeat (pir) genes comprise the largest multigene family in many Plasmodium spp. However their function(s) remains unknown. Using the rodent model of malaria, Plasmodium chabaudi, we show that individual CIR proteins have differential localizations within infected red cell (iRBC), suggesting different functional roles in a blood-stage infection. Some CIRs appear to be located on the surface of iRBC and merozoites and are therefore well placed to interact with host molecules. In line with this hypothesis, we show for the first time that a subset of recombinant CIRs bind mouse RBCs suggesting a role for CIR in rosette formation and/or invasion. Together, our results unravel differences in subcellular localization and ability to bind mouse erythrocytes between the members of the cir family, which strongly suggest different functional roles in a blood-stage infection.
Gradient Permittivity Meta-Structure model for Wide-field Super-resolution imaging with a sub-45 nm resolution
Authors: Cao Shun , Wang Taisheng , Xu Wenbin , Liu Hua , Zhang Hongxin , Hu Bingliang , Yu Weixing
Published: March 2016

A gradient permittivity meta-structure (GPMS) model and its application in super-resolution imaging were proposed and discussed in this work. The proposed GPMS consists of alternate metallic and dielectric films with a gradient permittivity which can support surface plasmons (SPs) standing wave interference patterns with a super resolution. By employing the rigorous numerical FDTD simulation method, the GPMS was carefully simulated to find that the period of the SPs interference pattern is only 84 nm for a 532 nm incident light. Furthermore, the potential application of the GPMS for wide-field super-resolution imaging was also discussed and the simulation results show that an imaging resolution of sub−45 nm can be achieved based on the plasmonic structure illumination microscopic method, which means a 5.3-fold improvement on resolution has been achieved in comparison with conventional epifluorescence microscopy. Moreover, besides the super-resolution imaging application, the proposed GPMS model can also be applied for nanolithography and other areas where super resolution patterns are needed.
Lighting Up Clostridium Difficile: Reporting Gene Expression Using Fluorescent Lov Domains
Authors: Buckley Anthony M. , Jukes Caitlin , Candlish Denise , Irvine June J. , Spencer Janice , Fagan Robert P. , Roe Andrew J. , Christie John M. , Fairweather Neil F. , Douce Gillian R.
Published: March 2016

The uses of fluorescent reporters derived from green fluorescent protein have proved invaluable for the visualisation of biological processes in bacteria grown under aerobic conditions. However, their requirement for oxygen has limited their application in obligate anaerobes such as Clostridium difficile. Fluorescent proteins derived from Light, Oxygen or Voltage sensing (LOV) domains have been shown to bridge this limitation, but their utility as translational fusions to monitor protein expression and localisation in a strict anaerobic bacterium has not been reported. Here we demonstrate the utility of phiLOV in three species of Clostridium and its application as a marker of real-time protein translation and dynamics through genetic fusion with the cell division protein, FtsZ. Time lapse microscopy of dividing cells suggests that Z ring assembly arises through the extension of the FtsZ arc starting from one point on the circumference. Furthermore, through incorporation of phiLOV into the flagella subunit, FliC, we show the potential of bacterial LOV-based fusion proteins to be successfully exported to the extracellular environment.
Ancient DNA reveals selection acting on genes associated with hypoxia response in pre-Columbian Peruvian Highlanders in the last 8500 years
Authors: Fehren-Schmitz Lars , Georges Lea
Published: March 2016

Archaeological evidence shows that humans began living in the high altitude Andes approximately 12,000 years ago. Andean highlanders are known to have developed the most complex societies of pre-Columbian South America despite challenges to their health and reproductive success resulting from chronic exposure to hypoxia. While the physiological adaptations to this environmental stressor are well studied in contemporary Andean highlanders, the molecular evolutionary processes associated with such adaptations remain unclear. We aim to better understand how humans managed to demographically establish in this harsh environment by addressing a central question: did exposure to hypoxia drive adaptation via natural selection within Andean populations or did an existing phenotype –characterized by reduced susceptibility to hypoxic stress–enable human settlement of the Andes? We genotyped three variable loci within theNOS3andEGLN1genes previously associated with adaptation to high altitude in 150 ancient human DNA samples from Peruvian high altitude and coastal low altitude sites in a time frame between ~8500–560 BP. We compare the data of 109 successful samples to forward simulations of genetic drift with natural selection and find that selection, rather than drift, explains the gradual frequency changes observed in the highland populations for two of the three SNPs.
Hxt13, Hxt15, Hxt16 and Hxt17 from Saccharomyces cerevisiae represent a novel type of polyol transporters
Authors: Jordan Paulina , Choe Jun-Yong , Boles Eckhard , Oreb Mislav
Published: March 2016

The genome of S. cerevisae encodes at least twenty hexose transporter-like proteins. Despite extensive research, the functions of Hxt8-Hxt17 have remained poorly defined. Here, we show that Hxt13, Hxt15, Hxt16 and Hxt17 transport two major hexitols in nature, mannitol and sorbitol, with moderate affinities, by a facilitative mechanism. Moreover, Hxt11 and Hxt15 are capable of transporting xylitol, a five-carbon polyol derived from xylose, the most abundant pentose in lignocellulosic biomass. Hxt11, Hxt13, Hxt15, Hxt16 and Hxt17 are phylogenetically and functionally distinct from known polyol transporters. Based on docking of polyols to homology models of transporters, we propose the architecture of their active site. In addition, we determined the kinetic parameters of mannitol and sorbitol dehydrogenases encoded in the yeast genome, showing that they discriminate between mannitol and sorbitol to a much higher degree than the transporters.
HIV-1 cellular and tissue replication patterns in infected humanized mice
Authors: Araínga Mariluz , Su Hang , Poluektova Larisa Y. , Gorantla Santhi , Gendelman Howard E.
Published: March 2016

Humanized mice have emerged as a testing platform for HIV-1 pathobiology by reflecting natural human disease processes. Their use to study HIV-1 biology, virology, immunology, pathogenesis and therapeutic development has served as a robust alternative to more-well developed animal models for HIV/AIDS. A critical component in reflecting such human pathobiology rests in defining the tissue and cellular sites for HIV-1 infection. To this end, we examined the tissue sites for viral infection in bone marrow, blood, spleens, liver, gut, brain, kidney and lungs of human CD34+ hematopoietic stem cell engrafted virus-infected NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice. Cells were analyzed by flow cytometry and sorted from species mixtures defined as CD34+ lineage negative progenitor cells, CD14+CD16+ monocyte-macrophages and central, stem cell and effector memory T cells. The cell distribution and viral life cycle were found dependent on the tissue compartment and time of infection. Cell subsets contained HIV-1 total and integrated DNA as well as multi-spliced and unspliced RNA in divergent proportions. The data support the idea that humanized mice can provide a means to examine the multifaceted sites of HIV-1 replication including, but not limited to progenitor cells and monocyte-macrophages previously possible only in macaques and human.
Probiotic supplementation does not improve eradication rate of Helicobacter pylori infection compared to placebo based on standard therapy: a meta-analysis
Authors: Lu Chao , Sang Jianzhong , He Haijian , Wan Xingyong , Lin Yiming , Li Lan , Li Youming , Yu Chaohui
Published: March 2016

This meta-analysis included eligible randomized controlled trials (RCTs) with the aim of determining whether probiotic supplementation can improve H. pylori eradication rates. PUBMED, EBSCO, Web of Science and Ovid databases were searched. We included RCTs that investigated the effect of combining probiotics, with or without a placebo, with standard therapy. A total of 21 RCTs that reported standard therapy plus probiotics were included. Compared to the placebo group, the probiotics group was 1.21(OR 1.21, 95% CI: 0.86, 1.69) and 1.28 (OR 1.28, 95% CI: 0.88, 1.86) times more likely to achieve eradication of H. pylori infection in intent-to-treat (ITT) analysis and per protocol (PP) analysis, respectively. Probiotics with triple therapy plus a 14-day course of treatment did not improve the eradication of H. pylori infection (OR 1.44, 95% CI: 0.87, 2.39) compared to the placebo. Moreover, the placebo plus standard therapy did not improve eradication rates compared to standard therapy alone (P = 0.816). However, probiotics did improve the adverse effects of diarrhea and nausea. These pooled data suggest that the use of probiotics plus standard therapy does not improve the eradication rate of H. pylori infection compared to the placebo.