bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractMicroRNA (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

AbstractDNA 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

AbstractIntraflagellar 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

AbstractOne 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.
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

AbstractThe 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

AbstractProteins 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

AbstractHaemosporida 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

AbstractTwo-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

AbstractThe 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

AbstractWe 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

AbstractWe 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

AbstractWe 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

AbstractThe 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

AbstractGalectin-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

AbstractThe 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

AbstractWe 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.