bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomimetic temporal self-assembly via fuel-driven controlled supramolecular polymerization
Authors: Mishra Ananya , Korlepara Divya B. , Kumar Mohit , Jain Ankit , Jonnalagadda Narendra , Bejagam Karteek K. , Balasubramanian Sundaram , George Subi J. 
Published: April 2018

AbstractTemporal control of supramolecular assemblies to modulate the structural and transient characteristics of synthetic nanostructures is an active field of research within supramolecular chemistry. Molecular designs to attain temporal control have often taken inspiration from biological assemblies. One such assembly in Nature which has been studied extensively, for its well-defined structure and programmable self-assembly, is the ATP-driven seeded self-assembly of actin. Here we show, in a synthetic manifestation of actin self-assembly, an ATP-selective and ATP-fuelled, controlled supramolecular polymerization of a phosphate receptor functionalised monomer. It undergoes fuel-driven nucleation and seeded growth that provide length control and narrow dispersity of the resultant assemblies. Furthermore, coupling via ATP-hydrolysing enzymes yielded its transient characteristics. These results will usher investigations into synthetic analogues of important biological self-assembly motifs and will prove to be a significant advancement toward biomimetic temporally programmed materials.
Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds
Authors: Zhu Lizhi , Ma Wenjing , Zhang Mengxun , Lee Magnolia Muk-Lan , Wong Wing-Yan , Chan Brandon Dow , Yang Qianqian , Wong Wing-Tak , Tai William Chi-Shing , Lee Chi-Sing 
Published: April 2018

AbstractChallenges in the development of anti-cancer chemotherapeutics continue to exist, particularly with respect to adverse effects and development of resistance, underlining the need for novel drugs with good safety profiles. Natural products have proven to be a fertile ground for exploitation, and development of anti-cancer drugs from structurally complex natural products holds promise. Unfortunately, this approach is often hindered by low isolation yields and limited information from preliminary cell-based assays. Here we report a concise and scalable synthesis of a series of low-abundance Isodon diterpenoids (a large class of natural products with over 1000 members isolated from the herbs of genus Isodon, which are well-known folk medicines for the treatment of inflammation and cancer), including eriocalyxin B, neolaxiflorin L and xerophilusin I. These scalable syntheses enable multilevel bio-evaluation of the natural products, in which we identify neolaxiflorin L as a promising anti-cancer drug candidate.
Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria
Authors: Matic Stanka , Jiang Min , Nicholls Thomas J. , Uhler Jay P. , Dirksen-Schwanenland Caren , Polosa Paola Loguercio , Simard Marie-Lune , Li Xinping , Atanassov Ilian , Rackham Oliver , Filipovska Aleksandra , Stewart James B. , Falkenberg Maria , Larsson Nils-Göran , Milenkovic Dusanka 
Published: April 2018

AbstractReplication of mammalian mitochondrial DNA (mtDNA) is an essential process that requires high fidelity and control at multiple levels to ensure proper mitochondrial function. Mutations in the mitochondrial genome maintenance exonuclease 1 (MGME1) gene were recently reported in mitochondrial disease patients. Here, to study disease pathophysiology, we generated Mgme1 knockout mice and report that homozygous knockouts develop depletion and multiple deletions of mtDNA. The mtDNA replication stalling phenotypes vary dramatically in different tissues of Mgme1 knockout mice. Mice with MGME1 deficiency accumulate a long linear subgenomic mtDNA species, similar to the one found in mtDNA mutator mice, but do not develop progeria. This finding resolves a long-standing debate by showing that point mutations of mtDNA are the main cause of progeria in mtDNA mutator mice. We also propose a role for MGME1 in the regulation of replication and transcription termination at the end of the control region of mtDNA.
Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells
Authors: Takahashi Akiko , Loo Tze Mun , Okada Ryo , Kamachi Fumitaka , Watanabe Yoshihiro , Wakita Masahiro , Watanabe Sugiko , Kawamoto Shimpei , Miyata Kenichi , Barber Glen N. , Ohtani Naoko , Hara Eiji 
Published: April 2018

AbstractAccumulating evidence indicates that the senescence-associated secretory phenotype (SASP) contributes to many aspects of physiology and disease. Thus, controlling the SASP will have tremendous impacts on our health. However, our understanding of SASP regulation is far from complete. Here, we show that cytoplasmic accumulation of nuclear DNA plays key roles in the onset of SASP. Although both DNase2 and TREX1 rapidly remove the cytoplasmic DNA fragments emanating from the nucleus in pre-senescent cells, the expression of these DNases is downregulated in senescent cells, resulting in the cytoplasmic accumulation of nuclear DNA. This causes the aberrant activation of cGAS-STING cytoplasmic DNA sensors, provoking SASP through induction of interferon-β. Notably, the blockage of this pathway prevents SASP in senescent hepatic stellate cells, accompanied by a decline of obesity-associated hepatocellular carcinoma development in mice. These findings provide valuable new insights into the roles and mechanisms of SASP and possibilities for their control.
Spatial fidelity of workers predicts collective response to disturbance in a social insect
Authors: Crall James D. , Gravish Nick , Mountcastle Andrew M. , Kocher Sarah D. , Oppenheimer Robert L. , Pierce Naomi E. , Combes Stacey A. 
Published: April 2018

AbstractIndividuals in social insect colonies cooperate to perform collective work. While colonies often respond to changing environmental conditions by flexibly reallocating workers to different tasks, the factors determining which workers switch and why are not well understood. Here, we use an automated tracking system to continuously monitor nest behavior and foraging activity of uniquely identified workers from entire bumble bee (Bombus impatiens) colonies foraging in a natural outdoor environment. We show that most foraging is performed by a small number of workers and that the intensity and distribution of foraging is actively regulated at the colony level in response to forager removal. By analyzing worker nest behavior before and after forager removal, we show that spatial fidelity of workers within the nest generates uneven interaction with relevant localized information sources, and predicts which workers initiate foraging after disturbance. Our results highlight the importance of spatial fidelity for structuring information flow and regulating collective behavior in social insect colonies.
Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction
Authors: Weinhard Laetitia , di Bartolomei Giulia , Bolasco Giulia , Machado Pedro , Schieber Nicole L. , Neniskyte Urte , Exiga Melanie , Vadisiute Auguste , Raggioli Angelo , Schertel Andreas , Schwab Yannick , Gross Cornelius T. 
Published: April 2018

AbstractMicroglia are highly motile glial cells that are proposed to mediate synaptic pruning during neuronal circuit formation. Disruption of signaling between microglia and neurons leads to an excess of immature synaptic connections, thought to be the result of impaired phagocytosis of synapses by microglia. However, until now the direct phagocytosis of synapses by microglia has not been reported and fundamental questions remain about the precise synaptic structures and phagocytic mechanisms involved. Here we used light sheet fluorescence microscopy to follow microglia–synapse interactions in developing organotypic hippocampal cultures, complemented by a 3D ultrastructural characterization using correlative light and electron microscopy (CLEM). Our findings define a set of dynamic microglia–synapse interactions, including the selective partial phagocytosis, or trogocytosis (trogo-: nibble), of presynaptic structures and the induction of postsynaptic spine head filopodia by microglia. These findings allow us to propose a mechanism for the facilitatory role of microglia in synaptic circuit remodeling and maturation.
Integrative proteomics in prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression
Authors: Latonen Leena , Afyounian Ebrahim , Jylhä Antti , Nättinen Janika , Aapola Ulla , Annala Matti , Kivinummi Kati K. , Tammela Teuvo T. L. , Beuerman Roger W. , Uusitalo Hannu , Nykter Matti , Visakorpi Tapio 
Published: April 2018

AbstractTo understand functional consequences of genetic and transcriptional aberrations in prostate cancer, the proteomic changes during disease formation and progression need to be revealed. Here we report high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. By integrative analysis we show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes. Instead, we uncover previously unrecognized molecular and pathway events, for example, several miRNA target correlations present at protein but not at mRNA level. Notably, we identify two metabolic shifts in the citric acid cycle (TCA cycle) during prostate cancer development and progression. Our proteogenomic analysis uncovers robustness against genomic and transcriptomic aberrations during prostate cancer progression, and significantly extends understanding of prostate cancer disease mechanisms.
Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice
Authors: Shang Congping , Chen Zijun , Liu Aixue , Li Yang , Zhang Jiajing , Qu Baole , Yan Fei , Zhang Yaning , Liu Weixiu , Liu Zhihui , Guo Xiaofei , Li Dapeng , Wang Yi , Cao Peng 
Published: April 2018

AbstractAnimals respond to environmental threats, e.g. looming visual stimuli, with innate defensive behaviors such as escape and freezing. The key neural circuits that participate in the generation of such dimorphic defensive behaviors remain unclear. Here we show that the dimorphic behavioral patterns triggered by looming visual stimuli are mediated by parvalbumin-positive (PV+) projection neurons in mouse superior colliculus (SC). Two distinct groups of SC PV+ neurons form divergent pathways to transmit threat-relevant visual signals to neurons in the parabigeminal nucleus (PBGN) and lateral posterior thalamic nucleus (LPTN). Activations of PV+ SC-PBGN and SC-LPTN pathways mimic the dimorphic defensive behaviors. The PBGN and LPTN neurons are co-activated by looming visual stimuli. Bilateral inactivation of either nucleus results in the defensive behavior dominated by the other nucleus. Together, these data suggest that the SC orchestrates dimorphic defensive behaviors through two separate tectofugal pathways that may have interactions.
AUX1-mediated root hair auxin influx governs SCFTIR1/AFB-type Ca2+ signaling
Authors: Dindas Julian , Scherzer Sönke , Roelfsema M. Rob G. , von Meyer Katharina , Müller Heike M. , Al-Rasheid K. A. S. , Palme Klaus , Dietrich Petra , Becker Dirk , Bennett Malcolm J. , Hedrich Rainer 
Published: April 2018

AbstractAuxin is a key regulator of plant growth and development, but the causal relationship between hormone transport and root responses remains unresolved. Here we describe auxin uptake, together with early steps in signaling, inArabidopsisroot hairs. Using intracellular microelectrodes we show membrane depolarization, in response to IAA in a concentration- and pH-dependent manner. This depolarization is strongly impaired inaux1mutants, indicating that AUX1 is the major transporter for auxin uptake in root hairs. Local intracellular auxin application triggers Ca2+signals that propagate as long-distance waves between root cells and modulate their auxin responses. AUX1-mediated IAA transport, as well as IAA-triggered calcium signals, are blocked by treatment with the SCFTIR1/AFB- inhibitor auxinole. Further, they are strongly reduced in thetir1afb2afb3and thecngc14mutant. Our study reveals that the AUX1 transporter, the SCFTIR1/AFBreceptor and the CNGC14 Ca2+channel, mediate fast auxin signaling in roots.
Fluorescent label-free quantitative detection of nano-sized bioparticles using a pillar array
Authors: Zeming Kerwin Kwek , Salafi Thoriq , Shikha Swati , Zhang Yong 
Published: April 2018

AbstractDisease diagnostics requires detection and quantification of nano-sized bioparticles including DNA, proteins, viruses, and exosomes. Here, a fluorescent label-free method for sensitive detection of bioparticles is explored using a pillar array with micrometer-sized features in a deterministic lateral displacement (DLD) device. The method relies on measuring changes in size and/or electrostatic charges of 1 µm polymer beads due to the capture of target bioparticles on the surface. These changes can be sensitively detected through the lateral displacement of the beads in the DLD array, wherein the lateral shifts in the output translates to a quantitative measurement of bioparticles bound to the bead. The detection of albumin protein and nano-sized polymer vesicles with a concentration as low as 10 ng mL−1 (150 pM) and 3.75 μg mL−1, respectively, is demonstrated. This label-free method holds potential for point-of-care diagnostics, as it is low-cost, fast, sensitive, and only requires a standard laboratory microscope for detection.
Experimentally quantifying anion polarizability at the air/water interface
Authors: Tong Yujin , Zhang Igor Ying , Campen R. Kramer 
Published: April 2018

AbstractThe adsorption of large, polarizable anions from aqueous solution on the air/water interface controls important atmospheric chemistry and is thought to resemble anion adsorption at hydrophobic interfaces generally. While the favourability of adsorption of such ions is clear, quantifying adsorption thermodynamics has proven challenging because it requires accurate description of the structure of the anion and its solvation shell at the interface. In principle anion polarizability offers a structural window, but to the best of our knowledge there has so far been no experimental technique that allowed its characterization with interfacial specificity. Here, we meet this challenge using interface-specific vibrational spectroscopy of Cl–O vibrations of the $${\mathrm{ClO}}_4^ -$$

ClO

4

-

anion at the air/water interface and report that the interface breaks the symmetry of the anion, the anisotropy of $${\mathrm{ClO}}_4^ -$$

ClO

4

-

’s polarizability tensor is more than two times larger than in bulk water and concentration dependent, and concentration-dependent polarizability changes are consistent with correlated changes in surface tension.
Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1
Authors: Su Qiang , Hu Feizhuo , Liu Yuxia , Ge Xiaofei , Mei Changlin , Yu Shengqiang , Shen Aiwen , Zhou Qiang , Yan Chuangye , Lei Jianlin , Zhang Yanqing , Liu Xiaodong , Wang Tingliang 
Published: April 2018

AbstractPKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 Å resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned. Unlike its ortholog PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are involved in upper and lower-gate opening, adopt an open conformation. Structural comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore domain dilation is coupled to conformational changes of voltage-sensing domains (VSDs) via a series of π–π interactions, suggesting a potential PKD2L1 gating mechanism.
The oldest magnetic record in our solar system identified using nanometric imaging and numerical modeling
Authors: Shah Jay , Williams Wyn , Almeida Trevor P. , Nagy Lesleis , Muxworthy Adrian R. , Kovács András , Valdez-Grijalva Miguel A. , Fabian Karl , Russell Sara S. , Genge Matthew J. , Dunin-Borkowski Rafal E. 
Published: April 2018

AbstractRecordings of magnetic fields, thought to be crucial to our solar system’s rapid accretion, are potentially retained in unaltered nanometric low-Ni kamacite (~ metallic Fe) grains encased within dusty olivine crystals, found in the chondrules of unequilibrated chondrites. However, most of these kamacite grains are magnetically non-uniform, so their ability to retain four-billion-year-old magnetic recordings cannot be estimated by previous theories, which assume only uniform magnetization. Here, we demonstrate that non-uniformly magnetized nanometric kamacite grains are stable over solar system timescales and likely the primary carrier of remanence in dusty olivine. By performing in-situ temperature-dependent nanometric magnetic measurements using off-axis electron holography, we demonstrate the thermal stability of multi-vortex kamacite grains from the chondritic Bishunpur meteorite. Combined with numerical micromagnetic modeling, we determine the stability of the magnetization of these grains. Our study shows that dusty olivine kamacite grains are capable of retaining magnetic recordings from the accreting solar system.
Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination
Authors: Costanzo Margaret C. , Kim Dohoon , Creegan Matthew , Lal Kerri G. , Ake Julie A. , Currier Jeffrey R. , Streeck Hendrik , Robb Merlin L. , Michael Nelson L. , Bolton Diane L. , Steers Nicholas J. , Eller Michael A. 
Published: April 2018

AbstractNatural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK cells responding to models of direct cell recognition, ADCC, and cytokine activation have unique transcriptional fingerprints. Compared with healthy volunteers, individuals with chronic HIV-1 infection have higher expression of genes commonly associated with activation, and lower expression of genes associated with direct cell recognition and cytokine stimulation in their NK cells. By contrast, NK cell transcriptional profiles of individuals receiving a modified vaccinia Ankara (MVA) vectored HIV-1 vaccine show upregulation of genes associated with direct cell recognition. These findings demonstrate that targeted transcriptional profiling provides a sensitive assessment of NK cell activity, which helps understand how NK cells respond to viral infections and vaccination.
Conformational switching within dynamic oligomers underpins toxic gain-of-function by diabetes-associated amyloid
Authors: Birol Melissa , Kumar Sunil , Rhoades Elizabeth , Miranker Andrew D. 
Published: April 2018

AbstractPeptide mediated gain-of-toxic function is central to pathology in Alzheimer’s, Parkinson’s and diabetes. In each system, self-assembly into oligomers is observed and can also result in poration of artificial membranes. Structural requirements for poration and the relationship of structure to cytotoxicity is unaddressed. Here we focus on islet amyloid polypeptide (IAPP) mediated loss-of-insulin secreting cells in patients with diabetes. Newly developed methods enable structure-function enquiry to focus on intracellular oligomers composed of hundreds of IAPP. The key insights are that porating oligomers are internally dynamic, grow in discrete steps and are not canonical amyloid. Moreover, two classes of poration occur; an IAPP-specific ligand establishes that only one is cytotoxic. Toxic rescue occurs by stabilising non-toxic poration without displacing IAPP from mitochondria. These insights illuminate cytotoxic mechanism in diabetes and also provide a generalisable approach for enquiry applicable to other partially ordered protein assemblies.
Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells
Authors: Cencioni Chiara , Spallotta Francesco , Savoia Matteo , Kuenne Carsten , Guenther Stefan , Re Agnese , Wingert Susanne , Rehage Maike , Sürün Duran , Siragusa Mauro , Smith Jacob G. , Schnütgen Frank , von Melchner Harald , Rieger Michael A. , Martelli Fabio , Riccio Antonella , Fleming Ingrid , Braun Thomas , Zeiher Andreas M. , Farsetti Antonella , Gaetano Carlo 
Published: April 2018

AbstractNitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.
Synthesis of AgN5 and its extended 3D energetic framework
Authors: Sun Chengguo , Zhang Chong , Jiang Chao , Yang Chen , Du Yang , Zhao Yue , Hu Bingcheng , Zheng Zhansheng , Christe Karl O. 
Published: April 2018

AbstractThe pentazolate anion, as a polynitrogen species, holds great promise as a high-energy density material for explosive or propulsion applications. Designing pentazole complexes that contain minimal non-energetic components is desirable in order to increase the material’s energy density. Here, we report a solvent-free pentazolate complex, AgN5, and a 3D energetic-framework, [Ag(NH3)2]+[Ag3(N5)4]ˉ, constructed from silver and cyclo-N5ˉ. The complexes are stable up to 90 °C and only Ag and N2 are observed as the final decomposition products. Efforts to isolate pure AgN5 were unsuccessful due to partial photolytical and/or thermal-decomposition to AgN3. Convincing evidence for the formation of AgN5 as the original reaction product is presented. The isolation of a cyclo-N5ˉ complex, devoid of stabilizing molecules and ions, such as H2O, H3O+, and NH4+, constitutes a major advance in pentazole chemistry.
Two-component anomalous Hall effect in a magnetically doped topological insulator
Authors: Liu Nan , Teng Jing , Li Yongqing 
Published: April 2018

AbstractThe anomalous Hall (AH) effect measurement has emerged as a powerful tool to gain deep insights into magnetic materials, such as ferromagnetic metals, magnetic semiconductors, and magnetic topological insulators (TIs). In Mn-doped Bi2Se3, however, the AH effect has never been reported despite a lot of previous studies. Here we report the observation of AH effect in (Bi,Mn)2Se3 thin films and show that the sign of AH resistances changes from positive to negative as the Mn concentration is increased. The positive and negative AH resistances are found to coexist in a crossover regime. Such a two-component AH effect and the sign reversal can also be obtained by electrical gating of lightly doped samples. Our results provide an important basis for understanding the puzzling interplay between the surface states, the bulk states, and various magnetic doping effects, as well as competing magnetic orders in magnetically doped TIs.