bluuebunny/crossref_metadata_2025 huggingface dataset:
An observationally based method for stratifying a priori passive microwave observations in a Bayesian‐based precipitation retrieval framework
Authors: Turk F. Joseph , Haddad Ziad S. , Kirstetter Pierre‐Emmanuel , You Yalei , Ringerud Sarah
Published: November 2017

Estimation of precipitation from space‐based passive microwave (PMW) radiometric brightness temperature (TB) observations that adapts to the wide variety of Earth surface background and environmental conditions is a long‐standing issue. Since these conditions are generally unknown from the TB observations, PMW‐based precipitation estimation techniques commonly utilize independent ancillary data sources, such as interpolated prognostic variables from numerical weather prediction forecast models, and discrete surface emissivity classifications. In some situations, the selection of these variables may restrain the algorithm performance under particular surface and atmospheric conditions. The objective of this article is to examine the emissivity principal component (EPC) analysis as a common stratification method for indexing, searching and weighting candidate precipitation profiles from a priori databases, adaptable for Bayesian‐based precipitation estimation algorithms applied to the Global Precipitation Measurement (GPM) Microwave Imager (GMI) or other PMW sensors, to minimize dependence upon ancillary data sources. The EPC has been previously shown to track the joint variability between the 10–89 GHz surface emissivity, total column precipitable water vapour (TPW) and surface temperature (Ts) conditions directly from the TB observations, and identify global locations of similar conditions. A parallel GMI precipitation retrieval was carried out where the identical a priori database was indexed by TPW, Ts and a surface emissivity class index. An independent validation of each precipitation retrieval scheme was carried out using GMI pixel‐matched Multi‐Radar Multi‐Source (MRMS) ground radar data over the continental USA and surrounding ocean waters. While the EPC‐based estimates demonstrated similar performance to the TPW‐based estimates over ocean backgrounds, a markedly improved detection, and reduction in bias, was found for moderate and higher (>5 mm/hr) rainfall rates over other backgrounds, especially vegetated surfaces and coastlines.
“Synthesis, Spectral Characterisation, Theoretical Investigations and Nonlinear Optical Properties of Ethyl 4‐(3‐(1, 3‐dimethyl‐1H‐pyrazole‐5‐carboxamido)phenyl)‐1,2,3,4‐tetrahydro‐6‐methyl‐2‐oxopyrimidine‐5‐carboxylate”
Authors: Adaikalaraj Chinnapan , Manivarman Subramanian
Published: November 2017

Newly synthesized nonlinear optical material is ethyl4‐(3‐(1,3‐dimethyl‐1H‐pyrazole‐5‐carboxamido)phenyl)‐1,2,3,4‐tetrahydro‐6‐methyl‐2‐oxopyrimidine‐5‐carboxylate (DMPC). It has been characterized experimentally by FT‐IR, FT‐Raman, 1H and 13C‐NMR spectrum and theoretically by DFT method using B3LYP/6‐31G(d,p) level of theory. A detailed interpretation of the vibrational spectrum was comparable with theoretical wavenumber using single scaling factor. The intra‐molecular charge transfers occurring in the molecule have been analyzed by donor‐acceptor interaction from natural bonding orbital analysis. The nonlinear optical activity of the compounds has been calculated, and found that the molecule is a good candidate of nonlinear material. The optical response and conduction nature of the title molecule have band gap of frontier edges were calculated by TD‐DFT calculation and these results studied with UV‐Visible spectrum. Especially the π‐π* bonding interactions were interested to study conjugative property of the molecule. Moreover, molecular electrostatic potential surface of DMPC are useful in investigating the stability and reactivity of the molecule
Nondestructive Method for the Determination of the Electric Polarization Orientation in Thin Films: Illustration on Gallium Ferrite Thin Films
Authors: Lefevre Chistophe , Demchenko Anna , Bouillet Corinne , Luysberg Martina , Devaux Xavier , Roulland François , Versini Gilles , Barre Sophie , Wakabayashi Yusuke , Boudet Nathalie , Leuvrey Cédric , Acosta Manuel , Meny Christian , Martin Elodie , Grenier Stéphane , Favre‐Nicolin Vincent , Viart Nathalie
Published: November 2017

The knowledge and control of the electric polarization in multiferroic thin films is currently the subject of extensive research efforts. This is the key toward a possible transformation into devices of the exciting phenomena such as conductance modification or polarity observed at ferroelectric domain walls. The main methods currently available to determine the polarization characteristics in thin films suffer from being local, time demanding, potentially vitiated by artefacts, or even blinded in some cases. A nondestructive method based on resonant diffraction is proposed for the determination of the polarization orientation in multiferroic, ferroelectric, or pyroelectric thin films. The method is experimentally illustrated for multiferroic gallium ferrite thin films. Its validity is also theoretically shown for the perovskite‐based structure of the emblematic ferroelectric Pb(Zr,Ti)O3, which augurs numerous prospects for its potential applications.
Water models for biomolecular simulations
Authors: Onufriev Alexey V. , Izadi Saeed
Published: November 2017

Modern simulation and modeling approaches to investigation of biomolecular structure and function rely heavily on a variety of methods—water models—to approximate the influence of solvent. We give a brief overview of several distinct classes of available water models, with the emphasis on the conceptual basis at each level of approximation. The main focus is on classes of models most widely used in atomistic simulations, including popular implicit and explicit solvent models. Among the latter, nonpolarizable N‐point models are covered in most detail, including some recent methodological advances and nuances. Notes on practical availability and usage in biomolecular simulations are included. Atomistic simulations that were hardly possible only a short while ago have revealed significant problems that can be traced to deficiencies of most commonly used N‐point water models. Recently developed models of this class approximate experimental properties of liquid water much closer than before, and show promise in practical biomolecular simulations. Obstacles to wider adoption of these more accurate water models, both technical and conceptual, are discussed. It is argued that verifying robustness of simulation results to the choice of water model can be of immediate benefit even in the absence of a clear replacement for older models; a specific strategy is proposed. The review is concluded with a discussion on how force‐field development efforts can benefit from better solvent models, and vice versa. WIREs Comput Mol Sci 2018, 8:e1347. doi: 10.1002/wcms.1347

This article is categorized under:

Structure and Mechanism > Computational Biochemistry and Biophysics

Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods
From quarks to nucleons in dark matter direct detection
Authors: Bishara Fady , Brod Joachim , Grinstein Benjamin , Zupan Jure
Published: November 2017

Abstract

We provide expressions for the nonperturbative matching of the effective field theory describing dark matter interactions with quarks and gluons to the effective theory of nonrelativistic dark matter interacting with nonrelativistic nucleons. We give expressions of leading and subleading order in chiral counting. In general, a single partonic operator matches onto several nonrelativistic operators already at leading order in chiral counting. Keeping only one operator at the time in the nonrelativistic effective theory thus does not properly describe the scattering in direct detection. The matching of the axial-axial partonic level operator, as well as the matching of the operators coupling DM to the QCD anomaly term, include naively momentum suppressed terms. However, these are still of leading chiral order due to pion poles and can be numerically important.
R(D∗), |Vcb|, and the Heavy Quark Symmetry relations between form factors
Authors: Bigi Dante , Gambino Paolo , Schacht Stefan
Published: November 2017

Abstract

Stringent relations between the B
(∗) → D
(∗) form factors exist in the heavy quark limit and the leading symmetry breaking corrections are known. We reconsider their uncertainty and role in the analysis of recent Belle data for B → D
(∗)ℓν with model-independent parametrizations and in the related prediction of R(D
(∗)). We find |V

cb
| = 41.5(1.3) 10−3 and |V

cb
| = 40.6(
− 1.3
+ 1.2
) 10−3 using input from Light Cone Sum Rules, and R(D
∗) = 0.260(8).
A semantics comparison workbench for a concurrent, asynchronous, distributed programming language
Authors: Corrodi Claudio , Heußner Alexander , Poskitt Christopher M.
Published: November 2017

A number of high-level languages and libraries have been proposed that offer novel and simple to use abstractions for concurrent, asynchronous, and distributed programming. The execution models that realise them, however, often change over time—whether to improve performance, or to extend them to new language features—potentially affecting behavioural and safety properties of existing programs. This is exemplified by
Scoop
, a message-passing approach to concurrent object-oriented programming that has seen multiple changes proposed and implemented, with demonstrable consequences for an idiomatic usage of its core abstraction. We propose a
semantics comparison workbench
for
Scoop
with fully and semi-automatic tools for analysing and comparing the state spaces of programs with respect to different execution models or semantics. We demonstrate its use in checking the consistency of properties across semantics by applying it to a set of representative programs, and highlighting a deadlock-related discrepancy between the principal execution models of
Scoop
. Furthermore, we demonstrate the extensibility of the workbench by generalising the formalisation of an execution model to support recently proposed extensions for distributed programming. Our workbench is based on a modular and parameterisable graph transformation semantics implemented in the
Groove
tool. We discuss how graph transformations are leveraged to atomically model intricate language abstractions, how the visual yet algebraic nature of the model can be used to ascertain soundness, and highlight how the approach could be applied to similar languages.
Analysis of intergeneric sexual hybridization between transgenic Brassica oleracea and Sinapis alba
Authors: Li Jun , Zhang Chunlei , Guan Chunyun , Luo Lixia , Ren Li , Wei Wenhui , Lu Guangyuan , Fang Xiaoping
Published: November 2017

Sinapis alba possesses a number of desirable traits that can be employed to broaden genetic variability in Brassica oleracea or B. napus. Using transgenic B. oleracea (CC, 2n = 18) as paternal plants and non-transgenic S. alba (SS, 2n = 24) as maternal plants, 11 hybrid plants were successfully obtained by using a combination of ovary culture and embryo rescue, while 2 seedlings of the reciprocal cross were generated but lost during the propagation. The hybridity of these plants was confirmed by flower color and other agronomic characteristics, chromosome counting, and pollen viability. Most of the intergeneric F1 plants showed only one set each of S and C chromosome (SC, 2n = 21) and were male sterile, while a few plants were semi-fertile and had one set of S chromosomes but two sets of C chromosomes (CCS, 2n = 30). PCR, genomic Southern blotting and qRT-PCR for bar gene revealed that among the F1 hybrid plants only 9.1% was bar positive and could be forwarded to F2 and F3 generation. The majority of F3 plants obtained sufficient resistance to Alternaria brassicae. Thus, the generation of disease (A. brassicae) and herbicide (Bastar) resistant intergeneric hybrids was of importance for breeding program. The existence of bar gene in these intermediate materials will facilitate the identification of hybridity and transfer of S.alba traits into target genetic background.
Pre-residency publication and its association with paediatric residency match outcome—a retrospective analysis of a national database
Authors: Gupta Ronish , Norris Mark L. , Barrowman Nicholas , Writer Hilary
Published: November 2017

Introduction Scholarly activity is considered valuable in the resident selection process by candidates and program directors alike, despite existing literature suggesting applicants with scholarly work do not perform better in the match. These studies, however, are limited in that they have only measured whether candidates have successfully matched or not. To try and reconcile the existing disconnect in the value of pre-residency scholarly activity, we sought to deepen the understanding by investigating whether pre-residency publication is associated with a higher rank-order list match achievement.

Methods Anonymized data were collected from the Canadian Residency Matching Service for individuals matched to paediatric programs from 2007–2012. The primary analysis was to identify whether documentation of ≥1 pre-residency publication was associated with achieving a first-choice match. Secondary analyses included evaluating for an association between multiple pre-residency publications, academic presentations or a graduate degree and match outcome.

Results Of a total of 843 matched individuals, 406 (48.2%) listed ≥1 pre-residency publication and 494 (58.6%) matched to their first-choice program. The possession of ≥1 pre-residency publications was not associated with matching to a candidate’s first-choice program (odds ratio = 0.94 [95% confidence interval = 0.71–1.24], p = 0.66). Similarly, listing ≥2 publications, ≥3 publications, a graduate degree, or an academic presentation was not associated with achieving a first-choice match.

Conclusions The results provide increased support for the notion that in aggregate, candidate scholarly activity does not influence match outcome.
The Application of “The Judicial Trilemma” to the WTO Dispute Settlement System
Authors: Van Damme Isabelle
Published: November 2017

Dunoff and Pollack's timely article on The Judicial Trilemma offers a constructive paradigm through which to examine and assess the design and the behavior of international courts and tribunals and, in particular, their members at a time when, despite the increasing judicialization of international law and relations, the legitimacy and function of such courts and tribunals are being questioned in political and public discourse. The focus of this response is on the application of the paradigm to the World Trade Organization (WTO) dispute settlement system, which is one of the international courts and tribunals examined by the authors.
Bonhoeffer's Lutheran assertions: Cataphasis as teaching responsibility to the ‘other’
Authors: Sanchez Michelle C.
Published: November 2017

Structural similarities have been noted between Dietrich Bonhoeffer's account of ethical responsibility and more recent accounts advocated by philosophers who emphasise responsibility to alterity. Yet, there remains one stubborn difference between Bonhoeffer and these philosophers: his unequivocal embrace of strongly cataphatic speech. This raises the following question: it is possible for contemporary Christian ethicists and theologians to enlist Bonhoeffer in the aim of reconceiving an ethic of responsibility to the ‘other’ when Bonhoeffer himself relies on such concrete, exclusive language? This article will argue that attention to Martin Luther's defence of theological assertions provides a lens through which the performative force of Bonhoeffer's cataphatic language can be better understood as a particular and traditional use of language that teaches an ethical posture of epistemic humility.
Essence and fullness: Evaluating the creator–creature distinction in Jonathan Edwards
Authors: Salladin James
Published: November 2017

Soteriological participation in God, variously termed theosis, divinisation or deification commands widespread interest across the spectrum of Christian theology. A key difficulty is how to maintain the creator–creature distinction, while bridging it to gain intimacy. Jonathan Edwards provides a Reformed perspective on this conversation, by way of his distinction between the incommunicable divine essence and the communicable divine fullness. This article clarifies this distinction by evaluating its coherence and exploring whether it divorces God's immanent and economic life. It argues that distinguishing two forms of participation – methexis verses koinonia – clarifies coherence and shows that it does not divide God's being from act.
Sergii Bulgakov's ‘Sofiologiia smerti’
Authors: Smith T. Allan
Published: November 2017

This article examines S. Bulgakov's treatise ‘Sofiologiia smerti’ (‘Sophiology of Death’), which has been relatively neglected by scholars. Death is a topic that recurs with some frequency throughout Bulgakov's writings; that it merited its own study indicates the importance that he attached to the topic. The article provides a biographical, cultural and intellectual context for the treatise, as well some comments on its literary features. Bulgakov's use of sophiology and kenotic theology to explore the process of dying and the fact of death itself come under review. His reflections on human death and dying lead Bulgakov to explore how the Son of God experienced death and the involvement of the Trinity itself in that experience. Christ becomes fully human when he dies, and his death is the pattern for all human death.
MultiTANDEM
Authors: Messemaker Anne , Schall Arthur , Haberstroh Julia , Pantel Johannes
Published: November 2017

Abstract. The MultiTANDEM system trains management staff at outpatient nursing facilities to be TANDEM trainers (i.e., multiplicators for social-skills training) of professional and family caregivers for people with dementia. We used a pre-post-1-post-2 follow-up design to evaluate intervention and implementation success. Results showed a significant increase in the communication skills of caregivers and a significant reduction in family caregiver burden. Analyses of the implementation showed high acceptability among multiplicators and a high penetration of TANDEM trainings among their fellow staff members. An evaluation of the sustainability yielded heterogeneous results. Evaluation of impeding factors showed a reluctance among family caregivers to participate. Further studies with larger sample sizes and including all implementation outcomes are recommended.
Cell death and cell lysis are separable events during pyroptosis
Authors: DiPeso Lucian , Ji Daisy X , Vance Russell E , Price Jordan V
Published: November 2017

Although much insight has been gained into the mechanisms by which activation of the inflammasome can trigger pyroptosis in mammalian cells, the precise kinetics of the end stages of pyroptosis have not been well characterized. Using time-lapse fluorescent imaging to analyze the kinetics of pyroptosis in individual murine macrophages, we observed distinct stages of cell death and cell lysis. Our data demonstrate that cell membrane permeability resulting from gasdermin D pore formation is coincident with the cessation of cell movement, loss of mitochondrial activity, and cell swelling, events that can be uncoupled from cell lysis. We propose a model of pyroptosis in which cell death can occur independently of cell lysis. The uncoupling of cell death from cell lysis may allow for better control of cytosolic contents upon activation of the inflammasome.
Zinc-finger proteins in health and disease
Authors: Cassandri Matteo , Smirnov Artem , Novelli Flavia , Pitolli Consuelo , Agostini Massimiliano , Malewicz Michal , Melino Gerry , Raschellà Giuseppe
Published: November 2017

Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and have a wide range of molecular functions. Given the wide variety of zinc-finger domains, ZNFs are able to interact with DNA, RNA, PAR (poly-ADP-ribose) and other proteins. Thus, ZNFs are involved in the regulation of several cellular processes. In fact, ZNFs are implicated in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, cell migration, and numerous other processes. The aim of this review is to provide a comprehensive summary of the current state of knowledge of this class of proteins. Firstly, we describe the actual classification of ZNFs, their structure and functions. Secondly, we focus on the biological role of ZNFs in the development of organisms under normal physiological and pathological conditions.
Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis
Authors: Hu Dan , Notarbartolo Samuele , Croonenborghs Tom , Patel Bonny , Cialic Ron , Yang Tun-Hsiang , Aschenbrenner Dominik , Andersson Karin M. , Gattorno Marco , Pham Minh , Kivisakk Pia , Pierre Isabelle V. , Lee Youjin , Kiani Karun , Bokarewa Maria , Tjon Emily , Pochet Nathalie , Sallusto Federica , Kuchroo Vijay K. , Weiner Howard L.
Published: November 2017

We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+(TH1/17) and IFN-γ−IL-17+(TH17) CD4+T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 cells have elevated expression ofCXCR3and reduced expression ofIFNG,CCL3,CLL4,GZMB, andIL10compared to healthy controls. Moreover, higher expression ofIL10in TH17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory TH17 cells, which can be used to both identify pathogenic TH17 cells and to measure the effect of treatment on TH17 cells in human autoimmune diseases.
Photonic simulation of entanglement growth and engineering after a spin chain quench
Authors: Pitsios Ioannis , Banchi Leonardo , Rab Adil S. , Bentivegna Marco , Caprara Debora , Crespi Andrea , Spagnolo Nicolò , Bose Sougato , Mataloni Paolo , Osellame Roberto , Sciarrino Fabio
Published: November 2017

The time evolution of quantum many-body systems is one of the most important processes for benchmarking quantum simulators. The most curious feature of such dynamics is the growth of quantum entanglement to an amount proportional to the system size (volume law) even when interactions are local. This phenomenon has great ramifications for fundamental aspects, while its optimisation clearly has an impact on technology (e.g., for on-chip quantum networking). Here we use an integrated photonic chip with a circuit-based approach to simulate the dynamics of a spin chain and maximise the entanglement generation. The resulting entanglement is certified by constructing a second chip, which measures the entanglement between multiple distant pairs of simulated spins, as well as the block entanglement entropy. This is the first photonic simulation and optimisation of the extensive growth of entanglement in a spin chain, and opens up the use of photonic circuits for optimising quantum devices.
Author Correction: Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway
Authors: Morizawa Yosuke M. , Hirayama Yuri , Ohno Nobuhiko , Shibata Shinsuke , Shigetomi Eiji , Sui Yang , Nabekura Junichi , Sato Koichi , Okajima Fumikazu , Takebayashi Hirohide , Okano Hideyuki , Koizumi Schuichi
Published: November 2017

The original version of this Article contained an error in the spelling of the author Nobuhiko Ohno, which was incorrectly given as Noubuhiko Ohno. This has now been corrected in both the PDF and HTML versions of the Article.
Loss of HIF-1α in natural killer cells inhibits tumour growth by stimulating non-productive angiogenesis
Authors: Krzywinska Ewelina , Kantari-Mimoun Chahrazade , Kerdiles Yann , Sobecki Michal , Isagawa Takayuki , Gotthardt Dagmar , Castells Magali , Haubold Johannes , Millien Corinne , Viel Thomas , Tavitian Bertrand , Takeda Norihiko , Fandrey Joachim , Vivier Eric , Sexl Veronika , Stockmann Christian
Published: November 2017

Productive angiogenesis, a prerequisite for tumour growth, depends on the balanced release of angiogenic and angiostatic factors by different cell types within hypoxic tumours. Natural killer (NK) cells kill cancer cells and infiltrate hypoxic tumour areas. Cellular adaptation to low oxygen is mediated by Hypoxia-inducible factors (HIFs). We found that deletion of HIF-1α in NK cells inhibited tumour growth despite impaired tumour cell killing. Tumours developing in these conditions were characterised by a high-density network of immature vessels, severe haemorrhage, increased hypoxia, and facilitated metastasis due to non-productive angiogenesis. Loss of HIF-1α in NK cells increased the bioavailability of the major angiogenic cytokine vascular endothelial growth factor (VEGF) by decreasing the infiltration of NK cells that express angiostatic soluble VEGFR-1. In summary, this identifies the hypoxic response in NK cells as an inhibitor of VEGF-driven angiogenesis, yet, this promotes tumour growth by allowing the formation of functionally improved vessels.
Fast-forwarding of Hamiltonians and exponentially precise measurements
Authors: Atia Yosi , Aharonov Dorit
Published: November 2017

The time-energy uncertainty relation (TEUR) $$\Delta {\it{t}}\Delta {\it{E}}\,{\bf{ \ge }}\,{\textstyle{{\bf{1}} \over {\bf{2}}}}$$
Δ
t
Δ
E

≥

1

2

holds if the Hamiltonian is completely unknown, but can be violated otherwise; here we initiate a rigorous study describing when and to what extent such violations can occur. To this end, we propose a computational version of the TEUR (cTEUR), in which Δt is replaced by the computational complexity of simulating the measurement. cTEUR violations are proved to occur if and only if the Hamiltonian can be fast forwarded (FF), namely, simulated for time t with complexity significantly smaller than t. Shor’s algorithm provides an example of exponential cTEUR violations; we show that so do commuting local Hamiltonians and quadratic fermion Hamiltonians. A general FF method is ruled out, but finding further examples, as well as experimental demonstrations, are left for future work. We discuss possible connections to sensing and quantum gravity. This work initiates a rigorous theory of efficiency versus accuracy in energy measurements using computational complexity language.
Wiskott-Aldrich syndrome protein regulates autophagy and inflammasome activity in innate immune cells
Authors: Lee Pamela P. , Lobato-Márquez Damián , Pramanik Nayani , Sirianni Andrea , Daza-Cajigal Vanessa , Rivers Elizabeth , Cavazza Alessia , Bouma Gerben , Moulding Dale , Hultenby Kjell , Westerberg Lisa S. , Hollinshead Michael , Lau Yu-Lung , Burns Siobhan O. , Mostowy Serge , Bajaj-Elliott Mona , Thrasher Adrian J.
Published: November 2017

Dysregulation of autophagy and inflammasome activity contributes to the development of auto-inflammatory diseases. Emerging evidence highlights the importance of the actin cytoskeleton in modulating inflammatory responses. Here we show that deficiency of Wiskott–Aldrich syndrome protein (WASp), which signals to the actin cytoskeleton, modulates autophagy and inflammasome function. In a model of sterile inflammation utilizing TLR4 ligation followed by ATP or nigericin treatment, inflammasome activation is enhanced in monocytes from WAS patients and in WAS-knockout mouse dendritic cells. In ex vivo models of enteropathogenic Escherichia coli and Shigella flexneri infection, WASp deficiency causes defective bacterial clearance, excessive inflammasome activation and host cell death that are associated with dysregulated septin cage-like formation, impaired autophagic p62/LC3 recruitment and defective formation of canonical autophagosomes. Taken together, we propose that dysregulation of autophagy and inflammasome activities contribute to the autoinflammatory manifestations of WAS, thereby identifying potential targets for therapeutic intervention.
Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation
Authors: Davey Gabriela E. , Adhireksan Zenita , Ma Zhujun , Riedel Tina , Sharma Deepti , Padavattan Sivaraman , Rhodes Daniela , Ludwig Alexander , Sandin Sara , Murray Benjamin S. , Dyson Paul J. , Davey Curt A.
Published: November 2017

The ‘acidic patch’ is a highly electronegative cleft on the histone H2A–H2B dimer in the nucleosome. It is a fundamental motif for protein binding and chromatin dynamics, but the cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize a family of binuclear ruthenium compounds that selectively target the nucleosome acidic patch, generating intra-nucleosomal H2A-H2B cross-links as well as inter-nucleosomal cross-links. In contrast to cisplatin or the progenitor RAPTA-C anticancer drugs, the binuclear agents neither arrest specific cell cycle phases nor elicit DNA damage response, but rather induce an irreversible, anomalous state of condensed chromatin that ultimately results in apoptosis. In vitro, the compounds induce misfolding of chromatin fibre and block the binding of the regulator of chromatin condensation 1 (RCC1) acidic patch-binding protein. This family of chromatin-modifying molecules has potential for applications in drug development and as tools for chromatin research.
TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells
Authors: Saitoh Shin-Ichiroh , Abe Fumiko , Kanno Atsuo , Tanimura Natsuko , Mori Saitoh Yoshiko , Fukui Ryutaro , Shibata Takuma , Sato Katsuaki , Ichinohe Takeshi , Hayashi Mayumi , Kubota Kazuishi , Kozuka-Hata Hiroko , Oyama Masaaki , Kikko Yorifumi , Katada Toshiaki , Kontani Kenji , Miyake Kensuke
Published: November 2017

Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC–pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7+ lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7. The type I interferon signaling molecules TRAF3, IKKα, and mTORC1 are constitutively associated in pDCs. TLR7 localizes to mTORC1 and induces association of TRAF3 with the upstream molecule TRAF6. Finally, type I interferons are secreted in the vicinity of cell–cell contacts between clustered pDCs. These results suggest that TLR7 needs to move to the cell periphery to induce robust type I interferon responses in pDCs.
Capturing an initial intermediate during the P450nor enzymatic reaction using time-resolved XFEL crystallography and caged-substrate
Authors: Tosha Takehiko , Nomura Takashi , Nishida Takuma , Saeki Naoya , Okubayashi Kouta , Yamagiwa Raika , Sugahara Michihiro , Nakane Takanori , Yamashita Keitaro , Hirata Kunio , Ueno Go , Kimura Tetsunari , Hisano Tamao , Muramoto Kazumasa , Sawai Hitomi , Takeda Hanae , Mizohata Eiichi , Yamashita Ayumi , Kanematsu Yusuke , Takano Yu , Nango Eriko , Tanaka Rie , Nureki Osamu , Shoji Osami , Ikemoto Yuka , Murakami Hironori , Owada Shigeki , Tono Kensuke , Yabashi Makina , Yamamoto Masaki , Ago Hideo , Iwata So , Sugimoto Hiroshi , Shiro Yoshitsugu , Kubo Minoru
Published: November 2017

Time-resolved serial femtosecond crystallography using an X-ray free electron laser (XFEL) in conjunction with a photosensitive caged-compound offers a crystallographic method to track enzymatic reactions. Here we demonstrate the application of this method using fungal NO reductase, a heme-containing enzyme, at room temperature. Twenty milliseconds after caged-NO photolysis, we identify a NO-bound form of the enzyme, which is an initial intermediate with a slightly bent Fe-N-O coordination geometry at a resolution of 2.1 Å. The NO geometry is compatible with those analyzed by XFEL-based cryo-crystallography and QM/MM calculations, indicating that we obtain an intact Fe3+-NO coordination structure that is free of X-ray radiation damage. The slightly bent NO geometry is appropriate to prevent immediate NO dissociation and thus accept H− from NADH. The combination of using XFEL and a caged-compound is a powerful tool for determining functional enzyme structures during catalytic reactions at the atomic level.
The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile
Authors: Demmer Julius K. , Pal Chowdhury Nilanjan , Selmer Thorsten , Ermler Ulrich , Buckel Wolfgang
Published: November 2017

The electron transferring flavoprotein/butyryl-CoA dehydrogenase (EtfAB/Bcd) catalyzes the reduction of one crotonyl-CoA and two ferredoxins by two NADH within a flavin-based electron-bifurcating process. Here we report on the X-ray structure of the Clostridium difficile (EtfAB/Bcd)4 complex in the dehydrogenase-conducting D-state, α-FAD (bound to domain II of EtfA) and δ-FAD (bound to Bcd) being 8 Å apart. Superimposing Acidaminococcus fermentans EtfAB onto C. difficile EtfAB/Bcd reveals a rotation of domain II of nearly 80°. Further rotation by 10° brings EtfAB into the bifurcating B-state, α-FAD and β-FAD (bound to EtfB) being 14 Å apart. This dual binding mode of domain II, substantiated by mutational studies, resembles findings in non-bifurcating EtfAB/acyl-CoA dehydrogenase complexes. In our proposed mechanism, NADH reduces β-FAD, which bifurcates. One electron goes to ferredoxin and one to α-FAD, which swings over to reduce δ-FAD to the semiquinone. Repetition affords a second reduced ferredoxin and δ-FADH−, which reduces crotonyl-CoA.
Methanogenesis in oxygenated soils is a substantial fraction of wetland methane emissions
Authors: Angle Jordan C. , Morin Timothy H. , Solden Lindsey M. , Narrowe Adrienne B. , Smith Garrett J. , Borton Mikayla A. , Rey-Sanchez Camilo , Daly Rebecca A. , Mirfenderesgi Golnazalsdat , Hoyt David W. , Riley William J. , Miller Christopher S. , Bohrer Gil , Wrighton Kelly C.
Published: November 2017

The current paradigm, widely incorporated in soil biogeochemical models, is that microbial methanogenesis can only occur in anoxic habitats. In contrast, here we show clear geochemical and biological evidence for methane production in well-oxygenated soils of a freshwater wetland. A comparison of oxic to anoxic soils reveal up to ten times greater methane production and nine times more methanogenesis activity in oxygenated soils. Metagenomic and metatranscriptomic sequencing recover the first near-complete genomes for a novel methanogen species, and show acetoclastic production from this organism was the dominant methanogenesis pathway in oxygenated soils. This organism, Candidatus Methanothrix paradoxum, is prevalent across methane emitting ecosystems, suggesting a global significance. Moreover, in this wetland, we estimate that up to 80% of methane fluxes could be attributed to methanogenesis in oxygenated soils. Together, our findings challenge a widely held assumption about methanogenesis, with significant ramifications for global methane estimates and Earth system modeling.
Implications of improved representations of plant respiration in a changing climate
Authors: Huntingford Chris , Atkin Owen K. , Martinez-de la Torre Alberto , Mercado Lina M. , Heskel Mary A. , Harper Anna B. , Bloomfield Keith J. , O’Sullivan Odhran S. , Reich Peter B. , Wythers Kirk R. , Butler Ethan E. , Chen Ming , Griffin Kevin L. , Meir Patrick , Tjoelker Mark G. , Turnbull Matthew H. , Sitch Stephen , Wiltshire Andy , Malhi Yadvinder
Published: November 2017

Land-atmosphere exchanges influence atmospheric CO2. Emphasis has been on describing photosynthetic CO2 uptake, but less on respiration losses. New global datasets describe upper canopy dark respiration (Rd) and temperature dependencies. This allows characterisation of baseline Rd, instantaneous temperature responses and longer-term thermal acclimation effects. Here we show the global implications of these parameterisations with a global gridded land model. This model aggregates Rd to whole-plant respiration Rp, driven with meteorological forcings spanning uncertainty across climate change models. For pre-industrial estimates, new baseline Rd increases Rp and especially in the tropics. Compared to new baseline, revised instantaneous response decreases Rp for mid-latitudes, while acclimation lowers this for the tropics with increases elsewhere. Under global warming, new Rd estimates amplify modelled respiration increases, although partially lowered by acclimation. Future measurements will refine how Rd aggregates to whole-plant respiration. Our analysis suggests Rp could be around 30% higher than existing estimates.
TFEB regulates lysosomal positioning by modulating TMEM55B expression and JIP4 recruitment to lysosomes
Authors: Willett Rose , Martina José A. , Zewe James P. , Wills Rachel , Hammond Gerald R. V. , Puertollano Rosa
Published: November 2017

Lysosomal distribution is linked to the role of lysosomes in many cellular functions, including autophagosome degradation, cholesterol homeostasis, antigen presentation, and cell invasion. Alterations in lysosomal positioning contribute to different human pathologies, such as cancer, neurodegeneration, and lysosomal storage diseases. Here we report the identification of a novel mechanism of lysosomal trafficking regulation. We found that the lysosomal transmembrane protein TMEM55B recruits JIP4 to the lysosomal surface, inducing dynein-dependent transport of lysosomes toward the microtubules minus-end. TMEM55B overexpression causes lysosomes to collapse into the cell center, whereas depletion of either TMEM55B or JIP4 results in dispersion toward the cell periphery. TMEM55B levels are transcriptionally upregulated following TFEB and TFE3 activation by starvation or cholesterol-induced lysosomal stress. TMEM55B or JIP4 depletion abolishes starvation-induced retrograde lysosomal transport and prevents autophagosome–lysosome fusion. Overall our data suggest that the TFEB/TMEM55B/JIP4 pathway coordinates lysosome movement in response to a variety of stress conditions.
Chemical potential of quasi-equilibrium magnon gas driven by pure spin current
Authors: Demidov V. E. , Urazhdin S. , Divinskiy B. , Bessonov V. D. , Rinkevich A. B. , Ustinov V. V. , Demokritov S. O.
Published: November 2017

Pure spin currents provide the possibility to control the magnetization state of conducting and insulating magnetic materials. They allow one to increase or reduce the density of magnons, and achieve coherent dynamic states of magnetization reminiscent of the Bose–Einstein condensation. However, until now there was no direct evidence that the state of the magnon gas subjected to spin current can be treated thermodynamically. Here, we show experimentally that the spin current generated by the spin-Hall effect drives the magnon gas into a quasi-equilibrium state that can be described by the Bose–Einstein statistics. The magnon population function is characterized either by an increased effective chemical potential or by a reduced effective temperature, depending on the spin current polarization. In the former case, the chemical potential can closely approach, at large driving currents, the lowest-energy magnon state, indicating the possibility of spin current-driven Bose–Einstein condensation.
Non-canonical activation of OmpR drives acid and osmotic stress responses in single bacterial cells
Authors: Chakraborty Smarajit , Winardhi Ricksen S. , Morgan Leslie K. , Yan Jie , Kenney Linda J.
Published: November 2017

Unlike eukaryotes, bacteria undergo large changes in osmolality and cytoplasmic pH. It has been described that during acid stress, bacteria internal pH promptly acidifies, followed by recovery. Here, using pH imaging in single living cells, we show that following acid stress, bacteria maintain an acidic cytoplasm and the osmotic stress transcription factor OmpR is required for acidification. The activation of this response is non-canonical, involving a regulatory mechanism requiring the OmpR cognate kinase EnvZ, but not OmpR phosphorylation. Single cell analysis further identifies an intracellular pH threshold ~6.5. Acid stress reduces the internal pH below this threshold, increasing OmpR dimerization and DNA binding. During osmotic stress, the internal pH is above the threshold, triggering distinct OmpR-related pathways. Preventing intracellular acidification of Salmonella renders it avirulent, suggesting that acid stress pathways represent a potential therapeutic target. These results further emphasize the advantages of single cell analysis over studies of population averages.
Specific heat, Electrical resistivity and Electronic band structure properties of noncentrosymmetric Th7Fe3 superconductor
Authors: Tran V. H. , Sahakyan M.
Published: November 2017

Noncentrosymmetric superconductor Th7Fe3 has been investigated by means of specific heat, electrical resisitivity measurements and electronic properties calculations. Sudden drop in the resistivity at 2.05 ± 0.15 K and specific heat jump at 1.98 ± 0.02 K are observed, rendering the superconducting transition. A model of two BCS-type gaps appears to describe the zero-magnetic-field specific heat better than those based on the isotropic BCS theory or anisotropic functions. A positive curvature of the upper critical field H
c2(Tc) and nonlinear field dependence of the Sommerfeld coefficient at 0.4 K qualitatively support the two-gap scenario, which predicts Hc2(0) = 13 kOe. The theoretical densities of states and electronic band structures (EBS) around the Fermi energy show a mixture of Th 6d- and Fe 3d-electrons bands, being responsible for the superconductivity. Furthermore, the EBS and Fermi surfaces disclose significantly anisotropic splitting associated with asymmetric spin-orbit coupling (ASOC). The ASOC sets up also multiband structure, which presumably favours a multigap superconductivity. Electron Localization Function reveals the existence of both metallic and covalent bonds, the latter may have different strengths depending on the regions close to the Fe or Th atoms. The superconducting, electronic properties and implications of asymmetric spin-orbit coupling associated with noncentrosymmetric structure are discussed.
Ectopic FOXP3 Expression Preserves Primitive Features Of Human Hematopoietic Stem Cells While Impairing Functional T Cell Differentiation
Authors: Santoni de Sio F. R. , Passerini L. , Valente M. M. , Russo F. , Naldini L. , Roncarolo M. G. , Bacchetta R.
Published: November 2017

FOXP3 is the transcription factor ruling regulatory T cell function and maintenance of peripheral immune tolerance, and mutations in its coding gene causes IPEX autoimmune syndrome. FOXP3 is also a cell-cycle inhibitor and onco-suppressor in different cell types. In this work, we investigate the effect of ectopic FOXP3 expression on HSC differentiation and we challenged this approach as a possible HSC-based gene therapy for IPEX. FOXP3-expressing HSC showed reduced proliferation ability and increased maintenance of primitive markers in vitro in both liquid and OP9-ΔL1 co-cultures. When transplanted into immunodeficient mice, FOXP3-expressing HSC showed significantly enhanced engraftment ability. This was due to a pronounced increase in the frequency of repopulating cells, as assessed by extreme limiting dilution assay. Likely underlying the increased repopulating ability, FOXP3 expressing HSC showed significantly enhanced expression of genes controlling stemness features. However, peripheral T cells developed in the FOXP3-humanized mice were quantitatively reduced and hyporesponsive to cytokine and polyclonal stimulation. Our findings reveal unpredicted effects of FOXP3 in the biology of HSC and may provide new tools to manipulate primitive features in HSC for clinical applications. Moreover, they formally prove the need of preserving endogenous FOXP3 regulation for an HSC-based gene therapy approach for IPEX syndrome.
A molecular mechanism of symmetry breaking in the early chick embryo
Authors: Arias Clemente F. , Herrero Miguel A. , Stern Claudio D. , Bertocchini Federica
Published: November 2017

The first obvious sign of bilateral symmetry in mammalian and avian embryos is the appearance of the primitive streak in the future posterior region of a radially symmetric disc. The primitive streak marks the midline of the future embryo. The mechanisms responsible for positioning the primitive streak remain largely unknown. Here we combine experimental embryology and mathematical modelling to analyse the role of the TGFβ-related molecules BMP4 and Vg1/GDF1 in positioning the primitive streak. Bmp4 and Vg1 are first expressed throughout the embryo, and then become localised to the future anterior and posterior regions of the embryo, where they will, respectively, inhibit or induce formation of the primitive streak. We propose a model based on paracrine signalling to account for the separation of the two domains starting from a homogeneous array of cells, and thus for the topological transformation of a radially symmetric disc to a bilaterally symmetric embryo.
Severe Pollution in China Amplified by Atmospheric Moisture
Authors: Tie Xuexi , Huang Ru-Jin , Cao Junji , Zhang Qiang , Cheng Yafang , Su Hang , Chang Di , Pöschl Ulrich , Hoffmann Thorsten , Dusek Uli , Li Guohui , Worsnop Douglas R. , O’Dowd Colin D.
Published: November 2017

In recent years, severe haze events often occurred in China, causing serious environmental problems. The mechanisms responsible for the haze formation, however, are still not well understood, hindering the forecast and mitigation of haze pollution. Our study of the 2012–13 winter haze events in Beijing shows that atmospheric water vapour plays a critical role in enhancing the heavy haze events. Under weak solar radiation and stagnant moist meteorological conditions in winter, air pollutants and water vapour accumulate in a shallow planetary boundary layer (PBL). A positive feedback cycle is triggered resulting in the formation of heavy haze: (1) the dispersal of water vapour is constrained by the shallow PBL, leading to an increase in relative humidity (RH); (2) the high RH induces an increase of aerosol particle size by enhanced hygroscopic growth and multiphase reactions to increase particle size and mass, which results in (3) further dimming and decrease of PBL height, and thus further depressing of aerosol and water vapour in a very shallow PBL. This positive feedback constitutes a self-amplification mechanism in which water vapour leads to a trapping and massive increase of particulate matter in the near-surface air to which people are exposed with severe health hazards.