bluuebunny/crossref_metadata_2025 huggingface dataset:
Marine accident learning with fuzzy cognitive maps (MALFCMs) and Bayesian networks
Authors: de Maya Beatriz Navas , Babaleye Ahmed O. , Kurt Rafet E.
Published: October 2019

Addressing safety is considered a priority starting from the design stage of any vessel until end-of-life. However, despite all safety measures developed, accidents are still occurring. This is a consequence of the complex nature of shipping accidents where too many factors are involved including human factors. Therefore, there is a need for a practical method, which can identify the importance weightings for each contributing factor involved in accidents. As a result, by identifying the importance weightings for each factor, risk assessments can be informed, and risk control options can be developed and implemented more effectively. To this end, Marine Accident Learning with Fuzzy Cognitive Maps (MALFCM) approach incorporated with Bayesian networks (BNs) is suggested and applied in this study. The MALFCM approach is based on the concept and principles of fuzzy cognitive maps (FCMs) to represent the interrelations amongst accident contributor factors. Thus, MALFCM allows identifying the importance weightings for each factor involved in an accident, which can serve as prior failure probabilities within BNs. Hence, in this study, a specific accident will be investigated with the proposed MALFCM approach.
A new approach to PM extrusion
Authors: Nickels Liz
Published: October 2019

Automotive manufacturers want to make passenger vehicles cheaper, lighter, and more fuel-efficient. Researchers in the US have developed a one-stage powder extrusion process which could offer a solution with the aid of aluminum alloy powder.
The effects of geometry and heating rate on thermocapillary convection in the liquid bridge
Authors: Kang Qi , Wu Di , Duan Li , Hu Liang , Wang Jia , Zhang Pu , Hu Wenrui
Published: October 2019

The experimental study on thermocapillary convection in liquid bridges of large Prandtl number has been carried out on Tiangong-2 in space. The purpose of these experiments is to study the oscillation instability of thermocapillary convection, and to discover and recognize the mechanism of destabilization of thermocapillary convection in the microgravity environment in space. In this paper, the geometry of a half-floating-zone liquid bridge is featured by the aspect ratioArand volume ratioVr, and its influence on critical conditions of oscillatory thermocapillary convection is studied. More than 700 sets of space experiments have been finished. The critical conditions and oscillation characteristics of thermocapillary convection instability in theAr–Vrparameter space have been fully obtained under microgravity conditions for the first time. It is found that theAr–Vrparameter space can be divided into two regions of different critical conditions and oscillation characteristics: the region of low frequency oscillation, and the region of high frequency oscillation. More importantly, we obtain the complete configuration of these two stability neutral curves, and find that the low frequency mode is a ‘’ type curve. Based on this, we discuss the influence of heating rate on the oscillation mode. It is found that the heating rate affects the selection of critical mode, which results in a jump change of critical temperature difference. The findings of this study are helpful to better understand the critical modes and transition processes of thermocapillary convection in liquid bridges with different configurations.
Effects of rotation on the bulk turbulent convection
Authors: Toselli Francesco , Musacchio Stefano , Boffetta Guido
Published: October 2019

We study rotating homogeneous turbulent convection forced by a mean vertical temperature gradient by means of direct numerical simulations in the Boussinesq approximation in a rotating frame. In the absence of rotation, our results are in agreement with the ‘ultimate regime of thermal convection’ for the scaling of the Nusselt and Reynolds numbers versus Rayleigh and Prandtl numbers. Rotation is found to increase both $Nu$ and $Re$ at fixed $Ra$ with a maximum enhancement for intermediate values of the Rossby numbers, qualitatively similar, but with stronger intensity, to what is observed in Rayleigh–Bénard rotating convection. Our results are interpreted in terms of a quasi-bidimensionalization of the flow with the formation of columnar structures displaying strong correlation between the temperature and the vertical velocity fields.
Enhanced Iron Flux to Antarctic Sea Ice via Dust Deposition From Ice‐Free Coastal Areas
Authors: Duprat L. , Kanna N. , Janssens J. , Roukaerts A. , Deman F. , Townsend A. T. , Meiners K. M. , van der Merwe P. , Lannuzel D.
Published: October 2019

Antarctic sea ice is an important temporal reservoir of iron which can boost primary production in the marginal ice zone during the seasonal melt. While studies have reported that Antarctic fast ice bears high concentrations of iron due to the proximity to coastal sources, less clear are the biogeochemical changes this iron pool undergoes during late spring. Here we describe a 3‐week time series of physical and biogeochemical data, including iron, from first‐year coastal fast ice sampled near Davis Station (Prydz Bay, East Antarctica) during late austral spring 2015. Our study shows that dissolved and particulate iron concentrations in sea ice were up to two orders of magnitude higher than in under‐ice seawater. Furthermore, our results indicate a significant contribution of lithogenic iron from the Vestfold Hills (as deduced from the comparison with crustal element ratios) to the particulate iron pool in fast ice after a blizzard event halfway through the time series. Windblown dust represented approximately 75% of the particulate iron found in the ice and is a potential candidate for keeping concentrations of soluble iron stable during our observations. These results suggest that iron entrapped during ice formation, likely from sediments, as well as local input of coastal dust, supports primary productivity in Davis fast ice. As ice‐free land areas are likely to expand over the course of the century, this work highlights the need to quantify iron inputs from continental Antarctic dust and its bioavailability for ice algae and phytoplankton.
Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
Authors: Balli Martina , Vitali Francesca , Janiszewski Adrian , Caluwé Ellen , Cortés-Calabuig Alvaro , Carpentier Sebastien , Duelen Robin , Ronzoni Flavio , Marcelis Lukas , Bosisio Francesca Maria , Bellazzi Riccardo , Luttun Aernout , De Angelis Maria G. Cusella , Ceccarelli Gabriele , Lluis Frederic , Sampaolesi Maurilio
Published: October 2019

Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which AMG exhibits its beneficial effects remains unrevealed. Herein we show that AMG improves skin re-epithelialization by accelerating the migration of fibroblasts and keratinocytes. More specifically, AMG-treated wounds showed improvement of indispensable events associated with successful wound healing such as granulation tissue formation, organized collagen content, and newly formed blood vessels. We demonstrate that AMG is enriched with a pool of WH-associated growth factors that may provide the starting signal for a faster endogenous wound healing response. This work links the increased cell migration rate to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, which is followed by an increase in matrix metalloproteinase expression and their extracellular enzymatic activity. Overall we reveal the AMG-mediated wound healing transcriptional signature and shed light on the AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process. In this way, we present a framework for future improvements in AMG therapy for skin tissue regeneration applications.
Leishmania donovani parasite requires Atg8 protein for infectivity and survival under stress
Authors: Giri Sagnik , Shaha Chandrima
Published: October 2019

The importance of autophagy in parasites with a digenetic life cycle like Leishmania spp. is significant. The parasite survives as promastigotes in the insect gut and as immotile amastigotes in mammals. This study demonstrates increased autophagy in Leishmania parasite during progression of in vitro life cycle and upon exposure to stress stimuli like starvation, oxidative stress, and drugs. Autophagy inhibition during stress exposure increased cell death, indicating the importance of autophagy in cellular defense against adverse conditions. Atg8 protein, a homolog of mammalian autophagy protein LC3 is expressed in Leishmania parasite but its function remains unknown. Overexpression of Atg8 (Atg8-OE) rendered the parasites resistant to stress and capable of infecting macrophages in substantial numbers; however, disruption of the Atg8 gene (ΔAtg8) resulting in suppression of Atg8 protein expression, increased susceptibility to stress and reduced the capability to cause infection. A critical event in the Leishmania parasite lifecycle is the differentiation of promastigote forms to the disease causing amastigote forms. The failure of ΔAtg8 parasites lacking Atg8 protein to differentiate into amastigotes, unlike the Atg8-OE and vector-transfected parasites, clearly indicated Atg8 involvement in a crucial event. The inability of ΔAtg8 parasites to infect macrophages in vitro was verified in an in vivo mouse model of leishmaniases where infection could not be induced by the ΔAtg8 parasites. Autophagy is known to be involved in the remodeling of damaged organelles. The accumulation of Atg8 around damaged mitochondria suggested increase of autophagy in the vicinity of the organelle. This buildup was prevented when mitochondria generated reactive oxygen species that were quenched, suggesting them as possible signaling molecules for sensing mitochondrial instability. In summary, our study provides new evidences for a crucial role of Atg8 protein in sustaining Leishmania parasite survival during life cycle and stress exposure, differentiation to amastigotes, and their infective abilities.
Severe head dysgenesis resulting from imbalance between anterior and posterior ontogenetic programs
Authors: Grall Emmanuelle , Gourain Victor , Naïr Asmaa , Martin Elisabeth , Birling Marie-Christine , Freund Jean-Noël , Duluc Isabelle
Published: October 2019

Head dysgenesis is a major cause of fetal demise and craniofacial malformation. Although mutations in genes of the head ontogenetic program have been reported, many cases remain unexplained. Head dysgenesis has also been related to trisomy or amplification of the chromosomal region overlapping the CDX2 homeobox gene, a master element of the trunk ontogenetic program. Hence, we investigated the repercussion on head morphogenesis of the imbalance between the head and trunk ontogenetic programs, by means of ectopic rostral expression of CDX2 at gastrulation. This caused severe malformations affecting the forebrain and optic structures, and also the frontonasal process associated with defects in neural crest cells colonization. These malformations are the result of the downregulation of genes of the head program together with the abnormal induction of trunk program genes. Together, these data indicate that the imbalance between the anterior and posterior ontogenetic programs in embryos is a new possible cause of head dysgenesis during human development, linked to defects in setting up anterior neuroectodermal structures.
Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis
Authors: Godet Inês , Shin Yu Jung , Ju Julia A. , Ye I Chae , Wang Guannan , Gilkes Daniele M.
Published: October 2019

Hypoxia is known to be detrimental in cancer and contributes to its development. In this work, we present an approach to fate-map hypoxic cells in vivo in order to determine their cellular response to physiological O2 gradients as well as to quantify their contribution to metastatic spread. We demonstrate the ability of the system to fate-map hypoxic cells in 2D, and in 3D spheroids and organoids. We identify distinct gene expression patterns in cells that experienced intratumoral hypoxia in vivo compared to cells exposed to hypoxia in vitro. The intratumoral hypoxia gene-signature is a better prognostic indicator for distant metastasis-free survival. Post-hypoxic tumor cells have an ROS-resistant phenotype that provides a survival advantage in the bloodstream and promotes their ability to establish overt metastasis. Post-hypoxic cells retain an increase in the expression of a subset of hypoxia-inducible genes at the metastatic site, suggesting the possibility of a ‘hypoxic memory.’
Climate-induced phenology shifts linked to range expansions in species with multiple reproductive cycles per year
Authors: Macgregor Callum J. , Thomas Chris D. , Roy David B. , Beaumont Mark A. , Bell James R. , Brereton Tom , Bridle Jon R. , Dytham Calvin , Fox Richard , Gotthard Karl , Hoffmann Ary A. , Martin Geoff , Middlebrook Ian , Nylin Sӧren , Platts Philip J. , Rasteiro Rita , Saccheri Ilik J. , Villoutreix Romain , Wheat Christopher W. , Hill Jane K.
Published: October 2019

Advances in phenology (the annual timing of species’ life-cycles) in response to climate change are generally viewed as bioindicators of climate change, but have not been considered as predictors of range expansions. Here, we show that phenology advances combine with the number of reproductive cycles per year (voltinism) to shape abundance and distribution trends in 130 species of British Lepidoptera, in response to ~0.5 °C spring-temperature warming between 1995 and 2014. Early adult emergence in warm years resulted in increased within- and between-year population growth for species with multiple reproductive cycles per year (n = 39 multivoltine species). By contrast, early emergence had neutral or negative consequences for species with a single annual reproductive cycle (n = 91 univoltine species), depending on habitat specialisation. We conclude that phenology advances facilitate polewards range expansions in species exhibiting plasticity for both phenology and voltinism, but may inhibit expansion by less flexible species.
Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis
Authors: Gallagher C. S. , Mäkinen N. , Harris H. R. , Rahmioglu N. , Uimari O. , Cook J. P. , Shigesi N. , Ferreira T. , Velez-Edwards D. R. , Edwards T. L. , Mortlock S. , Ruhioglu Z. , Day F. , Becker C. M. , Karhunen V. , Martikainen H. , Järvelin M.-R. , Cantor R. M. , Ridker P. M. , Terry K. L. , Buring J. E. , Gordon S. D. , Medland S. E. , Montgomery G. W. , Nyholt D. R. , Hinds D. A. , Tung J. Y. ,   the 23andMe Research Team, Agee Michelle , Alipanahi Babak , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McIntyre Matthew H. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A. M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Vacic Vladimir , Wilson Catherine H. , Perry J. R. B. , Lind P. A. , Painter J. N. , Martin N. G. , Morris A. P. , Chasman D. I. , Missmer S. A. , Zondervan K. T. , Morton C. C.
Published: October 2019

Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10−8) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
Ultrafast growth of nanocrystalline graphene films by quenching and grain-size-dependent strength and bandgap opening
Authors: Zhao Tong , Xu Chuan , Ma Wei , Liu Zhibo , Zhou Tianya , Liu Zhen , Feng Shun , Zhu Mengjian , Kang Ning , Sun Dong-Ming , Cheng Hui-Ming , Ren Wencai
Published: October 2019

Nanocrystallization is a well-known strategy to dramatically tune the properties of materials; however, the grain-size effect of graphene at the nanometer scale remains unknown experimentally because of the lack of nanocrystalline samples. Here we report an ultrafast growth of graphene films within a few seconds by quenching a hot metal foil in liquid carbon source. Using Pt foil and ethanol as examples, four kinds of nanocrystalline graphene films with average grain size of ~3.6, 5.8, 8.0, and 10.3 nm are synthesized. It is found that the effect of grain boundary becomes more pronounced at the nanometer scale. In comparison with pristine graphene, the 3.6 nm-grained film retains high strength (101 GPa) and Young’s modulus (576 GPa), whereas the electrical conductivity is declined by over 100 times, showing semiconducting behavior with a bandgap of ~50 meV. This liquid-phase precursor quenching method opens possibilities for ultrafast synthesis of typical graphene materials and other two-dimensional nanocrystalline materials.
Longitudinal ridges imparted by high-speed granular flow mechanisms in martian landslides
Authors: Magnarini Giulia , Mitchell Thomas M. , Grindrod Peter M. , Goren Liran , Schmitt Harrison H.
Published: October 2019

The presence of longitudinal ridges documented in long runout landslides across our solar system is commonly associated with the existence of a basal layer of ice. However, their development, the link between their occurrence and the emplacement mechanisms of long runout landslides, and the necessity of a basal ice layer remain poorly understood. Here, we analyse the morphometry of longitudinal ridges of a martian landslide and show that the wavelength of the ridges is 2–3 times the average thickness of the landslide deposit, a unique scaling relationship previously reported in ice-free rapid granular flow experiments. We recognize en-echelon features that we interpret as kinematic indicators, congruent with experimentally-measured transverse velocity gradient. We suggest that longitudinal ridges should not be considered as unequivocal evidence for presence of ice, rather as inevitable features of rapid granular sliding material, that originate from a mechanical instability once a kinematic threshold is surpassed.
Phase separation-deficient TDP43 remains functional in splicing
Authors: Schmidt Hermann Broder , Barreau Ariana , Rohatgi Rajat
Published: October 2019

Intrinsically disordered regions (IDRs) are often fast-evolving protein domains of low sequence complexity that can drive phase transitions and are commonly found in many proteins associated with neurodegenerative diseases, including the RNA processing factor TDP43. Yet, how phase separation contributes to the physiological functions of TDP43 in cells remains enigmatic. Here, we combine systematic mutagenesis guided by evolutionary sequence analysis with a live-cell reporter assay of TDP43 phase dynamics to identify regularly-spaced hydrophobic motifs separated by flexible, hydrophilic segments in the IDR as a key determinant of TDP43 phase properties. This heuristic framework allows customization of the material properties of TDP43 condensates to determine effects on splicing function. Remarkably, even a mutant that fails to phase-separate at physiological concentrations can still efficiently mediate the splicing of a quantitative, single-cell splicing reporter and endogenous targets. This suggests that the ability of TDP43 to phase-separate is not essential for its splicing function.
Critical dependence of morphodynamic models of fluvial and tidal systems on empirical downslope sediment transport
Authors: Baar A. W. , Boechat Albernaz M. , van Dijk W. M. , Kleinhans M. G.
Published: October 2019

The morphological development of fluvial and tidal systems is forecast more and more frequently by models in scientific and engineering studies for decision making regarding climate change mitigation, flood control, navigation and engineering works. However, many existing morphodynamic models predict unrealistically high channel incision, which is often dampened by increased gravity-driven sediment transport on side-slopes by up to two orders of magnitude too high. Here we show that such arbitrary calibrations dramatically bias sediment dynamics, channel patterns, and rate of morphological change. For five different models bracketing a range of scales and environments, we found that it is impossible to calibrate a model on both sediment transport magnitude and morphology. Consequently, present calibration practice may cause an order magnitude error in either morphology or morphological change. We show how model design can be optimized for different applications. We discuss the major implications for model interpretation and a critical knowledge gap.
Unraveling the thermodynamic criteria for size-dependent spontaneous phase separation in soft porous crystals
Authors: Rogge Sven M. J. , Waroquier Michel , Van Speybroeck Veronique
Published: October 2019

Soft porous crystals (SPCs) harbor a great potential as functional nanoporous materials owing to their stimuli-induced and tuneable morphing between different crystalline phases. These large-amplitude phase transitions are often assumed to occur cooperatively throughout the whole material, which thereby retains its perfect crystalline order. Here, we disprove this paradigm through mesoscale first-principles based molecular dynamics simulations, demonstrating that morphological transitions do induce spatial disorder under the form of interfacial defects and give rise to yet unidentified phase coexistence within a given sample. We hypothesize that this phase coexistence can be stabilized by carefully tuning the experimental control variables through, e.g., temperature or pressure quenching. The observed spatial disorder helps to rationalize yet elusive phenomena in SPCs, such as the impact of crystal downsizing on their flexible nature, thereby identifying the crystal size as a crucial design parameter for stimuli-responsive devices based on SPC nanoparticles and thin films.
Random auxetics from buckling fibre networks
Authors: Domaschke S. , Morel A. , Fortunato G. , Ehret A. E.
Published: October 2019

Auxetic materials have gained increasing interest in the last decades, fostered by auspicious applications in various fields. While the design of new auxetics has largely focused on meta-materials with deterministic, periodically arranged structures, we show here by theoretical and numerical analysis that pronounced auxetic behaviour with negative Poisson’s ratios of very large magnitude can occur in random fibre networks with slender, reasonably straight fibre segments that buckle and deflect. We further demonstrate in experiments that such auxetic fibre networks, which increase their thickness by an order of magnitude and more than quintuple their volume when moderately extended, can be produced by electrospinning. Our results thus augment the class of auxetics by a large group of straightforwardly fabricable meta-materials with stochastic microstructure.
A domino reaction for generating β-aryl aldehydes from alkynes by substrate recognition catalysis
Authors: Fang Weiwei , Bauer Felix , Dong Yaxi , Breit Bernhard
Published: October 2019

The development of universal catalyst systems that enable efficient, selective, and straightforward chemical transformations is of immense scientific importance. Here we develop a domino process comprising three consecutive reaction steps based on the strategy of supramolecular substrate recognition. This approach provides valuable β-aryl aldehydes from readily accessible α-alkynoic acids and arenes under mild reaction conditions, employing a supramolecular Rh catalyst containing an acylguanidine-bearing phosphine ligand. Furthermore, the synthesis of a key intermediate of Avitriptan using this protocol is accomplished. The first step of the reaction sequence is proved to be the regioselective hydroformylation of α-alkynoic acids. Remarkably, molecular recognition of the ligand and the substrate via hydrogen bonding plays a key role in this step. Control experiments indicate that the reaction further proceeds via 1,4-addition of an arene nucleophile to the unsaturated aldehyde intermediate and subsequent decarboxylation.
Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy
Authors: Huang Liping , Li Yanan , Du Yunai , Zhang Yiyi , Wang Xiuxia , Ding Yuan , Yang Xiangliang , Meng Fanling , Tu Jiasheng , Luo Liang , Sun Chunmeng
Published: October 2019

One of the main challenges for immune checkpoint blockade antibodies lies in malignancies with limited T-cell responses or immunologically “cold” tumors. Inspired by the capability of fever-like heat in inducing an immune-favorable tumor microenvironment, mild photothermal therapy (PTT) is proposed to sensitize tumors to immune checkpoint inhibition and turn “cold” tumors “hot.” Here we present a combined all-in-one and all-in-control strategy to realize a local symbiotic mild photothermal-assisted immunotherapy (SMPAI). We load both a near-infrared (NIR) photothermal agent IR820 and a programmed death-ligand 1 antibody (aPD-L1) into a lipid gel depot with a favorable property of thermally reversible gel-to-sol phase transition. Manually controlled NIR irradiation regulates the release of aPD-L1 and, more importantly, increases the recruitment of tumor-infiltrating lymphocytes and boosts T-cell activity against tumors. In vivo antitumor studies on 4T1 and B16F10 models demonstrate that SMPAI is an effective and promising strategy for treating “cold” tumors.
Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology
Authors: Sonner Jana K. , Keil Melanie , Falk-Paulsen Maren , Mishra Neha , Rehman Ateequr , Kramer Magdalena , Deumelandt Katrin , Röwe Julian , Sanghvi Khwab , Wolf Lara , von Landenberg Anna , Wolff Hendrik , Bharti Richa , Oezen Iris , Lanz Tobias V. , Wanke Florian , Tang Yilang , Brandao Ines , Mohapatra Soumya R. , Epping Lisa , Grill Alexandra , Röth Ralph , Niesler Beate , Meuth Sven G. , Opitz Christiane A. , Okun Jürgen G. , Reinhardt Christoph , Kurschus Florian C. , Wick Wolfgang , Bode Helge B. , Rosenstiel Philip , Platten Michael
Published: October 2019

The interaction between the mammalian host and its resident gut microbiota is known to license adaptive immune responses. Nutritional constituents strongly influence composition and functional properties of the intestinal microbial communities. Here, we report that omission of a single essential amino acid - tryptophan – from the diet abrogates CNS autoimmunity in a mouse model of multiple sclerosis. Dietary tryptophan restriction results in impaired encephalitogenic T cell responses and is accompanied by a mild intestinal inflammatory response and a profound phenotypic shift of gut microbiota. Protective effects of dietary tryptophan restriction are abrogated in germ-free mice, but are independent of canonical host sensors of intracellular tryptophan metabolites. We conclude that dietary tryptophan restriction alters metabolic properties of gut microbiota, which in turn have an impact on encephalitogenic T cell responses. This link between gut microbiota, dietary tryptophan and adaptive immunity may help to develop therapeutic strategies for protection from autoimmune neuroinflammation.
Structural transitions during the scaffolding-driven assembly of a viral capsid
Authors: Ignatiou Athanasios , Brasilès Sandrine , El Sadek Fadel Mehdi , Bürger Jörg , Mielke Thorsten , Topf Maya , Tavares Paulo , Orlova Elena V.
Published: October 2019

Assembly of tailed bacteriophages and herpesviruses starts with formation of procapsids (virion precursors without DNA). Scaffolding proteins (SP) drive assembly by chaperoning the major capsid protein (MCP) to build an icosahedral lattice. Here we report near-atomic resolution cryo-EM structures of the bacteriophage SPP1 procapsid, the intermediate expanded procapsid with partially released SPs, and the mature capsid with DNA. In the intermediate state, SPs are bound only to MCP pentons and to adjacent subunits from hexons. SP departure results in the expanded state associated with unfolding of the MCP N-terminus and straightening of E-loops. The newly formed extensive inter-capsomere bonding appears to compensate for release of SPs that clasp MCP capsomeres together. Subsequent DNA packaging instigates bending of MCP A domain loops outwards, closing the hexons central opening and creating the capsid auxiliary protein binding interface. These findings provide a molecular basis for the sequential structural rearrangements during viral capsid maturation.
Orbitofrontal signals for two-component choice options comply with indifference curves of Revealed Preference Theory
Authors: Pastor-Bernier Alexandre , Stasiak Arkadiusz , Schultz Wolfram
Published: October 2019

Economic choice options contain multiple components and constitute vectorial bundles. The question arises how they are represented by single-dimensional, scalar neuronal signals that are suitable for economic decision-making. Revealed Preference Theory provides formalisms for establishing preference relations between such bundles, including convenient graphic indifference curves. During stochastic choice between bundles with the same two juice components, we identified neuronal signals for vectorial, multi-component bundles in the orbitofrontal cortex of monkeys. A scalar signal integrated the values from all bundle components in the structured manner of the Theory; it followed the behavioral indifference curves within their confidence limits, was indistinguishable between differently composed but equally revealed preferred bundles, predicted bundle choice and complied with an optimality axiom. Further, distinct signals in other neurons coded the option components separately but followed indifference curves as a population. These data demonstrate how scalar signals represent vectorial, multi-component choice options.
Reverberant 3D optical coherence elastography maps the elasticity of individual corneal layers
Authors: Zvietcovich Fernando , Pongchalee Pornthep , Meemon Panomsak , Rolland Jannick P. , Parker Kevin J.
Published: October 2019

The elasticity mapping of individual layers in the cornea using non-destructive elastography techniques advances diagnosis and monitoring of ocular diseases and treatments in ophthalmology. However, transient Lamb waves, currently used in most dynamic optical coherence and ultrasound elastography techniques, diminish the translation of wave speed into shear/Young’s modulus. Here, we present reverberant 3D optical coherence elastography (Rev3D-OCE), a novel approach leveraging the physical properties of diffuse fields in detecting elasticity gradients not only in the lateral direction, but also along the depth axis of the cornea. A Monte Carlo analysis, finite element simulations, and experiments in layered phantoms are conducted to validate the technique and to characterize the axial elastography resolution. Experiments in ex vivo porcine cornea at different intraocular pressures reveal that Rev3D-OCE enables the elastic characterization of single layers that matches the anatomical description of corneal layers with unprecedented contrast in the dynamic OCE field.
NSD2 overexpression drives clustered chromatin and transcriptional changes in a subset of insulated domains
Authors: Lhoumaud Priscillia , Badri Sana , Rodriguez-Hernaez Javier , Sakellaropoulos Theodore , Sethia Gunjan , Kloetgen Andreas , Cornwell MacIntosh , Bhattacharyya Sourya , Ay Ferhat , Bonneau Richard , Tsirigos Aristotelis , Skok Jane A.
Published: October 2019

CTCF and cohesin play a key role in organizing chromatin into topologically associating domain (TAD) structures. Disruption of a single CTCF binding site is sufficient to change chromosomal interactions leading to alterations in chromatin modifications and gene regulation. However, the extent to which alterations in chromatin modifications can disrupt 3D chromosome organization leading to transcriptional changes is unknown. In multiple myeloma, a 4;14 translocation induces overexpression of the histone methyltransferase, NSD2, resulting in expansion of H3K36me2 and shrinkage of antagonistic H3K27me3 domains. Using isogenic cell lines producing high and low levels of NSD2, here we find oncogene activation is linked to alterations in H3K27ac and CTCF within H3K36me2 enriched chromatin. A logistic regression model reveals that differentially expressed genes are significantly enriched within the same insulated domain as altered H3K27ac and CTCF peaks. These results identify a bidirectional relationship between 2D chromatin and 3D genome organization in gene regulation.
Ultrabroadband 3D invisibility with fast-light cloaks
Authors: Tsakmakidis K. L. , Reshef O. , Almpanis E. , Zouros G. P. , Mohammadi E. , Saadat D. , Sohrabi F. , Fahimi-Kashani N. , Etezadi D. , Boyd R. W. , Altug H.
Published: October 2019

An invisibility cloak should completely hide an object from an observer, ideally across the visible spectrum and for all angles of incidence and polarizations of light, in three dimensions. However, until now, all such devices have been limited to either small bandwidths or have disregarded the phase of the impinging wave or worked only along specific directions. Here, we show that these seemingly fundamental restrictions can be lifted by using cloaks made of fast-light media, termed tachyonic cloaks, where the wave group velocity is larger than the speed of light in vacuum. On the basis of exact analytic calculations and full-wave causal simulations, we demonstrate three-dimensional cloaking that cannot be detected even interferometrically across the entire visible regime. Our results open the road for ultrabroadband invisibility of large objects, with direct implications for stealth and information technology, non-disturbing sensors, near-field scanning optical microscopy imaging, and superluminal propagation.
A vertical silicon-graphene-germanium transistor
Authors: Liu Chi , Ma Wei , Chen Maolin , Ren Wencai , Sun Dongming
Published: October 2019

Graphene-base transistors have been proposed for high-frequency applications because of the negligible base transit time induced by the atomic thickness of graphene. However, generally used tunnel emitters suffer from high emitter potential-barrier-height which limits the transistor performance towards terahertz operation. To overcome this issue, a graphene-base heterojunction transistor has been proposed theoretically where the graphene base is sandwiched by silicon layers. Here we demonstrate a vertical silicon-graphene-germanium transistor where a Schottky emitter constructed by single-crystal silicon and single-layer graphene is achieved. Such Schottky emitter shows a current of 692 A cm−2and a capacitance of 41 nF cm−2, and thus the alpha cut-off frequency of the transistor is expected to increase from about 1 MHz by using the previous tunnel emitters to above 1 GHz by using the current Schottky emitter. With further engineering, the semiconductor-graphene-semiconductor transistor is expected to be one of the most promising devices for ultra-high frequency operation.
Regulation of the ER stress response by a mitochondrial microprotein
Authors: Chu Qian , Martinez Thomas F. , Novak Sammy Weiser , Donaldson Cynthia J. , Tan Dan , Vaughan Joan M. , Chang Tina , Diedrich Jolene K. , Andrade Leo , Kim Andrew , Zhang Tong , Manor Uri , Saghatelian Alan
Published: October 2019

Cellular homeostasis relies on having dedicated and coordinated responses to a variety of stresses. The accumulation of unfolded proteins in the endoplasmic reticulum (ER) is a common stress that triggers a conserved pathway called the unfolded protein response (UPR) that mitigates damage, and dysregulation of UPR underlies several debilitating diseases. Here, we discover that a previously uncharacterized 54-amino acid microprotein PIGBOS regulates UPR. PIGBOS localizes to the mitochondrial outer membrane where it interacts with the ER protein CLCC1 at ER–mitochondria contact sites. Functional studies reveal that the loss of PIGBOS leads to heightened UPR and increased cell death. The characterization of PIGBOS reveals an undiscovered role for a mitochondrial protein, in this case a microprotein, in the regulation of UPR originating in the ER. This study demonstrates microproteins to be an unappreciated class of genes that are critical for inter-organelle communication, homeostasis, and cell survival.
Dormant pathogenic CD4+ T cells are prevalent in the peripheral repertoire of healthy mice
Authors: Cebula Anna , Kuczma Michal , Szurek Edyta , Pietrzak Maciej , Savage Natasha , Elhefnawy Wessam R. , Rempala Grzegorz , Kraj Piotr , Ignatowicz Leszek
Published: October 2019

Thymic central tolerance eliminates most immature T cells with autoreactive T cell receptors (TCR) that recognize self MHC/peptide complexes. Regardless, an unknown number of autoreactive CD4+Foxp3− T cells escape negative selection and in the periphery require continuous suppression by CD4+Foxp3+ regulatory cells (Tregs). Here, we compare immune repertoires of Treg-deficient and Treg-sufficient mice to find Tregs continuously constraining one-third of mature CD4+Foxp3− cells from converting to pathogenic effectors in healthy mice. These dormant pathogenic clones frequently express TCRs activatable by ubiquitous autoantigens presented by class II MHCs on conventional dendritic cells, including self-peptides that select them in the thymus. Our data thus suggest that identification of most potentially autoreactive CD4+ T cells in the peripheral repertoire is critical to harness or redirect these cells for therapeutic advantage.
de Haas-van Alphen effect of correlated Dirac states in kagome metal Fe3Sn2
Authors: Ye Linda , Chan Mun K. , McDonald Ross D. , Graf David , Kang Mingu , Liu Junwei , Suzuki Takehito , Comin Riccardo , Fu Liang , Checkelsky Joseph G.
Published: October 2019

Primarily considered a medium of geometric frustration, there has been a growing recognition of the kagome network as a harbor of lattice-borne topological electronic phases. In this study we report the observation of magnetoquantum de Haas-van Alphen oscillations of the ferromagnetic kagome lattice metal Fe3Sn2. We observe a pair of quasi-two-dimensional Fermi surfaces arising from bulk massive Dirac states and show that these band areas and effective masses are systematically modulated by the rotation of the ferromagnetic moment. Combined with measurements of Berry curvature induced Hall conductivity, our observations suggest that the ferromagnetic Dirac fermions in Fe3Sn2 are subject to intrinsic spin-orbit coupling in the d electron sector which is likely of Kane-Mele type. Our results provide insights for spintronic manipulation of magnetic topological electronic states and pathways to realizing further highly correlated topological materials from the lattice perspective.
A secreted metal-binding protein protects necrotrophic phytopathogens from reactive oxygen species
Authors: Liu Lulu , Gueguen-Chaignon Virginie , Gonçalves Isabelle R , Rascle Christine , Rigault Martine , Dellagi Alia , Loisel Elise , Poussereau Nathalie , Rodrigue Agnès , Terradot Laurent , Condemine Guy
Published: October 2019

Few secreted proteins involved in plant infection common to necrotrophic bacteria, fungi and oomycetes have been identified except for plant cell wall-degrading enzymes. Here we study a family of iron-binding proteins that is present in Gram-negative and Gram-positive bacteria, fungi, oomycetes and some animals. Homolog proteins in the phytopathogenic bacterium Dickeya dadantii (IbpS) and the fungal necrotroph Botrytis cinerea (BcIbp) are involved in plant infection. IbpS is secreted, can bind iron and copper, and protects the bacteria against H2O2-induced death. Its 1.7 Å crystal structure reveals a classical Venus Fly trap fold that forms dimers in solution and in the crystal. We propose that secreted Ibp proteins binds exogenous metals and thus limit intracellular metal accumulation and ROS formation in the microorganisms.
Genome-wide microhomologies enable precise template-free editing of biologically relevant deletion mutations
Authors: Grajcarek Janin , Monlong Jean , Nishinaka-Arai Yoko , Nakamura Michiko , Nagai Miki , Matsuo Shiori , Lougheed David , Sakurai Hidetoshi , Saito Megumu K. , Bourque Guillaume , Woltjen Knut
Published: October 2019

The functional effect of a gene edit by designer nucleases depends on the DNA repair outcome at the targeted locus. While non-homologous end joining (NHEJ) repair results in various mutations, microhomology-mediated end joining (MMEJ) creates precise deletions based on the alignment of flanking microhomologies (µHs). Recently, the sequence context surrounding nuclease-induced double strand breaks (DSBs) has been shown to predict repair outcomes, for which µH plays an important role. Here, we survey naturally occurring human deletion variants and identify that 11 million or 57% are flanked by µHs, covering 88% of protein-coding genes. These biologically relevant mutations are candidates for precise creation in a template-free manner by MMEJ repair. Using CRISPR-Cas9 in human induced pluripotent stem cells (hiPSCs), we efficiently create pathogenic deletion mutations for demonstrable disease models with both gain- and loss-of-function phenotypes. We anticipate this dataset and gene editing strategy to enable functional genetic studies and drug screening.
Fouling-resistant biofilter of an anaerobic electrochemical membrane reactor
Authors: Yu Qilin , Zhang Yaobin
Published: October 2019

Membrane fouling is a considerable challenge for the stable operation of anaerobic membrane-based bioreactors. Membrane used as a cathode is a common measure to retard fouling growth in anaerobic electrochemical membrane bioreactors (AnEMBR), which; however, cannot avoid the fouling growth. Here we report a strategy using the membrane as an anode to resist membrane fouling in an AnEMBR. Although aggravating in the initial stage, the fouling on the anode membrane is gradually alleviated by the anode oxidation with enriching exoelectrogens to finally achieve a dynamic equilibrium between fouling growth and decomposition to maintain the operation stable. A mesh-like biofilter layer composed of cells with less extracellular polymeric substance (EPS) is formed on the membrane surface to lower the trans-membrane pressure and promote the interception of the anode membrane. The membrane has high electron storage and transfer capacities to accelerate the oxidation of the intercepted fouling materials, especially, the redundant EPSs of the biofilter layer.
Bacterial MgrB peptide activates chemoreceptor Fpr3 in mouse accessory olfactory system and drives avoidance behaviour
Authors: Bufe Bernd , Teuchert Yannick , Schmid Andreas , Pyrski Martina , Pérez-Gómez Anabel , Eisenbeis Janina , Timm Thomas , Ishii Tomohiro , Lochnit Günter , Bischoff Markus , Mombaerts Peter , Leinders-Zufall Trese , Zufall Frank
Published: October 2019

Innate immune chemoreceptors of the formyl peptide receptor (Fpr) family are expressed by vomeronasal sensory neurons (VSNs) in the accessory olfactory system. Their biological function and coding mechanisms remain unknown. We show that mouse Fpr3 (Fpr-rs1) recognizes the core peptide motif f-MKKFRW that is predominantly present in the signal sequence of the bacterial protein MgrB, a highly conserved regulator of virulence and antibiotic resistance in Enterobacteriaceae. MgrB peptide can be produced and secreted by bacteria, and is selectively recognized by a subset of VSNs. Exposure to the peptide also stimulates VSNs in freely behaving mice and drives innate avoidance. Our data shows that Fpr3 is required for neuronal detection and avoidance of peptides derived from a conserved master virulence regulator of enteric bacteria.
Late-stage trifluoromethylthiolation of benzylic C-H bonds
Authors: Xu Wentao , Wang Wenliang , Liu Tao , Xie Jin , Zhu Chengjian
Published: October 2019

The benzylic positions in drugs are sites that readily react with cytochrome P450 oxidases via single-electron oxidation. New synthetic methodologies to incorporate a fluoroalkyl group at the benzylic site are continually being developed, and in this paper, we report a metal-free and site-selective organophotoredox-catalyzed trifluoromethylthiolation of benzylic C-H bonds for a wide variety of alkyl arenes and heteroarenes. The precise and predictive regioselectivity among various C(sp3)-H bonds originates from an inner-sphere benzylic radical initiation mechanism, and avoids the use of external oxidants or hydrogen atom abstractors. Its practicality stems from the trifluoromethylthiolation of a series of drugs and complex organic molecules, which is overwhelmingly selective for benzyl groups. This operationally simple protocol can provide a general and practical access to structurally diverse benzylic trifluoromethyl sulfides produced from ubiquitous benzylic C-H bonds. Large scale trifluoromethylthiolation can be achieved with continuous flow photoredox technology.
Nuclear calcium signatures are associated with root development
Authors: Leitão Nuno , Dangeville Pierre , Carter Ross , Charpentier Myriam
Published: October 2019

In plants, nuclear Ca2+ releases are essential to the establishment of nitrogen-fixing and phosphate-delivering arbuscular mycorrhizal endosymbioses. In the legume Medicago truncatula, these nuclear Ca2+ signals are generated by a complex of nuclear membrane-localised ion channels including the DOES NOT MAKE INFECTIONS 1 (DMI1) and the cyclic nucleotide-gated channels (CNGC) 15s. DMI1 and CNCG15s are conserved among land plants, suggesting roles for nuclear Ca2+ signalling that extend beyond symbioses. Here we show that nuclear Ca2+ signalling initiates in the nucleus of Arabidopsis root cells and that these signals are correlated with primary root development, including meristem development and auxin homeostasis. In addition, we demonstrate that altering genetically AtDMI1 is sufficient to modulate the nuclear Ca2+ signatures, and primary root development. This finding supports the postulate that stimulus-specific information can be encoded in the frequency and duration of a Ca2+ signal and thereby regulate cellular function.