bluuebunny/crossref_metadata_2025 huggingface dataset:
Quasi‐Static Granular Flow of Ice Mélange
Authors: Amundson J. M. , Burton J. C.
Published: September 2018

We use Landsat 8 imagery to generate ice mélange velocity fields at Greenland's three most productive outlet glaciers: Jakobshavn Isbræ, Helheim Glacier, and Kangerdlugssuaq Glacier. Winter velocity fields are generally steady and highly uniform. Summer velocity fields, on the other hand, tend to be much more variable and can be uniform, compressional, or extensional. We rarely observe compressional flow at Jakobshavn Isbræ or extensional flow at Helheim Glacier, while both are observed at Kangerdlugssuaq Glacier. Transverse velocity profiles from all three locations are suggestive of viscoplastic flow, in which deformation occurs primarily in shear zones along the fjord walls. We analyze the transverse profiles in the context of quasi‐static flow using continuum rheologies for granular materials and find that the force per unit width that ice mélange exerts on glacier termini increases exponentially with the ice mélange length‐to‐width ratio and the effective coefficient at the fjord walls. Our estimates of ice mélange resistance are consistent with other independent estimates and suggest that ice mélange may be capable of inhibiting iceberg calving events, especially during winter. Moreover, our results provide geophysical‐scale support for constitutive relationships for granular materials and suggest a potential avenue for modeling ice mélange dynamics with continuum models.
Estimating Modern Elevations of Pliocene Shorelines Using a Coupled Ice Sheet‐Earth‐Sea Level Model
Authors: Pollard D. , Gomez N. , DeConto R. M. , Han H. K.
Published: September 2018

A coupled ice sheet‐Earth‐sea level model is used to estimate the modern elevations of shoreline features that were formed at high sea level stands during the warm mid Pliocene ~3 million years ago. Knowledge of global mean sea level during this period is important as an indicator of possible future ice sheet retreat and sea level rise. However, local shoreline elevations can deviate from the eustatic mean by various geologic processes over the last 3 million years, including glacial isostatic adjustment of the solid Earth and gravitational field due to both Pliocene ice‐cover changes and more recent glacial cycles. Our coupled model includes glacial isostatic adjustment processes and simulates Antarctic ice sheet, global sea level, and solid Earth variations in the warmest mid‐Pliocene and over the last 40,000 years. Global maps of estimated modern elevations of Pliocene shoreline markers are produced for a standard radial profile of Earth viscosity and lithospheric thickness. Results are compared to an earlier study with an uncoupled Earth‐sea level model and a different methodology (Raymo et al., Nature Geoscience, 2011, https://doi.org:/10.1038/ngeo1118). As in that study, Pliocene shoreline elevations diverge significantly from the eustatic value in widespread regions, especially in the vicinity of present and former ice sheets. In some other regions, elevations are close to eustatic. The results emphasize that care should be taken in interpreting elevations of paleo‐shoreline markers.
Chronic myeloid leukaemia cells require the bone morphogenic protein pathway for cell cycle progression and self-renewal
Authors: Toofan Parto , Busch Caroline , Morrison Heather , O’Brien Stephen , Jørgensen Heather , Copland Mhairi , Wheadon Helen
Published: September 2018

Leukaemic stem cell (LSC) persistence remains a major obstacle to curing chronic myeloid leukaemia (CML). The bone morphogenic protein (BMP) pathway is deregulated in CML, with altered expression and response to the BMP ligands shown to impact on LSC expansion and behaviour. In this study, we determined whether alterations in the BMP pathway gene signature had any predictive value for therapeutic response by profiling 60 CML samples at diagnosis from the UK SPIRIT2 trial and correlating the data to treatment response using the 18-month follow-up data. There was significant deregulation of several genes involved in the BMP pathway with ACV1C, INHBA, SMAD7, SNAIL1 and SMURF2 showing differential expression in relation to response. Therapeutic targeting of CML cells using BMP receptor inhibitors, in combination with tyrosine kinase inhibitor (TKI), indicate a synergistic mode of action. Furthermore, dual treatment resulted in altered cell cycle gene transcription and irreversible cell cycle arrest, along with increased apoptosis compared to single agents. Targeting CML CD34+ cells with BMP receptor inhibitors resulted in fewer cell divisions, reduced numbers of CD34+ cells and colony formation when compared to normal donor CD34+ cells, both in the presence and absence of BMP4. In an induced pluripotent stem cell (iPSC) model generated from CD34+ hematopoietic cells, we demonstrate altered cell cycle profiles and dynamics of ALK expression in CML-iPSCs in the presence and absence of BMP4 stimulation, when compared to normal iPSC. Moreover, dual targeting with TKI and BMP inhibitor prevented the self-renewal of CML-iPSC and increased meso-endodermal differentiation. These findings indicate that transformed stem cells may be more reliant on BMP signalling than normal stem cells. These changes offer a therapeutic window in CML, with intervention using BMP inhibitors in combination with TKI having the potential to target LSC self-renewal and improve long-term outcome for patients.
Ectopic hTERT expression facilitates reprograming of fibroblasts derived from patients with Werner syndrome as a WS cellular model
Authors: Wang Shuyan , Liu Zhongfeng , Ye Yanxia , Li Bingnan , Liu Tiantian , Zhang Weiqi , Liu Guang-Hui , Zhang Y. Alex , Qu Jing , Xu Dawei , Chen Zhiguo
Published: September 2018

The induced pluripotent stem cell (iPSC) technology has provided a unique opportunity to develop disease-specific models and personalized treatment for genetic disorders, and is well suitable for the study of Werner syndrome (WS), an autosomal recessive disease with adult onset of premature aging caused by mutations in the RecQ like helicase (WRN) gene. WS-derived fibroblasts were previously shown to be able to generate iPSCs; however, it remains elusive how WS-derived iPSCs behave and whether they are able to mimic the disease-specific phenotype. The present study was designed to address these issues. Unexpectedly, we found that a specific WS fibroblast line of homozygous truncation mutation was difficult to be reprogrammed by using the Yamanaka factors even under hypoxic conditions due to their defect in induction of hTERT, the catalytic unit of telomerase. Ectopic expression of hTERT restores the ability of this WS fibroblast line to form iPSCs, although with a low efficiency. To examine the phenotype of WRN-deficient pluripotent stem cells, we also generated WRN knockout human embryonic stem (ES) cells by using the CRISPR/Cas9 method. The iPSCs derived from WS-hTERT cells and WRN-/- ESCs are fully pluripotent, express pluripotent markers and can differentiate into three germ layer cells; however, WS-iPSCs and WRN-/- ESCs show S phase defect in cell cycle progression. Moreover, WS-iPSCs and WRN-/- ESCs, like WS patient-derived fibroblasts, remain hypersensitive to topoisomerase inhibitors. Collectively, WS-derived iPSCs and WRN-/- ESCs mimic the intrinsic disease phenotype, which may serve as a suitable disease model, whereas not be good for a therapeutic purpose without gene correction.
Generating inner ear organoids containing putative cochlear hair cells from human pluripotent stem cells
Authors: Jeong Minjin , O’Reilly Molly , Kirkwood Nerissa K. , Al-Aama Jumana , Lako Majlinda , Kros Corné J. , Armstrong Lyle
Published: September 2018

In view of the prevalence of sensorineural hearing defects in an ageing population, the development of protocols to generate cochlear hair cells and their associated sensory neurons as tools to further our understanding of inner ear development are highly desirable. We report herein a robust protocol for the generation of both vestibular and cochlear hair cells from human pluripotent stem cells which represents an advance over currently available methods that have been reported to generate vestibular hair cells only. Generating otic organoids from human pluripotent stem cells using a three-dimensional culture system, we show formation of both types of sensory hair cells bearing stereociliary bundles with active mechano-sensory ion channels. These cells share many morphological characteristics with their in vivo counterparts during embryonic development of the cochlear and vestibular organs and moreover demonstrate electrophysiological activity detected through single-cell patch clamping. Collectively these data represent an advance in our ability to generate cells of an otic lineage and will be useful for building models of the sensory regions of the cochlea and vestibule.
EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway
Authors: Zhang Jing , Mo Hui-Qin , Tian Fu-Ju , Zeng Wei-Hong , Liu Xiao-Rui , Ma Xiao-Ling , Li Xiao , Qin Shi , Fan Cui-Fang , Lin Yi
Published: September 2018

Trophoblast dysfunction is one mechanism implicated in the etiology of recurrent miscarriage (RM). Regulation of trophoblast function, however, is complex and the mechanisms contributing to dysregulation remain to be elucidated. Herein, we found EIF5A1 expression levels to be significantly decreased in cytotrophoblasts in RM villous tissues compared with healthy controls. Using the HTR-8/SVneo cell line as a model system, we found that overexpression of EIF5A1 promotes trophoblast proliferation, migration and invasion in vitro. Knockdown of EIF5A1 or inhibiting its hypusination with N1-guanyl-1,7-diaminoheptane (GC7) suppresses these activities. Similarly, mutating EIF5A1 to EIF5A1K50A to prevent hypusination abolishes its effects on proliferation, migration and invasion. Furthermore, upregulation of EIF5A1 increases the outgrowth of trophoblasts in a villous explant culture model, whereas knockdown has the opposite effect. Suppression of EIF5A1 hypusination also inhibits the outgrowth of trophoblasts in explants. Mechanistically, ARAF mediates the regulation of trophoblast migration and invasion by EIF5A1. Hypusinated EIF5A1 regulates the integrin/ERK signaling pathway via controlling the translation of ARAF. ARAF level is also downregulated in trophoblasts of RM villous tissues and expression of ARAF is positively correlated with EIF5A1. Together, our results suggest that EIF5A1 may be a regulator of trophoblast function at the maternal–fetal interface and low levels of EIF5A1 and ARAF may be associated with RM.
Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis
Authors: Sun Li , Wang Qianqian , Chen Bin , Zhao Yuanyuan , Shen Bo , Wang Hua , Xu Jing , Zhu Miaolin , Zhao Xiangdong , Xu Changgen , Chen Zhihong , Wang Mei , Xu Wenrong , Zhu Wei
Published: September 2018

The expression of PD-L1 in tumor cells is one of the main causes of tumor immune escape. However, the exact mechanism for regulating PD-L1 expression in gastric cancer (GC) cells remains unclear. Our previous studies have shown that mesenchymal stem cells (MSCs) exert broad immunosuppressive potential, modulating the activity of cells either in innate or adaptive immune system to promote tumor progress. This study aims to investigate whether GCMSCs regulate the PD-L1 expression in GC cells and explore the specific molecular mechanism. The results have shown that GCMSCs enhanced PD-L1 expression in GC cells resulting in the resistance of GC cells to CD8+ T cells cytotoxicity. However, this resistance was attenuated with IL-8 inhibition. Further studies proved that IL-8 derived from GCMSCs induced PD-L1 expression in GC cells via c-Myc regulated by STAT3 and mTOR signaling pathways. Our data indicated that blocking IL-8 derived from GCMSCs may overcome the immune escape induced by PD-L1 in GC cells and provide a potential strategy to enhance the immunotherapy efficiency in GC.
3D micro-environment regulates NF-κβ dependent adhesion to induce monocyte differentiation
Authors: Bhattacharya Anindita , Agarwal Mahesh , Mukherjee Rachita , Sen Prosenjit , Sinha Deepak Kumar
Published: September 2018

Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signaling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.
MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis by disrupting Atg12
Authors: Lian Wei-Shiung , Ko Jih-Yang , Wu Re-Weng , Sun Yi-Chih , Chen Yu-Shan , Wu Shin-Long , Weng Lin-Hsiu , Jahr Holger , Wang Feng-Sheng
Published: September 2018

Chondrocyte loss is a prominent feature of osteoarthritis (OA). Autophagy is indispensable in maintaining the metabolic activities of cells exposed to deleterious stress. The contribution of microRNA signaling to chondrocyte autophagy in OA development remains elusive. We uncovered an association between poor autophagy and increased miR-128a expressions in articular chondrocytes of patients with end-stage knee OA and in a rat anterior cruciate ligament transection (ACLT) model for OA development. Cartilage matrix degradation and severe OA histopathology was evident upon forced miR-128a expression within the articular compartment. Intra-articular injections with miR-128a antisense oligonucleotide stabilized chondrocyte autophagy and slowed ACLT-mediated articular tissue destruction, including cartilage erosion, synovitis, osteophyte formation, and subchondral plate damage. In vitro, miR-128 signaling hindered Atg12 expression, LC3-II conversion, and autophagic puncta formation through targeting the 3′-untranslated region of Atg12. It increased apoptotic programs, diminishing cartilage formation capacity of articular chondrocytes. Inactivating histone methyltransferase EZH2 reduced methyl histone H3K27 enrichment in the miR-128a promoter and upregulated miR-128a transcription in inflamed chondrocytes. Taken together, miR-128a-induced Atg12 loss repressed chondrocyte autophagy to aggravate OA progression. EZH2 inactivation caused H3K27 hypomethylation to accelerate miR-128a actions. Interruption of miR-128a signaling attenuated chondrocyte dysfunction and delayed OA development. Our data provide new insights into how miR-128a signaling affects chondrocyte survival and articular cartilage anabolism and highlight the potential of miR-128a targeting therapy to alleviate knee OA.
A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines
Authors: Peris Leticia , Bisbal Mariano , Martinez-Hernandez José , Saoudi Yasmina , Jonckheere Julie , Rolland Marta , Sebastien Muriel , Brocard Jacques , Denarier Eric , Bosc Christophe , Guerin Christophe , Gory-Fauré Sylvie , Deloulme Jean Christophe , Lanté Fabien , Arnal Isabelle , Buisson Alain , Goldberg Yves , Blanchoin Laurent , Delphin Christian , Andrieux Annie
Published: September 2018

Emerging evidence indicates that microtubule-associated proteins (MAPs) are implicated in synaptic function; in particular, mice deficient for MAP6 exhibit striking deficits in plasticity and cognition. How MAP6 connects to plasticity mechanisms is unclear. Here, we address the possible role of this protein in dendritic spines. We find that in MAP6-deficient cortical and hippocampal neurons, maintenance of mature spines is impaired, and can be restored by expressing a stretch of the MAP6 sequence called Mc modules. Mc modules directly bind actin filaments and mediate activity-dependent stabilisation of F-actin in dendritic spines, a key event of synaptic plasticity. In vitro, Mc modules enhance actin filament nucleation and promote the formation of stable, highly ordered filament bundles. Activity-induced phosphorylation of MAP6 likely controls its transfer to the spine cytoskeleton. These results provide a molecular explanation for the role of MAP6 in cognition, enlightening the connection between cytoskeletal dysfunction, synaptic impairment and neuropsychiatric illnesses.
High niche diversity in Mesozoic pollinating lacewings
Authors: Liu Qing , Lu Xiumei , Zhang Qingqing , Chen Jun , Zheng Xiaoting , Zhang Weiwei , Liu Xingyue , Wang Bo
Published: September 2018

Niche diversity of pollinating insects plays a vital role in maintaining extant terrestrial ecosystems. A key dimension of pollination niches refers to the insect proboscis length that commonly matches the floral tube length. Here we describe new kalligrammatid lacewings (an iconic Mesozoic pollinating insect lineage) from late Cretaceous Burmese amber and Mesozoic sediments in China. Kalligrammatids display complex configurations of elongate mouthpart elements consisting of well-developed maxillae, labium and their palps. The mouthpart lengths vary among species, from 0.6 to 18.0 mm, suggesting corresponding variability in the floral tube lengths of Mesozoic plants. With the diversification of pollinating habits, the kalligrammatids presented highly divergent traits related to chemical communication and defence mechanisms. Together with other Mesozoic long-proboscid insects, these fossils not only reveal the high niche diversity of Mesozoic pollinating insects but also highlight the diversity of Mesozoic pollinator-dependent plants prior to the rise of angiosperms.
Energy cost of entanglement extraction in complex quantum systems
Authors: Bény Cédric , Chubb Christopher T. , Farrelly Terry , Osborne Tobias J.
Published: September 2018

What is the energy cost of extracting entanglement from complex quantum systems? Operationally, we may wish to actually extract entanglement. Conceptually, we may wish to physically understand the entanglement distribution as a function of energy. This is important, especially for quantum field theory vacua, which are extremely entangled. Here we build a theory to understand the energy cost of entanglement extraction. First, we consider a toy model, and then we define the entanglement temperature, relating energy cost to extracted entanglement. Next, we give a physical argument quantifying the energy cost of entanglement extraction in some quantum field vacua. There the energy cost depends on the spatial dimension: in one dimension, for example, it grows exponentially with extracted entanglement. Next, we provide approaches to bound the energy cost of extracting entanglement more generally. Finally, we look at spin chain models numerically to calculate the entanglement temperature using matrix product states.
Three-dimensional X-ray diffraction imaging of dislocations in polycrystalline metals under tensile loading
Authors: Cherukara Mathew J. , Pokharel Reeju , O’Leary Timothy S. , Baldwin J. Kevin , Maxey Evan , Cha Wonsuk , Maser Jorg , Harder Ross J. , Fensin Saryu J. , Sandberg Richard L.
Published: September 2018

The nucleation and propagation of dislocations is an ubiquitous process that accompanies the plastic deformation of materials. Consequently, following the first visualization of dislocations over 50 years ago with the advent of the first transmission electron microscopes, significant effort has been invested in tailoring material response through defect engineering and control. To accomplish this more effectively, the ability to identify and characterize defect structure and strain following external stimulus is vital. Here, using X-ray Bragg coherent diffraction imaging, we describe the first direct 3D X-ray imaging of the strain field surrounding a line defect within a grain of free-standing nanocrystalline material following tensile loading. By integrating the observed 3D structure into an atomistic model, we show that the measured strain field corresponds to a screw dislocation.
The shape of watersheds
Authors: Sassolas-Serrayet Timothée , Cattin Rodolphe , Ferry Matthieu
Published: September 2018

Since the 1950s river networks have been intensely researched in geosciences and hydrology. This led to the definition of scaling laws that described the organisation of landscapes under fluvial incision and were later explored by statistical physics and fractal mathematics. The emblematic Hack’s Law proposes a power-law relationship between watershed area and main stream length. Though extensively documented, a wide range of values is still reported for Hack’s parameters. Some authors associate this dispersion to local geologic and climatic conditions. Here based on the analysis of large sets of river basins in various climatic and geological settings, we confirm the geometric similarity of river networks. We demonstrate that basin shape is mostly related to Hack’s coefficient and not to the exponent, independently of external forcing such as lithology and pluviometry.
Evidence for dynamic kagome ice
Authors: Lhotel E. , Petit S. , Ciomaga Hatnean M. , Ollivier J. , Mutka H. , Ressouche E. , Lees M. R. , Balakrishnan G.
Published: September 2018

The search for two-dimensional quantum spin liquids, exotic magnetic states remaining disordered down to zero temperature, has been a great challenge in frustrated magnetism over the last few decades. Recently, evidence for fractionalized excitations, called spinons, emerging from these states has been observed in kagome and triangular antiferromagnets. In contrast, quantum ferromagnetic spin liquids in two dimensions, namely quantum kagome ices, have been less investigated, yet their classical counterparts exhibit amazing properties, magnetic monopole crystals as well as magnetic fragmentation. Here, we show that applying a magnetic field to the pyrochlore oxide Nd2Zr2O7, which has been shown to develop three-dimensional quantum magnetic fragmentation in zero field, results in a dimensional reduction, creating a dynamic kagome ice state: the spin excitation spectrum determined by neutron scattering encompasses a flat mode with a six arm shape akin to the kagome ice structure factor, from which dispersive branches emerge.
Ring synthetic chromosome V SCRaMbLE
Authors: Wang Juan , Xie Ze-Xiong , Ma Yuan , Chen Xiang-Rong , Huang Yao-Qing , He Bo , Bin Jia  , Li Bing-Zhi , Yuan Ying-Jin
Published: September 2018

Structural variations (SVs) exert important functional impacts on biological phenotypic diversity. Here we show a ring synthetic yeast chromosome V (ring_synV) can be used to continuously generate complex genomic variations and improve the production of prodeoxyviolacein (PDV) by applying Synthetic Chromosome Recombination and Modification by LoxP-mediated Evolution (SCRaMbLE) in haploid yeast cells. The SCRaMbLE of ring_synV generates aneuploid yeast strains with increased PDV productivity, and we identify aneuploid chromosome I, III, VI, XII, XIII, and ring_synV. The neochromosome of SCRaMbLEd ring_synV generated more unbalanced forms of variations, including duplication, insertions, and balanced forms of translocations and inversions than its linear form. Furthermore, of the 29 novel SVs detected, 11 prompted the PDV biosynthesis; and the deletion of uncharacterized gene YER182W is related to the improvement of the PDV. Overall, the SCRaMbLEing ring_synV embraces the evolution of the genome by modifying the chromosome number, structure, and organization, identifying targets for phenotypic comprehension.
Multi-terrane structure controls the contrasting lithospheric evolution beneath the western and central–eastern Tibetan plateau
Authors: Huangfu Pengpeng , Li Zhong-Hai , Gerya Taras , Fan Weiming , Zhang Kai-Jun , Zhang Huai , Shi Yaolin
Published: September 2018

The Tibetan plateau is manifested by contrasting along-strike lithospheric structures, but its formation mechanism and the relationship with the heterogeneous multi-terrane configuration is a challenging problem. Here we conduct systematic numerical modeling to explore the roles of width, density, and rheological properties of the multiple terranes in the lithospheric evolution of the Tibetan plateau, which reveals two distinct collision modes. In Mode-I, the lithospheric mantles of both the strong and weak terranes in the Tibetan plate are completely detached, followed by the underthrusting of Indian lithosphere beneath the whole plateau. Alternatively, Mode-II is characterized by full detachment of the weak terranes, but (partial) residue of the strong terranes during collision. These two contrasting modes, broadly consistent with the lithospheric structures of western and central–eastern Tibetan plateau, respectively, are strongly dependent on the along-strike variation of the width of the strong Lhasa–Qiangtang terranes.
Author Correction: TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells
Authors: Elster Dana , Tollot Marie , Schlegelmilch Karin , Ori Alessandro , Rosenwald Andreas , Sahai Erik , von Eyss Björn
Published: September 2018

In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include the following: “This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001144), the UK Medical Research Council (FC001144), and the Wellcome Trust (FC001144).”https://doi.org/10.1038/s41467-018-05370-7.
Concyclic CH-π arrays for single-axis rotations of a bowl in a tube
Authors: Matsuno Taisuke , Fujita Masahiro , Fukunaga Kengo , Sato Sota , Isobe Hiroyuki
Published: September 2018

The hydrogen bond is undoubtedly one of the most important non-covalent interactions. Among the several types of the hydrogen bonds, the CH–π interaction is a relatively new notion that is being recognised in chemistry and biology. Although the CH–π hydrogen bond and conventional hydrogen bonds share common features such as directionality, this weak interaction has played a secondary role in molecular recognition. In this study, we have devised a host–guest complex that is assembled solely by the CH–π hydrogen bonds. Multivalent interactions of a bowl-shaped hydrocarbon with its peripheral hydrogen atoms are made possible via CH–π hydrogen bonds by adopting a tubular hydrocarbon as a host for their enthalpy-driven complexation. Concyclic arrays of weak hydrogen bonds further allow dynamic rotational motions of the guest in the host. Solid-state analysis with crystallographic and spectroscopic methods reveal a single-axis rotation of the bowl in the tube.
Gender differences in individual variation in academic grades fail to fit expected patterns for STEM
Authors: O’Dea R. E. , Lagisz M. , Jennions M. D. , Nakagawa S.
Published: September 2018

Fewer women than men pursue careers in science, technology, engineering and mathematics (STEM), despite girls outperforming boys at school in the relevant subjects. According to the ‘variability hypothesis’, this over-representation of males is driven by gender differences in variance; greater male variability leads to greater numbers of men who exceed the performance threshold. Here, we use recent meta-analytic advances to compare gender differences in academic grades from over 1.6 million students. In line with previous studies we find strong evidence for lower variation among girls than boys, and of higher average grades for girls. However, the gender differences in both mean and variance of grades are smaller in STEM than non-STEM subjects, suggesting that greater variability is insufficient to explain male over-representation in STEM. Simulations of these differences suggest the top 10% of a class contains equal numbers of girls and boys in STEM, but more girls in non-STEM subjects.
Rehabilitative exercise and spatially patterned nanofibrillar scaffolds enhance vascularization and innervation following volumetric muscle loss
Authors: Nakayama Karina H. , Alcazar Cynthia , Yang Guang , Quarta Marco , Paine Patrick , Doan Linda , Davies Adam , Rando Thomas A. , Huang Ngan F.
Published: September 2018

Muscle regeneration can be permanently impaired by traumatic injuries, despite the high regenerative capacity of skeletal muscle. Implantation of engineered biomimetic scaffolds to the site of muscle ablation may serve as an attractive off-the-shelf therapeutic approach. The objective of the study was to histologically assess the therapeutic benefit of a three-dimensional spatially patterned collagen scaffold, in conjunction with rehabilitative exercise, for treatment of volumetric muscle loss. To mimic the physiologic organization of skeletal muscle, which is generally composed of myofibers aligned in parallel, three-dimensional parallel-aligned nanofibrillar collagen scaffolds were fabricated. When implanted into the ablated murine tibialis anterior muscle, the aligned nanofibrillar scaffolds, in conjunction with voluntary caged wheel exercise, significantly improved the density of perfused microvessels, in comparison to treatments of the randomly oriented nanofibrillar scaffold, decellularized scaffold, or in the untreated control group. The abundance of neuromuscular junctions was 19-fold higher when treated with aligned nanofibrillar scaffolds in conjunction with exercise, in comparison to treatment of aligned scaffold without exercise. Although, the density of de novo myofibers was not significantly improved by aligned scaffolds, regardless of exercise activity, the cross-sectional area of regenerating myofibers was increased by > 60% when treated with either aligned and randomly oriented scaffolds, in comparison to treatment of decellularized scaffold or untreated controls. These findings demonstrate that voluntary exercise improved the regenerative effect of aligned scaffolds by augmenting neurovascularization, and have important implications in the design of engineered biomimetic scaffolds for treatment of traumatic muscle injury.
Magnetic domain walls as broadband spin wave and elastic magnetisation wave emitters
Authors: Holländer Rasmus B. , Müller Cai , Schmalz Julius , Gerken Martina , McCord Jeffrey
Published: September 2018

We report on the direct observation of spin wave and elastic wave emission from magnetic domain walls in ferromagnetic thin films. Driven by alternating homogeneous magnetic fields the magnetic domain walls act as coherent magnetisation wave sources. Directional and low damped elastic waves below and above the ferromagnetic resonance are excited. The wave vector of the magnetoelastically induced acoustic waves is tuned by varying the excitation frequency. The occurrence of elastic wave emission is proved by a combination of micromagnetic and mechanical finite element simulations. Domain wall emitted magnetostatic surface spin waves occur at higher frequencies, which characteristics are confirmed by micromagnetic simulations. The distinct modes of magnetisation wave excitation from micromagnetic objects are a general physical phenomenon relevant for dynamic magnetisation processes in structured magnetic films. Magnetic domain walls can act as reconfigurable antennas for spin wave and elastic wave generation. The wave orientation can be controlled separately via the domain wall orientation for elastic waves and via magnetization orientation for magnetostatic surface spin waves.
Hotspots of soil organic carbon storage revealed by laboratory hyperspectral imaging
Authors: Hobley Eleanor , Steffens Markus , Bauke Sara L. , Kögel-Knabner Ingrid
Published: September 2018

Subsoil organic carbon (OC) is generally lower in content and more heterogeneous than topsoil OC, rendering it difficult to detect significant differences in subsoil OC storage. We tested the application of laboratory hyperspectral imaging with a variety of machine learning approaches to predict OC distribution in undisturbed soil cores. Using a bias-corrected random forest we were able to reproduce the OC distribution in the soil cores with very good to excellent model goodness-of-fit, enabling us to map the spatial distribution of OC in the soil cores at very high resolution (~53 × 53 µm). Despite a large increase in variance and reduction in OC content with increasing depth, the high resolution of the images enabled statistically powerful analysis in spatial distribution of OC in the soil cores. In contrast to the relatively homogeneous distribution of OC in the plough horizon, the subsoil was characterized by distinct regions of OC enrichment and depletion, including biopores which contained ~2–10 times higher SOC contents than the soil matrix in close proximity. Laboratory hyperspectral imaging enables powerful, fine-scale investigations of the vertical distribution of soil OC as well as hotspots of OC storage in undisturbed samples, overcoming limitations of traditional soil sampling campaigns.
Mesocosm experiments reveal the impact of mosquito control measures on malaria vector life history and population dynamics
Authors: Ng’habi Kija , Viana Mafalda , Matthiopoulos Jason , Lyimo Issa , Killeen Gerry , Ferguson Heather M.
Published: September 2018

The impact of control measures on mosquito vector fitness and demography is usually estimated from bioassays or indirect variables in the field. Whilst indicative, neither approach is sufficient to quantify the potentially complex response of mosquito populations to combined interventions. Here, large replicated mesocosms were used to measure the population-level response of the malaria vector Anopheles arabiensis to long-lasting insecticidal nets (LLINs) when used in isolation, or combined with insecticidal eave louvers (EL), or treatment of cattle with the endectocide Ivermectin (IM). State-space models (SSM) were fit to these experimental data, revealing that LLIN introduction reduced adult mosquito survival by 91% but allowed population persistence. ELs provided no additional benefit, but IM reduced mosquito fecundity by 59% and nearly eliminated all populations when combined with LLINs. This highlights the value of IM for integrated vector control, and mesocosm population experiments combined with SSM for identifying optimal combinations for vector population elimination.
Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney
Authors: Puranik Amrutesh S. , Leaf Irina A. , Jensen Mark A. , Hedayat Ahmad F. , Saad Ahmad , Kim Ki-Wook , Saadalla Abdulrahman M. , Woollard John R. , Kashyap Sonu , Textor Stephen C. , Grande Joseph P. , Lerman Amir , Simari Robert D. , Randolph Gwendalyn J. , Duffield Jeremy S. , Lerman Lilach O.
Published: September 2018

Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMϕ, CD11cloMϕ are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMϕ and CD11cloMϕ increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using liposomal clodronate and bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways.
Adolescent cannabinoid exposure induces irritability-like behavior and cocaine cross-sensitization without affecting the escalation of cocaine self-administration in adulthood
Authors: Kononoff Jenni , Melas Philippe A. , Kallupi Marsida , de Guglielmo Giordano , Kimbrough Adam , Scherma Maria , Fadda Paola , Kandel Denise B. , Kandel Eric R. , George Olivier
Published: September 2018

Cannabis use is typically initiated during adolescence and is a significant risk factor for the development of cocaine use in adulthood. However, no preclinical studies have examined the effects of adolescent cannabinoid exposure on cocaine dependence in adulthood using the escalation model of cocaine self-administration and the assessment of negative emotional states. In the present study, we found that exposure to the cannabinoid receptor agonist WIN55,212-2 (WIN) in adolescence produced irritability-like behavior and psychomotor cross-sensitization to cocaine in adolescence. In adulthood, rats were allowed to self-administer cocaine. The acquisition of cocaine self-administration was lower in rats with adolescent WIN exposure compared with controls. However, both WIN-exposed and control rats escalated their cocaine intake at the same rate, had similar responding under a progressive-ratio schedule of reinforcement, and had similar psychomotor responses to cocaine. Interestingly, the increase in irritability-like behavior that was previously observed in adolescence after WIN exposure persisted into adulthood. Whether the persisting increase in irritability-like behavior after WIN exposure has translational relevance remains to be studied. In summary, these results suggest that psychoactive cannabinoid exposure during adolescence is unlikely to have a major effect on the escalation of cocaine intake or the development of compulsive-like responding per se in adulthood in a rat model of cocaine self-administration. However, whether the persisting irritability-like behavior may predispose an individual to mood-related impairments in adulthood or predict such impairments warrants further investigation.
Highly tunable repetition-rate multiplication of mode-locked lasers using all-fibre harmonic injection locking
Authors: Jeon Chan-Gi , Zhang Shuangyou , Shin Junho , Kim Jungwon
Published: September 2018

Higher repetition-rate optical pulse trains have been desired for various applications such as high-bit-rate optical communication, photonic analogue-to-digital conversion, and multi-photon imaging. Generation of multi GHz and higher repetition-rate optical pulse trains directly from mode-locked oscillators is often challenging. As an alternative, harmonic injection locking can be applied for extra-cavity repetition-rate multiplication (RRM). Here we have investigated the operation conditions and achievable performances of all-fibre, highly tunable harmonic injection locking-based pulse RRM. We show that, with slight tuning of slave laser length, highly tunable RRM is possible from a multiplication factor of 2 to >100. The resulting maximum SMSR is 41 dB when multiplied by a factor of two. We further characterize the noise properties of the multiplied signal in terms of phase noise and relative intensity noise. The resulting absolute rms timing jitter of the multiplied signal is in the range of 20 fs to 60 fs (10 kHz–1MHz) for different multiplication factors. With its high tunability, simple and robust all-fibre implementation, and low excess noise, the demonstrated RRM system may find diverse applications in microwave photonics, optical communications, photonic analogue-to-digital conversion, and clock distribution networks.
Hierarchical Aerographite 3D flexible networks hybridized by InP micro/nanostructures for strain sensor applications
Authors: Plesco Irina , Strobel Julian , Schütt Fabian , Himcinschi Cameliu , Ben Sedrine Nabiha , Monteiro Teresa , Correia Maria Rosário , Gorceac Leonid , Cinic Boris , Ursaki Veaceslav , Marx Janik , Fiedler Bodo , Mishra Yogendra Kumar , Kienle Lorenz , Adelung Rainer , Tiginyanu Ion
Published: September 2018

In the present work, we report on development of three-dimensional flexible architectures consisting of an extremely porous three-dimensional Aerographite (AG) backbone decorated by InP micro/nanocrystallites grown by a single step hydride vapor phase epitaxy process. The systematic investigation of the hybrid materials by scanning electron microscopy demonstrates a rather uniform spatial distribution of InP crystallites without agglomeration on the surface of Aerographite microtubular structures. X-ray diffraction, transmission electron microscopy and Raman scattering analysis demonstrate that InP crystallites grown on bare Aerographite are of zincblende structure, while a preliminary functionalization of the Aerographite backbone with Au nanodots promotes the formation of crystalline In2O3 nanowires as well as gold-indium oxide core-shell nanostructures. The electromechanical properties of the hybrid AG-InP composite material are shown to be better than those of previously reported bare AG and AG-GaN networks. Robustness, elastic behavior and excellent translation of the mechanical deformation to variations in electrical conductivity highlight the prospects of AG-InP applications in tactile/strain sensors and other device structures related to flexible electronics.
Method for high frequency tracking and sub-nm sample stabilization in single molecule fluorescence microscopy
Authors: Schmidt Patrick D. , Reichert Benjamin H. , Lajoie John G. , Sivasankar Sanjeevi
Published: September 2018

While fluorescence microscopes and atomic force microscopes are widely used to visualize, track, and manipulate single biomolecules, the resolution of these methods is limited by sample drift. To minimize drift, active feedback methods have recently been used to stabilize single molecule microscopes on the sub-nanometer scale. However, these methods require high intensity lasers which limits their application in single molecule fluorescence measurements. Furthermore, these feedback methods do not track user-defined regions of the sample, but rather monitor the relative displacement of an unknown point on a fiducial marker, which limits their use in biological force measurements. To overcome these limitations, we have developed a novel method to image, track and stabilize a sample using low laser intensities. We demonstrate the capabilities of our approach by tracking a user-chosen point on a fiducial marker at 8.6 kHz and stabilizing it with sub-nanometer resolution. We further showcase the application of our method in single molecule fluorescence microscopy by imaging and stabilizing individual fluorescently-tagged streptavidin proteins under biologically relevant conditions. We anticipate that our method can be easily used to improve the resolution of a wide range of single molecule fluorescence microscopy and integrated force-fluorescence applications.
Assembly of Plasmonic and Magnetic Nanoparticles with Fluorescent Silica Shell Layer for Tri-functional SERS-Magnetic-Fluorescence Probes and Its Bioapplications
Authors: Kim Hyung-Mo , Kim Dong-Min , Jeong Cheolhwan , Park So Yeon , Cha Myeong Geun , Ha Yuna , Jang Dahye , Kyeong San , Pham Xuan-Hung , Hahm Eunil , Lee Sang Hun , Jeong Dae Hong , Lee Yoon-Sik , Kim Dong-Eun , Jun Bong-Hyun
Published: September 2018

In this study, we report on the fabrication of multilayered tri-functional magnetic-SERS-fluorescence nanoprobes (MF-SERS particles) containing clustered superparamagnetic Fe3O4 nanoparticles (NPs), silver NPs, and a fluorescent silica layer. The MF-SERS particles exhibited strong SERS signals from the silver NPs as well as both superparamagnetism and fluorescence. MF–SERS particles were uptaken by cells, allowing successful separation using an external magnetic field. SERS and fluorescence signals could be detected from the NP-containing cells, and CD44 antibody-conjugated MF-SERS particles selectively targeted MDA-MB-231 cells. Based on these properties, MF-SERS particles proved to be a useful nanoprobe for multiplex detection and separation of cancer cells.
sox9b is required in cardiomyocytes for cardiac morphogenesis and function
Authors: Gawdzik Joseph C. , Yue Monica S. , Martin Nathan R. , Elemans Loes M. H. , Lanham Kevin A. , Heideman Warren , Rezendes Ryan , Baker Tracie R. , Taylor Michael R. , Plavicki Jessica S.
Published: September 2018

The high mobility group transcription factor SOX9 is expressed in stem cells, progenitor cells, and differentiated cell-types in developing and mature organs. Exposure to a variety of toxicants including dioxin, di(2-ethylhexyl) phthalate, 6:2 chlorinated polyfluorinated ether sulfonate, and chlorpyrifos results in the downregulation of tetrapod Sox9 and/or zebrafish sox9b. Disruption of Sox9/sox9b function through environmental exposures or genetic mutations produce a wide range of phenotypes and adversely affect organ development and health. We generated a dominant-negative sox9b (dnsox9b) to inhibit sox9b target gene expression and used the Gal4/UAS system to drive dnsox9b specifically in cardiomyocytes. Cardiomyocyte-specific inhibition of sox9b function resulted in a decrease in ventricular cardiomyocytes, an increase in atrial cardiomyocytes, hypoplastic endothelial cushions, and impaired epicardial development, ultimately culminating in heart failure. Cardiomyocyte-specific dnsox9b expression significantly reduced end diastolic volume, which corresponded with a decrease in stroke volume, ejection fraction, and cardiac output. Further analysis of isolated cardiac tissue by RT-qPCR revealed cardiomyocyte-specific inhibition of sox9b function significantly decreased the expression of the critical cardiac development genes nkx2.5, nkx2.7, and myl7, as well as c-fos, an immediate early gene necessary for cardiomyocyte progenitor differentiation. Together our studies indicate sox9b transcriptional regulation is necessary for cardiomyocyte development and function.