bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass and Fine‐Scale Morphological Changes Induced by Changing Seawater pH in the Coccolith Gephyrocapsa oceanica
Authors: Hermoso Michaël , Minoletti Fabrice 
Published: August 2018

AbstractCoccolithophores have been extensively studied to understand the environmental control on calcification in a key biological group influencing the alkalinity of seawater. Previous studies have established that bulk calcification scales with cell division rates under a wide range of pH conditions. Yet the fine‐scale ultrastructural changes of the coccoliths and therefore the pH‐sensitive underlying mechanisms altering biomineralization of the coccoliths remain largely underconstrained. Using circularly polarized light and high‐resolution microscopy, we have generated mass estimates of cultured Gephyrocapsa oceanica coccoliths grown in media with pH values ranging from 7.4 to 9.0. These mass estimates representing a bulk calcification response were related to the morphological changes within the coccoliths. From optimal (pH 8.6) down to pH 7.4 conditions, we have observed that impaired cell growth and lower calcite quota are accompanied by a 35% decrease in mean coccolith mass. The data further show that seawater acidification does not homogenously affect calcification of the coccoliths, as a clear decrease of the breadth of the tube (a structure surrounding the central area of the coccoliths) was detected, whereas all other ultrastructural components were far less impacted. We discuss this specific sensitivity to acidification as the possible consequence of the altered interaction of the acidic polysaccharides used for biomineralization and ambient concentration of protons released by calcification that substantially modify the growth patterns, the morphology, and ultimately the mass of the coccoliths.
Metamorphic Zonation by Out‐of‐Sequence Thrusting at Back‐Stepping Subduction Zones: Sequential Accretion of the Caledonian Internides, Central Sweden
Authors: Bender H. , Ring U. , Almqvist B. S. G. , Grasemann B. , Stephens M. B. 
Published: August 2018

AbstractExhumation of the high‐grade metamorphic Seve Nappe Complex and its emplacement between lower‐grade nappes has been related to wedge extrusion in the central Scandinavian Caledonides. To test this hypothesis, the kinematic evolution of the Caledonian nappe pile is studied by systematic structural mapping in central and northern Jämtland, Sweden. Structural data, combined with petrological and quartz microstructure observations, document pervasive top‐to‐the‐ESE, foreland‐directed shearing under progressively decreasing metamorphic grade across the entire nappe pile. Mylonitic foliation, foliation‐parallel boudinage, and abundant top‐to‐the‐ESE and rare, scattered top‐to‐the‐WNW shear‐sense indicators imply foreland‐directed general shear. This deformation regime caused exhumation by concurrent thrusting and vertical ductile thinning. We propose a specific succession of in‐ and out‐of‐sequence thrusts that generated the metamorphic zonation. Our model envisions in‐sequence propagation of thrusts during exhumation of the Seve Nappe Complex, related to subduction of Baltica beneath a volcanic arc within Iapetus. Concurrently, Iapetus subducted beneath Laurentia farther to the west. When Iapetus was closed, Baltica subduction stepped westward and continued beneath Laurentia. The back stepping of subduction at the onset of continental collision caused out‐of‐sequence propagation of the orogenic wedge. Thrusting cut downsection across the existing tectonostratigraphy, emplacing units of lower metamorphic grade above the high‐grade Seve Nappe Complex. This imbrication generated the present metamorphic zonation of the Caledonian nappe pile during sustained convergence between Laurentia and Baltica.
Design rules for a tunable merged-tip microneedle
Authors: Lim Jungeun , Tahk Dongha , Yu James , Min Dal-Hee , Jeon Noo Li 
Published: August 2018

AbstractThis publication proposes the use of an elasto-capillarity-driven self-assembly for fabricating a microscale merged-tip structure out of a variety of biocompatible UV-curable polymers for use as a microneedle platform. In addition, the novel merged-tip microstructure constitutes a new class of microneedles, which incorporates the convergence of biocompatible polymer micropillars, leading to the formation of a sharp tip and an open cavity capable of both liquid trapping and volume control. When combined with biocompatible photopolymer micropillar arrays fabricated with photolithography, elasto-capillarity-driven self-assembly provides a means for producing a complex microneedle-like structure without the use of micromolding or micromachining. This publication also explores and defines the design rules by which several fabrication aspects, such as micropillar dimensions, shapes, pattern array configurations, and materials, can be manipulated to produce a customizable microneedle array with controllable cavity volumes, fracture points, and merge profiles. In addition, the incorporation of a modular through-hole micropore membrane base was also investigated as a method for constitutive payload delivery and fluid-sampling functionalities. The flexibility and fabrication simplicity of the merged-tip microneedle platform holds promise in transdermal drug delivery applications.
MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability
Authors: Dingar Dharmendra , Tu William B. , Resetca Diana , Lourenco Corey , Tamachi Aaliya , De Melo Jason , Houlahan Kathleen E. , Kalkat Manpreet , Chan Pak-Kei , Boutros Paul C. , Raught Brian , Penn Linda Z. 
Published: August 2018

AbstractThe c-MYC (MYC) oncoprotein is deregulated in over 50% of cancers, yet regulatory mechanisms controlling MYC remain unclear. To this end, we interrogated the MYC interactome using BioID mass spectrometry (MS) and identified PP1 (protein phosphatase 1) and its regulatory subunit PNUTS (protein phosphatase-1 nuclear-targeting subunit) as MYC interactors. We demonstrate that endogenous MYC and PNUTS interact across multiple cell types and that they co-occupy MYC target gene promoters. Inhibiting PP1 by RNAi or pharmacological inhibition results in MYC hyperphosphorylation at multiple serine and threonine residues, leading to a decrease in MYC protein levels due to proteasomal degradation through the canonical SCFFBXW7 pathway. MYC hyperphosphorylation can be rescued specifically with exogenous PP1, but not other phosphatases. Hyperphosphorylated MYC retained interaction with its transcriptional partner MAX, but binding to chromatin is significantly compromised. Our work demonstrates that PP1/PNUTS stabilizes chromatin-bound MYC in proliferating cells.
Oxidising agents in sub-arc mantle melts link slab devolatilisation and arc magmas
Authors: Bénard Antoine , Klimm Kevin , Woodland Alan B. , Arculus Richard J. , Wilke Max , Botcharnikov Roman E. , Shimizu Nobumichi , Nebel Oliver , Rivard Camille , Ionov Dmitri A. 
Published: August 2018

AbstractSubduction zone magmas are more oxidised on eruption than those at mid-ocean ridges. This is attributed either to oxidising components, derived from subducted lithosphere (slab) and added to the mantle wedge, or to oxidation processes occurring during magma ascent via differentiation. Here we provide direct evidence for contributions of oxidising slab agents to melts trapped in the sub-arc mantle. Measurements of sulfur (S) valence state in sub-arc mantle peridotites identify sulfate, both as crystalline anhydrite (CaSO4) and dissolved SO42− in spinel-hosted glass (formerly melt) inclusions. Copper-rich sulfide precipitates in the inclusions and increased Fe3+/∑Fe in spinel record a S6+–Fe2+ redox coupling during melt percolation through the sub-arc mantle. Sulfate-rich glass inclusions exhibit high U/Th, Pb/Ce, Sr/Nd and δ34S (+ 7 to + 11‰), indicating the involvement of dehydration products of serpentinised slab rocks in their parental melt sources. These observations provide a link between liberated slab components and oxidised arc magmas.
Intrinsic neuronal dynamics predict distinct functional roles during working memory
Authors: Wasmuht D. F. , Spaak E. , Buschman T. J. , Miller E. K. , Stokes M. G. 
Published: August 2018

AbstractWorking memory (WM) is characterized by the ability to maintain stable representations over time; however, neural activity associated with WM maintenance can be highly dynamic. We explore whether complex population coding dynamics during WM relate to the intrinsic temporal properties of single neurons in lateral prefrontal cortex (lPFC), the frontal eye fields (FEF), and lateral intraparietal cortex (LIP) of two monkeys (Macaca mulatta). We find that cells with short timescales carry memory information relatively early during memory encoding in lPFC; whereas long-timescale cells play a greater role later during processing, dominating coding in the delay period. We also observe a link between functional connectivity at rest and the intrinsic timescale in FEF and LIP. Our results indicate that individual differences in the temporal processing capacity predict complex neuronal dynamics during WM, ranging from rapid dynamic encoding of stimuli to slower, but stable, maintenance of mnemonic information.
Argininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer
Authors: Baruteau Julien , Perocheau Dany P. , Hanley Joanna , Lorvellec Maëlle , Rocha-Ferreira Eridan , Karda Rajvinder , Ng Joanne , Suff Natalie , Diaz Juan Antinao , Rahim Ahad A. , Hughes Michael P. , Banushi Blerida , Prunty Helen , Hristova Mariya , Ridout Deborah A. , Virasami Alex , Heales Simon , Howe Stewen J. , Buckley Suzanne M. K. , Mills Philippa B. , Gissen Paul , Waddington Simon N. 
Published: August 2018

AbstractArgininosuccinate lyase (ASL) belongs to the hepatic urea cycle detoxifying ammonia, and the citrulline-nitric oxide (NO) cycle producing NO. ASL-deficient patients present argininosuccinic aciduria characterised by hyperammonaemia, multiorgan disease and neurocognitive impairment despite treatment aiming to normalise ammonaemia without considering NO imbalance. Here we show that cerebral disease in argininosuccinic aciduria involves neuronal oxidative/nitrosative stress independent of hyperammonaemia. Intravenous injection of AAV8 vector into adult or neonatal ASL-deficient mice demonstrates long-term correction of the hepatic urea cycle and the cerebral citrulline-NO cycle, respectively. Cerebral disease persists if ammonaemia only is normalised but is dramatically reduced after correction of both ammonaemia and neuronal ASL activity. This correlates with behavioural improvement and reduced cortical cell death. Thus, neuronal oxidative/nitrosative stress is a distinct pathophysiological mechanism from hyperammonaemia. Disease amelioration by simultaneous brain and liver gene transfer with one vector, to treat both metabolic pathways, provides new hope for hepatocerebral metabolic diseases.
A general deoxygenation approach for synthesis of ketones from aromatic carboxylic acids and alkenes
Authors: Zhang Muliang , Xie Jin , Zhu Chengjian 
Published: August 2018

AbstractThe construction of an aryl ketone structural unit by means of catalytic carbon–carbon coupling reactions represents the state-of-the-art in organic chemistry. Herein we achieved the direct deoxygenative ketone synthesis in aqueous solution from readily available aromatic carboxylic acids and alkenes, affording structurally diverse ketones in moderate to good yields. Visible-light photoredox catalysis enables the direct deoxygenation of acids as acyl sources with triphenylphosphine and represents a distinct perspective on activation. The synthetic robustness is supported by the late-stage modification of several pharmaceutical compounds and complex molecules. This ketone synthetic strategy is further applied to the synthesis of the drug zolpidem in three steps with 50% total yield and a concise construction of cyclophane-braced 18–20 membered macrocycloketones. It represents not only the advancement for the streamlined synthesis of aromatic ketones from feedstock chemicals, but also a photoredox radical activation mode beyond the redox potential of carboxylic acids.
System immunology-based identification of blood transcriptional modules correlating to antibody responses in sheep
Authors: Braun Roman Othmar , Brunner Livia , Wyler Kurt , Auray Gaël , García-Nicolás Obdulio , Python Sylvie , Zumkehr Beatrice , Gaschen Véronique , Stoffel Michael Hubert , Collin Nicolas , Barnier-Quer Christophe , Bruggmann Rémy , Summerfield Artur 
Published: August 2018

AbstractLacking immunogenicity, inactivated vaccines require potent adjuvants. To understand their effects, we used a system immunology-based analysis of ovine blood transcriptional modules (BTMs) to dissect innate immune responses relating to either antibody or haptoglobin levels. Using inactivated foot-and-mouth disease virus as an antigen, we compared non-adjuvanted to liposomal-formulated vaccines complemented or not with TLR4 and TLR7 ligands. Early after vaccination, BTM relating to myeloid cells, innate immune responses, dendritic cells, and antigen presentation correlated positively, whereas BTM relating to T and natural killer cells, as well as cell cycle correlated negatively with antibody responses. Interestingly, BTM relating to myeloid cells, inflammation and antigen presentation also correlated with haptoglobin, but in a reversed manner, indicating that acute systemic inflammation is not beneficial for early antibody responses. Analysis of vaccine-dependent BTM modulation showed that liposomal formulations induced similar responses to those correlating to antibody levels, while addition of TLR ligands reduced myeloid cells, inflammation and antigen presentation BTM expression despite promoting antibody responses. Furthermore, this vaccine was more potent at downregulating T and natural killer cell BTM. When pre-vaccination BTM were analyzed, we found that high vaccine responders expressed higher levels of cell cycle and myeloid cell BTMs as compared with low responders. In conclusion, we have transferred human BTM to sheep and identified early vaccine-induced responses associated with antibody levels or unwanted inflammation. Such readouts are applicable to other veterinary species and very useful to identify efficient vaccine adjuvants, their mechanism of action, and factors related to low responders.
OsPIN1b is Involved in Rice Seminal Root Elongation by Regulating Root Apical Meristem Activity in Response to Low Nitrogen and Phosphate
Authors: Sun Huwei , Tao Jinyuan , Bi Yang , Hou Mengmeng , Lou Jiajing , Chen Xinni , Zhang Xuhong , Luo Le , Xie Xiaonan , Yoneyama Koichi , Zhao Quanzhi , Xu Guohua , Zhang Yali 
Published: August 2018

AbstractThe response of plant root development to nutrient deficiencies is critical for crop production. Auxin, nitric oxide (NO), and strigolactones (SLs) are important regulators of root growth under low-nitrogen and -phosphate (LN and LP) conditions. Polar auxin transport in plants, which is mainly dependent on auxin efflux protein PINs, creates local auxin maxima to form the basis for root initiation and elongation; however, the PIN genes that play an important role in LN- and LP-modulated root growth remain unclear. qRT-PCR analysis of OsPIN family genes showed that the expression of OsPIN1b is most abundant in root tip and is significantly downregulated by LN, LP, sodium nitroprusside (SNP, NO donor), and GR24 (analogue of SLs) treatments. Seminal roots in ospin1b mutants were shorter than those of the wild type; and the seminal root, [3H]IAA transport, and IAA concentration responses to LN, LP, SNP, and GR24 application were attenuated in ospin1b-1 mutants. pCYCB1;1::GUS expression was upregulated by LN, LP, SNP, and GR24 treatments in wild type, but not in the ospin1b-1 mutant, suggesting that OsPIN1b is involved in auxin transport and acts as a downstream mediator of NO and SLs to induce meristem activity in root tip in rice under LN and LP.
Domestic horses (Equus caballus) discriminate between negative and positive human nonverbal vocalisations
Authors: Smith Amy Victoria , Proops Leanne , Grounds Kate , Wathan Jennifer , Scott Sophie K , McComb Karen 
Published: August 2018

AbstractThe ability to discriminate between emotion in vocal signals is highly adaptive in social species. It may also be adaptive for domestic species to distinguish such signals in humans. Here we present a playback study investigating whether horses spontaneously respond in a functionally relevant way towards positive and negative emotion in human nonverbal vocalisations. We presented horses with positively- and negatively-valenced human vocalisations (laughter and growling, respectively) in the absence of all other emotional cues. Horses were found to adopt a freeze posture for significantly longer immediately after hearing negative versus positive human vocalisations, suggesting that negative voices promote vigilance behaviours and may therefore be perceived as more threatening. In support of this interpretation, horses held their ears forwards for longer and performed fewer ear movements in response to negative voices, which further suggest increased vigilance. In addition, horses showed a right-ear/left-hemisphere bias when attending to positive compared with negative voices, suggesting that horses perceive laughter as more positive than growling. These findings raise interesting questions about the potential for universal discrimination of vocal affect and the role of lifetime learning versus other factors in interspecific communication.
Ras-dva small GTPases lost during evolution of amniotes regulate regeneration in anamniotes
Authors: Ivanova Anastasiya S. , Korotkova Daria D. , Ermakova Galina V. , Martynova Natalia Yu. , Zaraisky Andrey G. , Tereshina Maria B. 
Published: August 2018

AbstractIn contrast to amniotes (reptiles, birds and mammals), anamniotes (fishes and amphibians) can effectively regenerate body appendages such as fins, limbs and tails. Why such a useful capability was progressively lost in amniotes remains unknown. As we have hypothesized recently, one of the reasons for this could be loss of some genes regulating the regeneration in evolution of amniotes. Here, we demonstrate the validity of this hypothesis by showing that genes of small GTPases Ras-dva1 and Ras-dva2, that had been lost in a stepwise manner during evolution of amniotes and disappeared completely in placental mammals, are important for regeneration in anamniotes. Both Ras-dva genes are quickly activated in regenerative wound epithelium and blastema forming in the amputated adult Danio rerio fins and Xenopus laevis tadpoles’ tails and hindlimb buds. Down-regulation of any of two Ras-dva genes in fish and frog resulted in a retardation of regeneration accompanied by down-regulation of the regeneration marker genes. On the other hand, Ras-dva over-expression in tadpoles’ tails restores regeneration capacity during the refractory period when regeneration is blocked due to natural reasons. Thus our data on Ras-dva genes, which were eliminated in amniotes but play role in anamniotes regeneration regulation, satisfy our hypothesis.
Reconciling material cultures in archaeology with genetic data: The nomenclature of clusters emerging from archaeogenomic analysis
Authors: Eisenmann Stefanie , Bánffy Eszter , van Dommelen Peter , Hofmann Kerstin P. , Maran Joseph , Lazaridis Iosif , Mittnik Alissa , McCormick Michael , Krause Johannes , Reich David , Stockhammer Philipp W. 
Published: August 2018

AbstractGenome-wide ancient DNA analysis of skeletons retrieved from archaeological excavations has provided a powerful new tool for the investigation of past populations and migrations. An important objective for the coming years is to properly integrate ancient genomics into archaeological research. This article aims to contribute to developing a better understanding and cooperation between the two disciplines and beyond. It focuses on the question of how best to name clusters encountered when analysing the genetic makeup of past human populations. Recent studies have frequently borrowed archaeological cultural designations to name these genetic groups, while neglecting the historically problematic nature of the concept of cultures in archaeology. After reviewing current practices in naming genetic clusters, we introduce three possible nomenclature systems (‘numeric system’, ‘mixed system (a)’, ‘geographic-temporal system’) along with their advantages and challenges.
Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening
Authors: Puls T. J. , Tan Xiaohong , Husain Mahera , Whittington Catherine F. , Fishel Melissa L. , Voytik-Harbin Sherry L. 
Published: August 2018

AbstractWhile much progress has been made in the war on cancer, highly invasive cancers such as pancreatic cancer remain difficult to treat and anti-cancer clinical trial success rates remain low. One shortcoming of the drug development process that underlies these problems is the lack of predictive, pathophysiologically relevant preclinical models of invasive tumor phenotypes. While present-day 3D spheroid invasion models more accurately recreate tumor invasion than traditional 2D models, their shortcomings include poor reproducibility and inability to interface with automated, high-throughput systems. To address this gap, a novel 3D tumor-tissue invasion model which supports rapid, reproducible setup and user-definition of tumor and surrounding tissue compartments was developed. High-cell density tumor compartments were created using a custom-designed fabrication system and standardized oligomeric type I collagen to define and modulate ECM physical properties. Pancreatic cancer cell lines used within this model showed expected differential invasive phenotypes. Low-passage, patient-derived pancreatic cancer cells and cancer-associated fibroblasts were used to increase model pathophysiologic relevance, yielding fibroblast-mediated tumor invasion and matrix alignment. Additionally, a proof-of-concept multiplex drug screening assay was applied to highlight this model’s ability to interface with automated imaging systems and showcase its potential as a predictive tool for high-throughput, high-content drug screening.
Septins are critical regulators of osteoclastic bone resorption
Authors: Møller Anaïs M. J. , Füchtbauer Ernst-Martin , Brüel Annemarie , Andersen Thomas L. , Borggaard Xenia G. , Pavlos Nathan J. , Thomsen Jesper S. , Pedersen Finn S. , Delaisse Jean-Marie , Søe Kent 
Published: August 2018

AbstractSeptins are known to play key roles in supporting cytoskeletal stability, vesicular transport, endo-/exocytosis, stabilizing cellular membranes and forming diffusion barriers. Their function in mammalian cells is poorly investigated. The osteoclast offers an interesting tool to investigate septins because all cellular activities septins were reported to be involved in are critical for osteoclasts. However, the existence of septins in osteoclasts has not even been reported. Here we show that theSEPT9gene and Septin 9 (SEPT9) protein are expressed and synthesized during differentiation of human osteoclasts. Pharmacological stabilization of septin filaments dose dependently inhibits bone resorption of human osteoclastsin vitrosuggesting a role for septins in bone resorption. Attesting to this, conditional deletion ofSept9in mice leads to elevated levels of trabecular bone and diminished femoral growthin vivo. Finally, systematic interrogation of the spatial organization of SEPT9 by confocal microscopy reveals that SEPT9 is closely associated to the structures known to be critical for osteoclast activity. We propose that septins in general and SEPT9 in particular play a previously unappreciated role in osteoclastic bone resorption.