bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uplift of the central transantarctic mountains
Authors: Wannamaker Phil , Hill Graham , Stodt John , Maris Virginie , Ogawa Yasuo , Selway Kate , Boren Goran , Bertrand Edward , Uhlmann Daniel , Ayling Bridget , Green A. Marie , Feucht Daniel 
Published: November 2017

AbstractThe Transantarctic Mountains (TAM) are the world’s longest rift shoulder but the source of their high elevation is enigmatic. To discriminate the importance of mechanical vs. thermal sources of support, a 550 km-long transect of magnetotelluric geophysical soundings spanning the central TAM was acquired. These data reveal a lithosphere of high electrical resistivity to at least 150 km depth, implying a cold stable state well into the upper mantle. Here we find that the central TAM most likely are elevated by a non-thermal, flexural cantilever mechanism which is perhaps the most clearly expressed example anywhere. West Antarctica in this region exhibits a low resistivity, moderately hydrated asthenosphere, and concentrated extension (rift necking) near the central TAM range front but with negligible thermal encroachment into the TAM. Broader scale heat flow of east-central West Antarctica appears moderate, on the order of 60–70 mW m−2, lower than that of the U.S. Great Basin.
Deterministic and robust room-temperature exchange coupling in monodomain multiferroic BiFeO3 heterostructures
Authors: Saenrang W. , Davidson B. A. , Maccherozzi F. , Podkaminer J. P. , Irwin J. , Johnson R. D. , Freeland J. W. , Íñiguez J. , Schad J. L. , Reierson K. , Frederick J. C. , Vaz C. A. F. , Howald L. , Kim T. H. , Ryu S. , Veenendaal M. v. , Radaelli P. G. , Dhesi S. S. , Rzchowski M. S. , Eom C. B. 
Published: November 2017

AbstractExploiting multiferroic BiFeO3 thin films in spintronic devices requires deterministic and robust control of both internal magnetoelectric coupling in BiFeO3, as well as exchange coupling of its antiferromagnetic order to a ferromagnetic overlayer. Previous reports utilized approaches based on multi-step ferroelectric switching with multiple ferroelectric domains. Because domain walls can be responsible for fatigue, contain localized charges intrinsically or via defects, and present problems for device reproducibility and scaling, an alternative approach using a monodomain magnetoelectric state with single-step switching is desirable. Here we demonstrate room temperature, deterministic and robust, exchange coupling between monodomain BiFeO3 films and Co overlayer that is intrinsic (i.e., not dependent on domain walls). Direct coupling between BiFeO3 antiferromagnetic order and Co magnetization is observed, with ~ 90° in-plane Co moment rotation upon single-step switching that is reproducible for hundreds of cycles. This has important consequences for practical, low power non-volatile magnetoelectric devices utilizing BiFeO3.
Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity
Authors: Pantophlet Ralph , Trattnig Nino , Murrell Sasha , Lu Naiomi , Chau Dennis , Rempel Caitlin , Wilson Ian A. , Kosma Paul 
Published: November 2017

AbstractOligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system. One of these mimetics is bound avidly by members of a family of oligomannose-specific bnAbs and their putative common germline precursor when presented as a glycoconjugate. The crystal structure of one of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance. Lastly, immunization of human-antibody transgenic animals with a lead mimetic evokes nAbs with specificities approaching those of existing bnAbs. These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1.
Regulation of gene expression and RNA editing in Drosophila adapting to divergent microclimates
Authors: Yablonovitch Arielle L. , Fu Jeremy , Li Kexin , Mahato Simpla , Kang Lin , Rashkovetsky Eugenia , Korol Abraham B. , Tang Hua , Michalak Pawel , Zelhof Andrew C. , Nevo Eviatar , Li Jin Billy 
Published: November 2017

AbstractDetermining the mechanisms by which a species adapts to its environment is a key endeavor in the study of evolution. In particular, relatively little is known about how transcriptional processes are fine-tuned to adjust to different environmental conditions. Here we studyDrosophila melanogasterfrom ‘Evolution Canyon’ in Israel, which consists of two opposing slopes with divergent microclimates. We identify several hundred differentially expressed genes and dozens of differentially edited sites between flies from each slope, correlate these changes with genetic differences, and use CRISPR mutagenesis to validate that an intronic SNP inpromininregulates its editing levels. We also demonstrate that while temperature affects editing levels at more sites than genetic differences, genetically regulated sites tend to be less affected by temperature. This work shows the extent to which gene expression and RNA editing differ between flies from different microclimates, and provides insights into the regulation responsible for these differences.
Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses
Authors: Cruz-Adalia Aránzazu , Ramirez-Santiago Guillermo , Osuna-Pérez Jesús , Torres-Torresano Mónica , Zorita Virgina , Martínez-Riaño Ana , Boccasavia Viola , Borroto Aldo , Martínez del Hoyo Gloria , González-Granado José María , Alarcón Balbino , Sánchez-Madrid Francisco , Veiga Esteban 
Published: November 2017

AbstractBacterial phagocytosis and antigen cross-presentation to activate CD8+ T cells are principal functions of professional antigen presenting cells. However, conventional CD4+ T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8+ T cells, which proliferate and become cytotoxic in response. CD4+ T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8+ T cells with low PD-1 expression. Moreover, transphagocytic CD4+ T cells induce protective anti-tumour immune responses by priming CD8+ T cells, highlighting the potential of CD4+ T cells as a tool for cancer immunotherapy.
The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors
Authors: Boyé Kevin , Pujol Nadège , D Alves Isabel , Chen Ya-Ping , Daubon Thomas , Lee Yi-Zong , Dedieu Stephane , Constantin Marion , Bello Lorenzo , Rossi Marco , Bjerkvig Rolf , Sue Shih-Che , Bikfalvi Andreas , Billottet Clotilde 
Published: November 2017

AbstractCXCR3 plays important roles in angiogenesis, inflammation, and cancer. However, the precise mechanism of regulation and activity in tumors is not well known. We focused on CXCR3-A conformation and on the mechanisms controlling its activity and trafficking and investigated the role of CXCR3/LRP1 cross talk in tumor cell invasion. Here we report that agonist stimulation induces an anisotropic response with conformational changes of CXCR3-A along its longitudinal axis. CXCR3-A is internalized via clathrin-coated vesicles and recycled by retrograde trafficking. We demonstrate that CXCR3-A interacts with LRP1. Silencing of LRP1 leads to an increase in the magnitude of ligand-induced conformational change with CXCR3-A focalized at the cell membrane, leading to a sustained receptor activity and an increase in tumor cell migration. This was validated in patient-derived glioma cells and patient samples. Our study defines LRP1 as a regulator of CXCR3, which may have important consequences for tumor biology.
The energy cost of polypeptide knot formation and its folding consequences
Authors: Bustamante Andrés , Sotelo-Campos Juan , Guerra Daniel G. , Floor Martin , Wilson Christian A. M. , Bustamante Carlos , Báez Mauricio 
Published: November 2017

AbstractKnots are natural topologies of chains. Yet, little is known about spontaneous knot formation in a polypeptide chain—an event that can potentially impair its folding—and about the effect of a knot on the stability and folding kinetics of a protein. Here we used optical tweezers to show that the free energy cost to form a trefoil knot in the denatured state of a polypeptide chain of 120 residues is 5.8 ± 1 kcal mol−1. Monte Carlo dynamics of random chains predict this value, indicating that the free energy cost of knot formation is of entropic origin. This cost is predicted to remain above 3 kcal mol−1 for denatured proteins as large as 900 residues. Therefore, we conclude that naturally knotted proteins cannot attain their knot randomly in the unfolded state but must pay the cost of knotting through contacts along their folding landscape.
Redox-independent chromium isotope fractionation induced by ligand-promoted dissolution
Authors: Saad Emily M. , Wang Xiangli , Planavsky Noah J. , Reinhard Christopher T. , Tang Yuanzhi 
Published: November 2017

AbstractThe chromium (Cr) isotope system has emerged as a potential proxy for tracing the Earth’s atmospheric evolution based on a redox-dependent framework for Cr mobilization and isotope fractionation. Although studies have demonstrated that redox-independent pathways can also mobilize Cr, no quantitative constraints exist on the associated isotope fractionations. Here we survey the effects of common environmental ligands on the dissolution of Cr(III)-(oxy)hydroxide solids and associated Cr isotope fractionation. For a variety of organic acids and siderophores, δ53Cr values of dissolved Cr(III) are −0.27 to 1.23‰, within the range of previously observed Cr isotope signatures in rock records linked to Cr redox cycling. Thus, ligand-promoted dissolution of Cr-containing solids, a redox-independent process, must be taken into account when using sedimentary Cr isotope signatures to diagnose atmospheric oxygen levels. This work provides a step towards establishing a more robust framework for using Cr isotopes to track the evolution of the Earth’s atmosphere.
Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers
Authors: Zuliani-Alvarez Lorena , Marzeda Anna M. , Deligne Claire , Schwenzer Anja , McCann Fiona E. , Marsden Brian D. , Piccinini Anna M. , Midwood Kim S. 
Published: November 2017

AbstractPattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury, or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4)-mediated sterile inflammation. Here we map three sites within tenascin-C that directly and cooperatively interact with TLR4. We also identify a conserved inflammatory epitope in related proteins from diverse families, and demonstrate that its presence targets molecules for TLR detection, while its absence enables escape of innate immune surveillance. These data reveal a unique molecular code that defines endogenous proteins as inflammatory stimuli by marking them for recognition by TLRs.
Rapid neo-sex chromosome evolution and incipient speciation in a major forest pest
Authors: Bracewell Ryan R. , Bentz Barbara J. , Sullivan Brian T. , Good Jeffrey M. 
Published: November 2017

AbstractGenome evolution is predicted to be rapid following the establishment of new (neo) sex chromosomes, but it is not known if neo-sex chromosome evolution plays an important role in speciation. Here we combine extensive crossing experiments with population and functional genomic data to examine neo-XY chromosome evolution and incipient speciation in the mountain pine beetle. We find a broad continuum of intrinsic incompatibilities in hybrid males that increase in strength with geographic distance between reproductively isolated populations. This striking progression of reproductive isolation is coupled with extensive gene specialization, natural selection, and elevated genetic differentiation on both sex chromosomes. Closely related populations isolated by hybrid male sterility also show fixation of alternative neo-Y haplotypes that differ in structure and male-specific gene content. Our results suggest that neo-sex chromosome evolution can drive rapid functional divergence between closely related populations irrespective of ecological drivers of divergence.
Decoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition
Authors: Mitra Ramkrishna , Chen Xi , Greenawalt Evan J. , Maulik Ujjwal , Jiang Wei , Zhao Zhongming , Eischen Christine M. 
Published: November 2017

AbstractLong non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNADNM3OS,MEG3, andMIAToverexpression and their reproducible gene regulation in ovarian cancer EMT. Genome-wide mapping shows 73% ofMEG3-regulated EMT-linked pathway genes containMEG3binding sites.DNM3OSoverexpression, but notMEG3orMIAT, significantly correlates to worse overall patient survival.DNM3OSknockdown results in altered EMT-linked genes/pathways, mesenchymal-to-epithelial transition, and reduced cell migration and invasion. Proteotranscriptomic characterization further supports theDNM3OSand ovarian cancer EMT connection. TWIST1 overexpression andDNM3OSamplification provides an explanation for increasedDNM3OSlevels. Therefore, our results elucidate lncRNA that regulate EMT and demonstrateDNM3OSspecifically contributes to EMT in ovarian cancer.
The formation and evolution of Titan’s winter polar vortex
Authors: Teanby Nicholas A. , Bézard Bruno , Vinatier Sandrine , Sylvestre Melody , Nixon Conor A. , Irwin Patrick G. J. , de Kok Remco J. , Calcutt Simon B. , Flasar F. Michael 
Published: November 2017

AbstractSaturn’s largest moon Titan has a substantial nitrogen-methane atmosphere, with strong seasonal effects, including formation of winter polar vortices. Following Titan’s 2009 northern spring equinox, peak solar heating moved to the northern hemisphere, initiating south-polar subsidence and winter polar vortex formation. Throughout 2010–2011, strengthening subsidence produced a mesospheric hot-spot and caused extreme enrichment of photochemically produced trace gases. However, in 2012 unexpected and rapid mesospheric cooling was observed. Here we show extreme trace gas enrichment within the polar vortex dramatically increases mesospheric long-wave radiative cooling efficiency, causing unusually cold temperatures 2–6 years post-equinox. The long time-frame to reach a stable vortex configuration results from the high infrared opacity of Titan’s trace gases and the relatively long atmospheric radiative time constant. Winter polar hot-spots have been observed on other planets, but detection of post-equinox cooling is so far unique to Titan.
Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25
Authors: Scally Stephen W. , McLeod Brandon , Bosch Alexandre , Miura Kazutoyo , Liang Qi , Carroll Sean , Reponen Sini , Nguyen Ngan , Giladi Eldar , Rämisch Sebastian , Yusibov Vidadi , Bradley Allan , Lemiale Franck , Schief William R. , Emerling Daniel , Kellam Paul , King C. Richter , Julien Jean-Philippe 
Published: November 2017

AbstractThe Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.
Potential landscape of high dimensional nonlinear stochastic dynamics with large noise
Authors: Tang Ying , Yuan Ruoshi , Wang Gaowei , Zhu Xiaomei , Ao Ping 
Published: November 2017

AbstractQuantifying stochastic processes is essential to understand many natural phenomena, particularly in biology, including the cell-fate decision in developmental processes as well as the genesis and progression of cancers. While various attempts have been made to construct potential landscape in high dimensional systems and to estimate transition rates, they are practically limited to the cases where either noise is small or detailed balance condition holds. A general and practical approach to investigate real-world nonequilibrium systems, which are typically high-dimensional and subject to large multiplicative noise and the breakdown of detailed balance, remains elusive. Here, we formulate a computational framework that can directly compute the relative probabilities between locally stable states of such systems based on a least action method, without the necessity of simulating the steady-state distribution. The method can be applied to systems with arbitrary noise intensities through A-type stochastic integration, which preserves the dynamical structure of the deterministic counterpart dynamics. We demonstrate our approach in a numerically accurate manner through solvable examples. We further apply the method to investigate the role of noise on tumor heterogeneity in a 38-dimensional network model for prostate cancer, and provide a new strategy on controlling cell populations by manipulating noise strength.
Urothelial cancer proteomics provides both prognostic and functional information
Authors: de Velasco Guillermo , Trilla-Fuertes Lucia , Gamez-Pozo Angelo , Urbanowicz Maria , Ruiz-Ares Gustavo , Sepúlveda Juan M. , Prado-Vazquez Guillermo , Arevalillo Jorge M. , Zapater-Moros Andrea , Navarro Hilario , Lopez-Vacas Rocio , Manneh Ray , Otero Irene , Villacampa Felipe , Paramio Jesus M. , Vara Juan Angel Fresno , Castellano Daniel 
Published: November 2017

AbstractTraditionally, bladder cancer has been classified based on histology features. Recently, some works have proposed a molecular classification of invasive bladder tumors. To determine whether proteomics can define molecular subtypes of muscle invasive urothelial cancer (MIUC) and allow evaluating the status of biological processes and its clinical value. 58 MIUC patients who underwent curative surgical resection at our institution between 2006 and 2012 were included. Proteome was evaluated by high-throughput proteomics in routinely archive FFPE tumor tissue. New molecular subgroups were defined. Functional structure and individual proteins prognostic value were evaluated and correlated with clinicopathologic parameters. 1,453 proteins were quantified, leading to two MIUC molecular subgroups. A protein-based functional structure was defined, including several nodes with specific biological activity. The functional structure showed differences between subtypes in metabolism, focal adhesion, RNA and splicing nodes. Focal adhesion node has prognostic value in the whole population. A 6-protein prognostic signature, associated with higher risk of relapse (5 year DFS 70% versus 20%) was defined. Additionally, we identified two MIUC subtypes groups. Prognostic information provided by pathologic characteristics is not enough to understand MIUC behavior. Proteomics analysis may enhance our understanding of prognostic and classification. These findings can lead to improving diagnosis and treatment selection in these patients.
PNPLA3 variant and portal/periportal histological pattern in patients with biopsy-proven non-alcoholic fatty liver disease: a possible role for oxidative stress
Authors: Carpino Guido , Pastori Daniele , Baratta Francesco , Overi Diletta , Labbadia Giancarlo , Polimeni Licia , Di Costanzo Alessia , Pannitteri Gaetano , Carnevale Roberto , Del Ben Maria , Arca Marcello , Violi Francesco , Angelico Francesco , Gaudio Eugenio 
Published: November 2017

AbstractPathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by predisposing genetic variations, dysmetabolism, systemic oxidative stress, and local cellular and molecular cross-talks. Patatin-like phospholipase domain containing 3 (PNPLA3) gene I148M variant is a known determinant of NAFLD. Aims were to evaluate whether PNPLA3 I148M variant was associated with a specific histological pattern, hepatic stem/progenitor cell (HpSC) niche activation and serum oxidative stress markers. Liver biopsies were obtained from 54 NAFLD patients. The activation of HpSC compartment was evaluated by the extension of ductular reaction (DR); hepatic stellate cells, myofibroblasts (MFs), and macrophages were evaluated by immunohistochemistry. Systemic oxidative stress was assessed measuring serum levels of soluble NOX2-derived peptide (sNOX2-dp) and 8-isoprostaglandin F2α (8-iso-PGF2α). PNPLA3 carriers showed higher steatosis, portal inflammation and HpSC niche activation compared to wild-type patients. DR was correlated with NAFLD activity score (NAS) and fibrosis score. Serum 8-iso-PGF2α were significantly higher in I148M carriers compared to non-carriers and were correlated with DR and portal inflammation. sNox2-dp was correlated with NAS and with HpSC niche activation. In conclusion, NAFLD patients carrying PNPLA3 I148M are characterized by a prominent activation of HpSC niche which is associated with a more aggressive histological pattern (portal fibrogenesis) and increased oxidative stress.