bluuebunny/crossref_metadata_2025_split huggingface dataset:
miRNA-mediated TUSC3 deficiency enhances UPR and ERAD to promote metastatic potential of NSCLC
Authors: Jeon Young-Jun , Kim Taewan , Park Dongju , Nuovo Gerard J. , Rhee Siyeon , Joshi Pooja , Lee Bum-Kyu , Jeong Johan , Suh Sung-suk , Grotzke Jeff E. , Kim Sung-Hak , Song Jieun , Sim Hosung , Kim Yonghwan , Peng Yong , Jeong Youngtae , Garofalo Michela , Zanesi Nicola , Kim Jonghwan , Liang Guang , Nakano Ichiro , Cresswell Peter , Nana-Sinkam Patrick , Cui Ri , Croce Carlo M. 
Published: November 2018

AbstractNon-small cell lung carcinoma (NSCLC) is leading cause of cancer-related deaths in the world. The Tumor Suppressor Candidate 3 (TUSC3) at chromosome 8p22 known to be frequently deleted in cancer is often found to be deleted in advanced stage of solid tumors. However, the role of TUSC3 still remains controversial in lung cancer and context-dependent in several cancers. Here we propose that miR-224/-520c-dependent TUSC3 deficiency enhances the metastatic potential of NSCLC through the alteration of three unfolded protein response pathways and HRD1-dependent ERAD. ATF6α-dependent UPR is enhanced whereas the affinity of HRD1 to its substrates, PERK, IRE1α and p53 is weakened. Consequently, the alteration of UPRs and the suppressed p53-NM23H1/2 pathway by TUSC3 deficiency is ultimately responsible for enhancing metastatic potential of lung cancer. These findings provide mechanistic insight of unrecognized roles of TUSC3 in cancer progression and the oncogenic role of HRD1-dependent ERAD in cancer metastasis.
Nanoribbons self-assembled from short peptides demonstrate the formation of polar zippers between β-sheets
Authors: Wang Meng , Wang Jiqian , Zhou Peng , Deng Jing , Zhao Yurong , Sun Yawei , Yang Wei , Wang Dong , Li Zongyi , Hu Xuzhi , King Stephen M. , Rogers Sarah E. , Cox Henry , Waigh Thomas A. , Yang Jun , Lu Jian Ren , Xu Hai 
Published: November 2018

AbstractPeptide self-assembly is a hierarchical process, often starting with the formation of α-helices, β-sheets or β-hairpins. However, how the secondary structures undergo further assembly to form higher-order architectures remains largely unexplored. The polar zipper originally proposed by Perutz is formed between neighboring β-strands of poly-glutamine via their side-chain hydrogen bonding and helps to stabilize the sheet. By rational design of short amphiphilic peptides and their self-assembly, here we demonstrate the formation of polar zippers between neighboring β-sheets rather than between β-strands within a sheet, which in turn intermesh the β-sheets into wide and flat ribbons. Such a super-secondary structural template based on well-defined hydrogen bonds could offer an agile route for the construction of distinctive nanostructures and nanomaterials beyond β-sheets.
A monoclinic polymorph of sodium birnessite for ultrafast and ultrastable sodium ion storage
Authors: Xia Hui , Zhu Xiaohui , Liu Jizi , Liu Qi , Lan Si , Zhang Qinghua , Liu Xinyu , Seo Joon Kyo , Chen Tingting , Gu Lin , Meng Ying Shirley 
Published: November 2018

AbstractSodium transition metal oxides with layered structures are attractive cathode materials for sodium-ion batteries due to their large theoretical specific capacities. However, these layered oxides suffer from poor cyclability and low rate performance because of structural instability and sluggish electrode kinetics. In the present work, we show the sodiation reaction of Mn3O4 to yield crystal water free NaMnO2−y−δ(OH)2y, a monoclinic polymorph of sodium birnessite bearing Na/Mn(OH)8 hexahedra and Na/MnO6 octahedra. With the new polymorph, NaMnO2−y−δ(OH)2y exhibits an enlarged interlayer distance of about 7 Å, which is in favor of fast sodium ion migration and good structural stability. In combination of the favorable nanosheet morphology, NaMn2−y−δ(OH)2y cathode delivers large specific capacity up to 211.9 mAh g–1, excellent cycle performance (94.6% capacity retention after 1000 cycles), and outstanding rate capability (156.0 mAh g–1 at 50 C). This study demonstrates an effective approach in tailoring the structural and electrochemical properties of birnessite towards superior cathode performance in sodium-ion batteries.
Human preprocalcitonin self-antigen generates TAP-dependent and -independent epitopes triggering optimised T-cell responses toward immune-escaped tumours
Authors: Durgeau Aurélie , Virk Yasemin , Gros Gwendoline , Voilin Elodie , Corgnac Stéphanie , Djenidi Fayçal , Salmon Jérôme , Adam Julien , de Montpréville Vincent , Validire Pierre , Ferrone Soldano , Chouaib Salem , Eggermont Alexander , Soria Jean-Charles , Lemonnier François , Tartour Eric , Chaput Nathalie , Besse Benjamin , Mami-Chouaib Fathia 
Published: November 2018

AbstractTumours often evade CD8 T-cell immunity by downregulating TAP. T-cell epitopes associated with impaired peptide processing are immunogenic non-mutated neoantigens that emerge during tumour immune evasion. The preprocalcitonin (ppCT)16–25neoepitope belongs to this category of antigens. Here we show that most human lung tumours display altered expression of TAP and frequently express ppCT self-antigen. We also show that ppCT includes HLA-A2-restricted epitopes that are processed by TAP-independent and -dependent pathways. Processing occurs in either the endoplasmic reticulum, by signal peptidase and signal peptide peptidase, or in the cytosol after release of a signal peptide precursor or retrotranslocation of a procalcitonin substrate by endoplasmic-reticulum-associated degradation. Remarkably, ppCT peptide-based immunotherapy induces efficient T-cell responses toward antigen processing and presenting machinery-impaired tumours transplanted into HLA-A*0201-transgenic mice and in NOD-scid-Il2rγnullmice adoptively transferred with human PBMC. Thus, ppCT-specific T lymphocytes are promising effectors for treatment of tumours that have escaped immune recognition.
Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential
Authors: Wampach Linda , Heintz-Buschart Anna , Fritz Joëlle V. , Ramiro-Garcia Javier , Habier Janine , Herold Malte , Narayanasamy Shaman , Kaysen Anne , Hogan Angela H. , Bindl Lutz , Bottu Jean , Halder Rashi , Sjöqvist Conny , May Patrick , Andersson Anders F. , de Beaufort Carine , Wilmes Paul 
Published: November 2018

AbstractThe rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclear whether disruption of mother-to-neonate transmission of microbiota through CSD occurs and whether it affects human physiology. Here we perform metagenomic analysis of earliest gut microbial community structures and functions. We identify differences in encoded functions between microbiomes of vaginally delivered (VD) and CSD neonates. Several functional pathways are over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis. We link these enriched functions to individual-specific strains, which are transmitted from mothers to neonates in case of VD. The stimulation of primary human immune cells with LPS isolated from early stool samples of VD neonates results in higher levels of tumour necrosis factor (TNF-α) and interleukin 18 (IL-18). Accordingly, the observed levels of TNF-α and IL-18 in neonatal blood plasma are higher after VD. Taken together, our results support that CSD disrupts mother-to-neonate transmission of specific microbial strains, linked functional repertoires and immune-stimulatory potential during a critical window for neonatal immune system priming.
Cytoplasmic LIF reprograms invasive mode to enhance NPC dissemination through modulating YAP1-FAK/PXN signaling
Authors: Liu Shu-Chen , Hsu Tien , Chang Yu-Sun , Chung An-Ko , Jiang Shih Sheng , OuYang Chun-Nan , Yuh Chiou-Hwa , Hsueh Chuen , Liu Ya-Ping , Tsang Ngan-Ming 
Published: November 2018

AbstractMetastasis remains a clinically unsolved issue in nasopharyngeal carcinoma. Here, we report that higher levels of cytoplasmic leukemia inhibitory factor (LIF) and LIF receptor are correlated with poorer metastasis/recurrence-free survival. Further, single nucleotide variations and signal peptide mutation of LIF are identified in NPC. Cytoplasmic LIF reprograms the invasive mode from collective to mesenchymal migration via acquisition of EMT and invadopodia-associated characteristics. Higher cytoplasmic LIF enhances cancer vascular dissemination and local invasion mechanistically through modulation of YAP1-FAK/PXN signaling. Immunohistochemical analyses of NPC biopsies reveal a positive correlation of cytoplasmic LIF expression with focal adhesion kinases. Pharmaceutical intervention with AZD0530 markedly reverses LIF-mediated cancer dissemination and local invasion through promotion of cytoplasmic accumulation of YAP1 and suppression of focal adhesion kinases. Given the significant role of LIF/YAP1-focal adhesion signaling in cancer dissemination, targeting of this pathway presents a promising opportunity to block metastasis.
Subcellular connectomic analyses of energy networks in striated muscle
Authors: Bleck Christopher K. E. , Kim Yuho , Willingham T. Bradley , Glancy Brian 
Published: November 2018

AbstractMapping biological circuit connectivity has revolutionized our understanding of structure-function relationships. Although connectomic analyses have primarily focused on neural systems, electrical connectivity within muscle mitochondrial networks was recently demonstrated to provide a rapid mechanism for cellular energy distribution. However, tools to evaluate organelle connectivity with high spatial fidelity within single cells are currently lacking. Here, we developed a framework to quantitatively assess mitochondrial network connectivity and interactions with cellular sites of energy storage, utilization, and calcium cycling in cardiac, oxidative, and glycolytic muscle. We demonstrate that mitochondrial network configuration, individual mitochondrial size and shape, and the junctions connecting mitochondria within each network are consistent with the differing contraction demands of each muscle type. Moreover, mitochondria-lipid droplet interaction analyses suggest that individual mitochondria within networks may play specialized roles regarding energy distribution and calcium cycling within the cell and reveal the power of connectomic analyses of organelle interactions within single cells.
Nitrogen physiology of contrasting genotypes of Chenopodium quinoa Willd. (Amaranthaceae)
Authors: Bascuñán-Godoy Luisa , Sanhueza Carolina , Pinto Katherine , Cifuentes Leonardo , Reguera María , Briones Vilbett , Zurita-Silva Andrés , Álvarez Rodrigo , Morales Andrea , Silva Herman 
Published: November 2018

AbstractQuinoa has been highlighted as a promising crop to sustain food security. The selection of physiological traits that allow identification genotypes with high Nitrogen use efficiency (NUE) is a key factor to increase Quinoa cultivation. In order to unveil the underpinning mechanisms for N-stress tolerance in Quinoa, three genotypes with similar phenology, but different NUE were developed under high (HN) or low (LN) nitrogen conditions. N metabolism processes and photosynthetic performance were studied after anthesis and in correlation with productivity to identify principal traits related to NUE. We found that protein content, net photosynthesis and leaf dry-mass were determinant attributes for yield at both HN and LN conditions. Contrastingly, the enhancement of N related metabolites ($${{\rm{NH}}}_{4}^{+}$$

NH

4

+

, proline, betacyanins) and processes related with re-assimilation of $${{\rm{NH}}}_{4}^{+}$$

NH

4

+

, including an increment of glutamine synthetase activity and up-regulation of CqAMT1,1 transporter expression in leaves, were negatively correlated with grain yield at both N conditions. Biochemical aspects of photosynthesis and root biomass were traits exclusively associated with grain yield at LN. The impact of N supply on seed quality is discussed. These results provide new insights towards the understanding the N metabolism of Quinoa.
Episodic zircon age spectra mimic fluctuations in subduction
Authors: Domeier Mathew , Magni Valentina , Hounslow Mark W. , Torsvik Trond H. 
Published: November 2018

AbstractDecades of geochronological work have shown the temporal distribution of zircon ages to be episodic on billion-year timescales and seemingly coincident with the lifecycle of supercontinents, but the physical processes behind this episodicity remain contentious. The dominant, end-member models of fluctuating magmatic productivity versus selective preservation of zircon during times of continental assembly have important and very different implications for long-term, global-scale phenomena, including the history of crustal growth, the initiation and evolution of plate tectonics, and the tempo of mantle outgassing over billions of years. Consideration of this episodicity has largely focused on the Precambrian, but here we analyze a large collection of Phanerozoic zircon ages in the context of global, full-plate tectonic models that extend back to the mid-Paleozoic. We scrutinize two long-lived and relatively simple active margins, and show that along both, a relationship between the regional subduction flux and zircon age distribution is evident. In both cases, zircon age peaks correspond to intervals of high subduction flux with a ~10–30 Ma time lag (zircons trailing subduction), illuminating a possibly intrinsic delay in the subduction-related magmatic system. We also show that subduction fluxes provide a stronger correlation to zircon age distributions than subduction lengths do, implying that convergence rates play a significant role in regulating the volume of melting in subduction-related magmatic systems, and thus crustal growth.
Causes of volcanic unrest at Mt. Spurr in 2004–2005 inferred from repeated tomography
Authors: Koulakov I. , Smirnov S. Z. , Gladkov V. , Kasatkina E. , West M. , El Khrepy S. , Al-Arifi N. 
Published: November 2018

AbstractMt. Spurr is the largest active volcano in Alaska of high explosive potential. The most recent activity, including two recent magmatic eruptions in 1953 and 1992, has occurred via the flanking Crater Peak. From 2004 to 2006, strong seismicity, gas flux, and heating were observed in the summit area, which had remained inactive for more than 5 Ka. To understand the cause of this reactivation, we performed repeated tomography inversions that clearly imaged the magma reservoir beneath Mt. Spurr and showed temporal changes in its shape and intensity. During the two years preceding the unrest, we observed ascension of the upper limit of the reservoir-related anomaly from a depth of 5 to 3 km below the surface, accompanied by strong seismicity. During the following years, the shape of the anomaly remained unchanged, but its intensity weakened. These observations may indicate the release of fluids from the ductile reservoir and fast upward ascent through the brittle cover that caused intensive seismicity and gas flux during the unrest from 2004 to 2006. The origin of this zone will possibly cause a resumption of explosive eruptions in the summit area of Mt. Spurr.
Computational Investigation of the Morphology, Efficiency, and Properties of Silver Nano Wires Networks in Transparent Conductive Film
Authors: Han Fei , Maloth Thirupathi , Lubineau Gilles , Yaldiz Recep , Tevtia Amit 
Published: November 2018

AbstractRandom networks of silver nano wires have been considered for use in transparent conductive films as an alternative to Indium Tin Oxide (ITO), which is unsuitable for flexible devices. However, the random distribution of nano wires makes such conductive films non-uniform. As electrical conductivity is achieved through a percolation process, understanding the scale-dependency of the macroscopic properties (like electrical conductivity) and the exact efficiency of the network (the proportion of nano wires that participate in electrical conduction) is essential for optimizing the design. In this paper, we propose a computational method for identifying the representative volume element (RVE) of nano wire networks. This defines the minimum pixel size in devices using such transparent electrodes. The RVE is used to compute the macroscopic properties of films and to quantify the electrically conducting efficiency of networks. Then, the sheet resistance and transparency of networks are calculated based on the predicted RVEs, in order to analyze the effects of nano wire networks on the electrical and optical properties of conductive films. The results presented in this paper provide insights that help optimizing random nano wire networks in transparent conductive films for achieving better efficiencies.
Magnetotransport and conductivity mechanisms in Cu2ZnSnxGe1−xS4 single crystals
Authors: Lähderanta Erkki , Hajdeu-Chicarosh Elena , Guc Maxim , Shakhov Mikhail A. , Zakharchuk Ivan , Bodnar Ivan V. , Arushanov Ernest , Lisunov Konstantin G. 
Published: November 2018

AbstractResistivity, ρ(T), and magnetoresistance (MR) are investigated in the Cu2ZnSnxGe1−xS4 single crystals, obtained by the chemical vapor transport method, between x = 0–0.70, in the temperature range of T ~ 50–300 K in pulsed magnetic field of B up to 20 T. The Mott variable-range hopping (VRH) conductivity is observed within broad temperature intervals, lying inside that of T ~ 80–180 K for different x. The nearest-neighbor hopping conductivity and the charge transfer, connected to activation of holes into the delocalized states of the acceptor band, are identified above and below the Mott VRH conduction domain, respectively. The microscopic electronic parameters, including width of the acceptor band, the localization radius and the density of the localized states at the Fermi level, as well as the acceptor concentration and the critical concentration of the metal-insulator transition, are obtained with the analysis of the ρ(T) and MR data. All the parameters above exhibit extremums near x = 0.13, which are attributable mainly to the transition from the stannite crystal structure at x = 0 to the kesterite-like structure near x = 0.13. The detailed analysis of the activation energy in the low-temperature interval permitted estimations of contributions from different crystal phases of the border compounds into the alloy structure at different compositions.
The central exons of the human MUC2 and MUC6 mucins are highly repetitive and variable in sequence between individuals
Authors: Svensson Frida , Lang Tiange , Johansson Malin E. V. , Hansson Gunnar C. 
Published: November 2018

AbstractThe DNA sequence of the two human mucin genes MUC2 and MUC6 have not been completely resolved due to the repetitive nature of their central exon coding for Proline, Threonine and Serine rich sequences. The exact nucleotide sequence of these exons has remained unknown for a long time due to limitations in traditional sequencing techniques. These are still very poorly covered in new whole genome sequencing projects with the corresponding protein sequences partly missing. We used a BAC clone containing both these genes and third generation sequencing technology, SMRT sequencing, to obtain the full-length contiguous MUC2 and MUC6 tandem repeat sequences. The new sequences span the entire repeat regions with good coverage revealing their length, variation in repeat sequences and their internal organization. The sequences obtained were used to compare with available sequences from whole genome sequencing projects indicating variation in number of repeats and their internal organization between individuals. The lack of these sequences has limited the association of genetic alterations with disease. The full sequences of these mucins will now allow such studies, which could be of importance for inflammatory bowel diseases for MUC2 and gastric ulcer diseases for MUC6 where deficient mucus protection is assumed to play an important role.
Improved Kerogen Models for Determining Thermal Maturity and Hydrocarbon Potential of Shale
Authors: Agrawal Vikas , Sharma Shikha 
Published: November 2018

AbstractKerogen is the insoluble component of organic-rich shales that controls the type and amount of hydrocarbons generated in conventional and unconventional reservoirs. Significant progress has recently been made in developing structural models of kerogen. However, there is still a large gap in understanding the evolution of the molecular components of kerogen with thermal maturation and their hydrocarbon (HC) generative potential. Here, we determine the variations in different molecular fragments of kerogen from a Marcellus Shale maturity series (with VRo ranging from 0.8 to 3) using quantitative 13C MultiCP/MAS NMR and MultiCP NMR/DD (dipolar dephasing). These molecular variations provide insight into the (1) evolution of the molecular structure of kerogen with increasing thermal maturity and, (2) the primary molecular contributors to HC generation. Our results also indicate that old model equations based on structural parameters of kerogen underestimate the thermal maturity and overestimate the HC generation potential of Marcellus Shale samples. This could primarily be due to the fact that the kerogen samples used to reconstruct old models were mostly derived from immature shales (VRo <1) acquired from different basins with varying depositional environments. We utilized the kerogen molecular parameters determined from the Marcellus maturity series samples to develop improved models for determining thermal maturity and HC potential of Marcellus Shale. The models generated in this study could also potentially be applied to other shales of similar maturity range and paleo-depositional environments.
Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing
Authors: Sun Naidi , Ning Bo , Hansson Kenny M. , Bruce Anthony C. , Seaman Scott A. , Zhang Chenchu , Rikard Michaela , DeRosa Christopher A. , Fraser Cassandra L. , Wågberg Maria , Fritsche-Danielson Regina , Wikström Johannes , Chien Kenneth R. , Lundahl Anna , Hölttä Mikko , Carlsson Leif G. , Peirce Shayn M. , Hu Song 
Published: November 2018

AbstractCapable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood. Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. Using multi-parametric photoacoustic microscopy, we show that intradermal injection of AZD8601 formulated in a biocompatible vehicle results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.