bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annexin A5 regulates hepatocarcinoma malignancy via CRKI/II-DOCK180-RAC1 integrin and MEK-ERK pathways
Authors: Sun Xujuan , Liu Shuqing , Wang Jinxia , Wei Bin , Guo Chunmei , Chen Chen , Sun Ming-Zhong 
Published: May 2018

AbstractAs a calcium-dependent phospholipid binding annexin protein, annexin A5 (Anxa5) links to the progression, metastasis, survival, and prognosis of a variety of cancers. Current work showed ANXA5 overexpression was positively correlated with the upregulations of CRKI/II and RAC1 in hepatocarcinoma (HCC) patients’ tissues, which potentially enhanced the clinical progression and lymphatic metastasis of HCC. The role and action mechanism of ANXA5 in hepatocarcinoma was then investigated using a hepatocarcinoma Hca-P cell line, an ideal and well-established murine cell model with 100% inducible tumorigenicity of implanted mice with low (~25%) lymph node metastatic (LNM) rate. In vitro evidences indicated ANXA5 stable knockdown resulted in decreased proliferation, migration, invasion and adhesion to lymph node (LN), and increased intercellular cohesion behaviors of hepatocarcinoma Hca-P cells. Consistently, stable ANXA5 knockdown led to reduced in vivo tumorigenicity and malignancy, LNM rate and level potentials of Hca-P- transplanted mice via inhibiting CD34 and VEGF3. The levels of CRKI/II and RAC1 were reduced in tumor tissues from mice transplanted with Hca-P cells with stable ANXA5 knockdown. Molecular action investigation further showed ANXA5 downregulation apparently suppressed the expressions of molecules CRKI/II, DOCK180, RAC1 in integrin pathway, p-MEK, p-ERK, c-Myc, and MMP-9 in MEK- ERK pathway together with VIMINTIN in Hca-P cells in appropriate to knockdown extent. Collectively, Anxa5 was able to mediate HCC carcinogenesis via integrin and MEK-ERK pathways. It is of potential use in the research and treatment of HCC.
Protein disorder–order interplay to guide the growth of hierarchical mineralized structures
Authors: Elsharkawy Sherif , Al-Jawad Maisoon , Pantano Maria F. , Tejeda-Montes Esther , Mehta Khushbu , Jamal Hasan , Agarwal Shweta , Shuturminska Kseniya , Rice Alistair , Tarakina Nadezda V. , Wilson Rory M. , Bushby Andy J. , Alonso Matilde , Rodriguez-Cabello Jose C. , Barbieri Ettore , del Río Hernández Armando , Stevens Molly M. , Pugno Nicola M. , Anderson Paul , Mata Alvaro 
Published: May 2018

AbstractA major goal in materials science is to develop bioinspired functional materials based on the precise control of molecular building blocks across length scales. Here we report a protein-mediated mineralization process that takes advantage of disorder–order interplay using elastin-like recombinamers to program organic–inorganic interactions into hierarchically ordered mineralized structures. The materials comprise elongated apatite nanocrystals that are aligned and organized into microscopic prisms, which grow together into spherulite-like structures hundreds of micrometers in diameter that come together to fill macroscopic areas. The structures can be grown over large uneven surfaces and native tissues as acid-resistant membranes or coatings with tuneable hierarchy, stiffness, and hardness. Our study represents a potential strategy for complex materials design that may open opportunities for hard tissue repair and provide insights into the role of molecular disorder in human physiology and pathology.
Cellular conditions of weakly chelated magnesium ions strongly promote RNA stability and catalysis
Authors: Yamagami Ryota , Bingaman Jamie L. , Frankel Erica A. , Bevilacqua Philip C. 
Published: May 2018

AbstractMost RNA folding studies have been performed under non-physiological conditions of high concentrations (≥10 mM) of Mg2+free, while actual cellular concentrations of Mg2+free are only ~1 mM in a background of greater than 50 mM Mg2+total. To uncover cellular behavior of RNA, we devised cytoplasm mimic systems that include biological concentrations of amino acids, which weakly chelate Mg2+. Amino acid-chelated Mg2+ (aaCM) of ~15 mM dramatically increases RNA folding and prevents RNA degradation. Furthermore, aaCM enhance self-cleavage of several different ribozymes, up to 100,000-fold at Mg2+free of just 0.5 mM, indirectly through RNA compaction. Other metabolites that weakly chelate magnesium offer similar beneficial effects, which implies chelated magnesium may enhance RNA function in the cell in the same way. Overall, these results indicate that the states of Mg2+ should not be limited to free and bound only, as weakly bound Mg2+ strongly promotes RNA function under cellular conditions.
Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter
Authors: Yang Ruili , Yu Tingting , Kou Xiaoxing , Gao Xiang , Chen Chider , Liu Dawei , Zhou Yanheng , Shi Songtao 
Published: May 2018

AbstractTen-eleven translocation (Tet) family-mediated DNA oxidation represents an epigenetic modification capable of converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), which regulates various biological processes. However, it is unknown whether Tet family affects mesenchymal stem cells (MSCs) or the skeletal system. Here we show that depletion of Tet1 and Tet2 results in impaired self-renewal and differentiation of bone marrow MSCs (BMMSCs) and a significant osteopenia phenotype. Tet1 and Tet2 deficiency reduces demethylation of the P2rX7 promoter and downregulates exosome release, leading to intracellular accumulation of miR-297a-5p, miR-297b-5p, and miR-297c-5p. These miRNAs inhibit Runx2 signaling to impair BMMSC function. We show that overexpression of P2rX7 rescues the impaired BMMSCs and osteoporotic phenotype in Tet1 and Tet2 double knockout mice. These results indicate that Tet1 and Tet2 play a critical role in maintaining BMMSC and bone homeostasis through demethylation of P2rX7 to control exosome and miRNA release. This Tet/P2rX7/Runx2 cascade may serve as a target for the development of novel therapies for osteopenia disorders.
Total synthesis of cyrneines A–B and glaucopine C
Authors: Wu Guo-Jie , Zhang Yuan-He , Tan Dong-Xing , Han Fu-She 
Published: May 2018

AbstractThe cyrneine diterpenoids represent a structurally intriguing subfamily of cyathane diterpenoids and could significantly induce neurite outgrowth. Therefore, the efficient synthesis of these natural products is of great importance. Herein, we present a route for the collective synthesis of cyrneines A, B, and glaucopine C. As the key precursor, the 5-6-6-tricyclic scaffold is efficiently constructed by employing a mild Suzuki coupling of heavily substituted nonactivated cyclopentenyl triflate and a chelation-controlled regiospecific Friedel-Crafts cyclization as key transformations. The stereoselective installation of the all-carbon quaternary center at C6 ring junction of the tricycle is achieved via Birch reductive methylation. Subsequently, a carbenoid-mediated ring expansion furnishes the essential 5-6-7-tricyclic core. Finally, manipulation of this core by several appropriately orchestrated conversions accomplishes a more step-economic synthesis of cyrneine A (20 steps), and the first synthesis of cyrneine B (24 steps) and glaucopine C (23 steps).
Dynamic structural states of ClpB involved in its disaggregation function
Authors: Uchihashi Takayuki , Watanabe Yo-hei , Nakazaki Yosuke , Yamasaki Takashi , Watanabe Hiroki , Maruno Takahiro , Ishii Kentaro , Uchiyama Susumu , Song Chihong , Murata Kazuyoshi , Iino Ryota , Ando Toshio 
Published: May 2018

AbstractThe ATP-dependent bacterial protein disaggregation machine, ClpB belonging to the AAA+ superfamily, refolds toxic protein aggregates into the native state in cooperation with the cognate Hsp70 partner. The ring-shaped hexamers of ClpB unfold and thread its protein substrate through the central pore. However, their function-related structural dynamics has remained elusive. Here we directly visualize ClpB using high-speed atomic force microscopy (HS-AFM) to gain a mechanistic insight into its disaggregation function. The HS-AFM movies demonstrate massive conformational changes of the hexameric ring during ATP hydrolysis, from a round ring to a spiral and even to a pair of twisted half-spirals. HS-AFM observations of Walker-motif mutants unveil crucial roles of ATP binding and hydrolysis in the oligomer formation and structural dynamics. Furthermore, repressed and hyperactive mutations result in significantly different oligomeric forms. These results provide a comprehensive view for the ATP-driven oligomeric-state transitions that enable ClpB to disentangle protein aggregates.
Species traits and network structure predict the success and impacts of pollinator invasions
Authors: Valdovinos Fernanda S. , Berlow Eric L. , Moisset de Espanés Pablo , Ramos-Jiliberto Rodrigo , Vázquez Diego P. , Martinez Neo D. 
Published: May 2018

AbstractSpecies invasions constitute a major and poorly understood threat to plant–pollinator systems. General theory predicting which factors drive species invasion success and subsequent effects on native ecosystems is particularly lacking. We address this problem using a consumer–resource model of adaptive behavior and population dynamics to evaluate the invasion success of alien pollinators into plant–pollinator networks and their impact on native species. We introduce pollinator species with different foraging traits into network models with different levels of species richness, connectance, and nestedness. Among 31 factors tested, including network and alien properties, we find that aliens with high foraging efficiency are the most successful invaders. Networks exhibiting high alien–native diet overlap, fraction of alien-visited plant species, most-generalist plant connectivity, and number of specialist pollinator species are the most impacted by invaders. Our results mimic several disparate observations conducted in the field and potentially elucidate the mechanisms responsible for their variability.
Recovery of genomes from metagenomes via a dereplication, aggregation and scoring strategy
Authors: Sieber Christian M. K. , Probst Alexander J. , Sharrar Allison , Thomas Brian C. , Hess Matthias , Tringe Susannah G. , Banfield Jillian F. 
Published: May 2018

AbstractMicrobial communities are critical to ecosystem function. A key objective of metagenomic studies is to analyse organism-specific metabolic pathways and reconstruct community interaction networks. This requires accurate assignment of assembled genome fragments to genomes. Existing binning methods often fail to reconstruct a reasonable number of genomes and report many bins of low quality and completeness. Furthermore, the performance of existing algorithms varies between samples and biotopes. Here, we present a dereplication, aggregation and scoring strategy, DAS Tool, that combines the strengths of a flexible set of established binning algorithms. DAS Tool applied to a constructed community generated more accurate bins than any automated method. Indeed, when applied to environmental and host-associated samples of different complexity, DAS Tool recovered substantially more near-complete genomes, including previously unreported lineages, than any single binning method alone. The ability to reconstruct many near-complete genomes from metagenomics data will greatly advance genome-centric analyses of ecosystems.
Japanese GWAS identifies variants for bust-size, dysmenorrhea, and menstrual fever that are eQTLs for relevant protein-coding or long non-coding RNAs
Authors: Hirata Tetsuya , Koga Kaori , Johnson Todd A. , Morino Ryoko , Nakazono Kazuyuki , Kamitsuji Shigeo , Akita Masanori , Kawajiri Maiko , Kami Azusa , Hoshi Yuria , Tada Asami , Ishikawa Kenichi , Hine Maaya , Kobayashi Miki , Kurume Nami , Fujii Tomoyuki , Kamatani Naoyuki , Osuga Yutaka 
Published: May 2018

AbstractTraits related to primary and secondary sexual characteristics greatly impact females during puberty and day-to-day adult life. Therefore, we performed a GWAS analysis of 11,348 Japanese female volunteers and 22 gynecology-related phenotypic variables, and identified significant associations for bust-size, menstrual pain (dysmenorrhea) severity, and menstrual fever. Bust-size analysis identified significant association signals in CCDC170-ESR1 (rs6557160; P = 1.7 × 10−16) and KCNU1-ZNF703 (rs146992477; P = 6.2 × 10−9) and found that one-third of known European-ancestry associations were also present in Japanese. eQTL data points to CCDC170 and ZNF703 as those signals’ functional targets. For menstrual fever, we identified a novel association in OPRM1 (rs17181171; P = 2.0 × 10−8), for which top variants were eQTLs in multiple tissues. A known dysmenorrhea signal near NGF replicated in our data (rs12030576; P = 1.1 × 10−19) and was associated with RP4-663N10.1 expression, a putative lncRNA enhancer of NGF, while a novel dysmenorrhea signal in the IL1 locus (rs80111889; P = 1.9 × 10−16) contained SNPs previously associated with endometriosis, and GWAS SNPs were most significantly associated with IL1A expression. By combining regional imputation with colocalization analysis of GWAS/eQTL signals along with integrated annotation with epigenomic data, this study further refines the sets of candidate causal variants and target genes for these known and novel gynecology-related trait loci.
Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts
Authors: Elgart S. Robin , Little Mark P. , Chappell Lori J. , Milder Cato M. , Shavers Mark R. , Huff Janice L. , Patel Zarana S. 
Published: May 2018

Abstract
Understanding space radiation health effects is critical due to potential increased morbidity and mortality following spaceflight. We evaluated whether there is evidence for excess cardiovascular disease or cancer mortality in early NASA astronauts and if a correlation exists between space radiation exposure and mortality. Astronauts selected from 1959–1969 were included and followed until death or February 2017, with 39 of 73 individuals still alive at that time. Calculated standardized mortality rates for tested outcomes were significantly below U.S. white male population rates, including all-cardiovascular disease (n = 7, SMR = 33; 95% CI, 14–65) and all-cancer (n = 7, SMR = 43; 95% CI, 18–83), as anticipated in a healthy worker population. Space radiation doses for cohort members ranged from 0–78 mGy. No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation. Statistical power of the logistic regression was <6%, remaining <12% even when expected risk level or observed deaths were assumed to be 10 times higher than currently reported. While no excess radiation-associated cardiovascular or cancer mortality risk was observed, findings must be tempered by the statistical limitations of this cohort; notwithstanding, this small unique cohort provides a foundation for assessment of astronaut health.
Changing flood frequencies under opposing late Pleistocene eastern Mediterranean climates
Authors: Ben Dor Yoav , Armon Moshe , Ahlborn Marieke , Morin Efrat , Erel Yigal , Brauer Achim , Schwab Markus Julius , Tjallingii Rik , Enzel Yehouda 
Published: May 2018

AbstractFloods comprise a dominant hydroclimatic phenomenon in aridlands with significant implications for humans, infrastructure, and landscape evolution worldwide. The study of short-term hydroclimatic variability, such as floods, and its forecasting for episodes of changing climate therefore poses a dominant challenge for the scientific community, and predominantly relies on modeling. Testing the capabilities of climate models to properly describe past and forecast future short-term hydroclimatic phenomena such as floods requires verification against suitable geological archives. However, determining flood frequency during changing climate is rarely achieved, because modern and paleoflood records, especially in arid regions, are often too short or discontinuous. Thus, coeval independent climate reconstructions and paleoflood records are required to further understand the impact of climate change on flood generation. Dead Sea lake levels reflect the mean centennial-millennial hydrological budget in the eastern Mediterranean. In contrast, floods in the large watersheds draining directly into the Dead Sea, are linked to short-term synoptic circulation patterns reflecting hydroclimatic variability. These two very different records are combined in this study to resolve flood frequency during opposing mean climates. Two 700-year-long, seasonally-resolved flood time series constructed from late Pleistocene Dead Sea varved sediments, coeval with significant Dead Sea lake level variations are reported. These series demonstrate that episodes of rising lake levels are characterized by higher frequency of floods, shorter intervals between years of multiple floods, and asignificantly larger number of years that experienced multiple floods. In addition, floods cluster into intervals of intense flooding, characterized by 75% and 20% increased frequency above their respective background frequencies during rising and falling lake-levels, respectively. Mean centennial precipitation in the eastern Mediterranean is therefore coupled with drastic changes in flood frequencies. These drastic changes in flood frequencies are linked to changes in the track, depth, and frequency of mid-latitude eastern Mediterranean cyclones, determining mean climatology resulting in wetter and drier regional climatic episodes.
Ameliorative effect of Sedum sarmentosum Bunge extract on Tilapia fatty liver via the PPAR and P53 signaling pathway
Authors: Huang Lida , Cheng Yuan , Huang Kai , Zhou Yu , Ma Yanqun , Zhang Mengci 
Published: May 2018

AbstractFatty liver disease is a growing problem in fish aquaculture and there is an urgent need to identify causes and possible remedies. In the present study, the effects of treating fatty liver disease in the Nile tilapia (Oreochromis niloticus Linnaeus, 1758) with an extract derived from a herb, Sedum sarmentosum Bunge (SSB), was investigated. We found that the SSB extract could restore the changes to feed coefficient, immune capacity, and pathological index caused by fatty liver disease, and also prevent apoptosis in hepatocytes. An RNA-seq analysis showed that treatment with SSB extract altered expression of genes in the lipid metabolic process, metabolic process, and oxidation-reduction process. Our results suggest that disorders of the PPAR and p53 signaling pathways may be involved in steatohepatitis development and in the therapeutic mechanism of the SSB extract treatment; these observations shed new light on possible treatment of steatohepatitis.
Phenotypic plasticity in a population of odonates
Authors: Bowman Randi M. , Schmidt Sharol , Weeks Chelsea , Clark Hunter , Brown Christopher , Latta Leigh C. , Edgehouse Michael 
Published: May 2018

AbstractThe maintenance of phenotypic plasticity within a species ensures survival through environmental flux. Plastic strategies are increasingly important given the number and magnitude of modern anthropogenic threats to the environment. We tested for phenotypic plasticity in the odonate Argia vivida in response to resource limitation. By limiting food availability, effectively inducing hunger, we were able to quantify shifts in agonistic behavior during intraspecific interactions. Scoring behavior in one-on-one combat trials after 1 and 4 days without food revealed phenotypic plasticity. Three classes of genotypes were identified, genotypes exhibiting either increased aggression, decreased aggression, or no phenotypic plasticity, in response to resource limitation. The variable plastic strategies in this population of odonates likely aids in maintaining fitness in fluctuating environments.
HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal
Authors: Rossi Lucia , Battistelli Cecilia , de Turris Valeria , Noce Valeria , Zwergel Clemens , Valente Sergio , Moioli Alessandra , Manzione Andrea , Palladino Marco , Bordoni Veronica , Domenici Alessandro , Menè Paolo , Mai Antonello , Tripodi Marco , Strippoli Raffaele 
Published: May 2018

AbstractPeritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in a variety of conditions including peritoneal dialysis (PD), post-surgery adhesions and peritoneal metastases. The acquisition of invasive and pro-fibrotic abilities by mesothelial cells (MCs) through induction of MMT, a cell-specific form of EMT, plays a main role in this process. Aim of this study was to evaluate possible effects of histone deacetylase (HDAC) inhibitors, key components of the epigenetic machinery, in counteracting MMT observed in MCs isolated from effluent of PD patients. HDAC inhibitors with different class/isoform selectivity have been used for pharmacological inhibition. While the effect of other inhibitors was limited to a partial E-cadherin re-expression, MS-275, a HDAC1-3 inhibitor, promoted: (i) downregulation of mesenchymal markers (MMP2, Col1A1, PAI-1, TGFβ1, TGFβRI) (ii) upregulation of epithelial markers (E-cadherin, Occludin), (iii) reacquisition of an epithelial-like morphology and (iv) marked reduction of cellular invasiveness. Results were confirmed by HDAC1 genetic silencing. Mechanistically, MS-275 causes: (i) increase of nuclear histone H3 acetylation (ii) rescue of the acetylation profile on E-cadherin promoter, (iii) Snail functional impairment. Overall, our study, pinpointing a role for HDAC1, revealed a new player in the regulation of peritoneal fibrosis, providing the rationale for future therapeutic opportunities.
Experimental verification of high energy laser-generated impulse for remote laser control of space debris
Authors: Lorbeer Raoul-Amadeus , Zwilich Michael , Zabic Miroslav , Scharring Stefan , Eisert Lukas , Wilken Jascha , Schumacher Dennis , Roth Markus , Eckel Hans-Albert 
Published: May 2018

AbstractWalking along a beach one may notice debris being washed ashore from the vast oceans. Then, turning your head up at night you even might noticed a shooting star or a bright spot passing by. Chances are, that you witnessed space debris, endangering future space flight in lower earth orbit. If it was possible to turn cm-sized debris into shooting stars the problem might be averted. Unfortunately, these fragments counting in the 100 thousands are not controllable. To possibly regain control we demonstrate how to exert forces on a free falling debris object from a distance by ablating material with a high energy ns-laser-system. Thrust effects did scale as expected from simulations and led to speed gains above 0.3 m/s per laser pulse in an evacuated micro-gravity environment.