bluuebunny/crossref_metadata_2025_split huggingface dataset:
Li Partitioning Into Coccoliths of Emiliania huxleyi: Evaluating the General Role of “Vital Effects” in Explaining Element Partitioning in Biogenic Carbonates
Authors: Langer Gerald , Sadekov Aleksey , Greaves Mervyn , Nehrke Gernot , Probert Ian , Misra Sambuddha , Thoms Silke 
Published: June 2020

AbstractEmiliania huxleyi cells were grown in artificial seawater of different Li and Ca concentrations and coccolith Li/Ca ratios determined. Coccolith Li/Ca ratios were positively correlated to seawater Li/Ca ratios only if the seawater Li concentration was changed, not if the seawater Ca concentration was changed. This Li partitioning pattern of E. huxleyi was previously also observed in the benthic foraminifer Amphistegina lessonii and inorganically precipitated calcite. We argue that Li partitioning in both E. huxleyi and A. lessonii is dominated by a coupled transmembrane transport of Li and Ca from seawater to the site of calcification. We present a refined version of a recently proposed transmembrane transport model for Li and Ca. The model assumes that Li and Ca enter the cell via Ca channels, the Li flux being dependent on the Ca flux. While the original model features a linear function to describe the experimental data, our refined version uses a power function, changing the stoichiometry of Li and Ca. The version presented here accurately predicts the observed dependence of DLi on seawater Li/Ca ratios. Our data demonstrate that minor element partitioning in calcifying organisms is partly mediated by biological processes even if the partitioning behavior of the calcifying organism is indistinguishable from that of inorganically precipitated calcium carbonate.
Characteristics of Minor Ions and Electrons in Flux Transfer Events Observed by the Magnetospheric Multiscale Mission
Authors: Petrinec S. M. , Burch J. L. , Chandler M. , Farrugia C. J. , Fuselier S. A. , Giles B. L. , Gomez R. G. , Mukherjee J. , Paterson W. R. , Russell C. T. , Sibeck D. G. , Strangeway R. J. , Torbert R. B. , Trattner K. J. , Vines S. K. , Zhao C. 
Published: June 2020

AbstractIn this study, the ion composition of flux transfer events (FTEs) observed within the magnetosheath proper is examined. These FTEs were observed just upstream of the Earth's postnoon magnetopause by the National Aeronautics and Space Administration (NASA) Magnetospheric Multiscale (MMS) spacecraft constellation. The minor ion characteristics are described using energy spectrograms, flux distributions, and ion moments as the constellation encountered each FTE. In conjunction with electron data and magnetic field observations, such observations provide important contextual information on the formation, topologies, and evolution of FTEs. In particular, minor ions, when combined with the field‐aligned streaming of electrons, are reliable indicators of FTE topology. The observations are also placed (i) in context of the solar wind magnetic field configuration, (ii) the connection of the sampled flux tube to the ionosphere, and (iii) the location relative to the modeled reconnection line at the magnetopause. While protons and alpha particles were often depleted within the FTEs relative to the surrounding magnetosheath plasma, the He+ and O+ populations showed clear enhancements either near the center or near the edges of the FTE, and the bulk plasma flow directions are consistent with magnetic reconnection northward of the spacecraft and convection from the dayside toward the flank magnetopause.
Independent influences of maternal obesity and fetal sex on maternal cardiovascular adaptation to pregnancy: a prospective cohort study
Authors: Teulings Noor E. W. D. , Wood Angela M. , Sovio Ulla , Ozanne Susan E. , Smith Gordon C. S. , Aiken Catherine E. 
Published: June 2020

Abstract
Background/Objectives
Successful pregnancy requires the de novo creation of low-resistance utero-placental and feto-placental circulations and incomplete remodeling of this vasculature can lead to maternal or fetal compromise. Maternal BMI and fetal sex are known to influence vascular compliance and placental development, but it is unknown if these are independent or synergistic effects. Here we aim to investigate the impact of maternal obesity, fetal sex, and any interaction thereof on maternal cardiovascular adaptation to pregnancy, by assessing the physiological drop of uterine artery doppler pulsatility (UtA-PI) and umbilical artery doppler pulsatility index (UA-PI) over gestation.

Subjects/Methods
Nulliparous women with a singleton pregnancy participating in a prospective cohort study (n = 4212) underwent serial UtA-PI and UA-PI measurements at 20-, 28- and 36-weeks gestation. Linear mixed regression models were employed to investigate the influence of maternal BMI, fetal sex and interactions thereof on the magnitude of change in UtA-PI and UA-PI.

Results
Throughout gestation, UtA-PI was higher for male fetuses and UA-PI was higher for female fetuses. The physiological drop of UtA-PI was significantly smaller in overweight (change −24.3% [95%CI −22.3, −26.2]) and obese women (change −21.3% [−18.3, −24.3]), compared to normal-weight women (change −25.7% [−24.3, −27.0]) but did not differ by fetal sex. The physiological drop in UA-PI was greater for female than male fetuses (–32.5% [−31.5, −33.5] vs. −30.7% [−29.8, −31.7]) but did not differ by maternal BMI. No interactions between maternal BMI and fetal sex were found.

Conclusions
Maternal cardiovascular adaptation to pregnancy is independently associated with maternal BMI and fetal sex. Our results imply sexual dimorphism in both maternal cardiovascular adaptation and feto-placental resistance.
Metformin effectively treats Tsc1 deletion-caused kidney pathology by upregulating AMPK phosphorylation
Authors: Fang Yili , Li Fang , Qi Chenyang , Mao Xing , Wang Feng , Zhao Zhonghua , Chen Jian-Kang , Zhang Zhigang , Wu Huijuan 
Published: June 2020

AbstractTuberous sclerosis complex (TSC) is characterized by hamartomatous lesions in multiple organs, with most patients developing polycystic kidney disease and leading to a decline of renal function. TSC is caused by loss-of-function mutations in either Tsc1 or Tsc2 gene, but currently, there is no effective treatment for aberrant kidney growth in TSC patients. By generating a renal proximal tubule-specific Tsc1 gene-knockout (Tsc1ptKO) mouse model, we observed that Tsc1ptKO mice developed aberrantly enlarged kidneys primarily due to hypertrophy and proliferation of proximal tubule cells, along with some cystogenesis, interstitial inflammation, and fibrosis. Mechanistic studies revealed inhibition of AMP-activated protein kinase (AMPK) phosphorylation at Thr-172 and activation of Akt phosphorylation at Ser-473 and Thr-308. We therefore treated Tsc1ptKO mice with the AMPK activator, metformin, by daily intraperitoneal injection. Our results indicated that metformin increased the AMPK phosphorylation, but decreased the Akt phosphorylation. These signaling modulations resulted in inhibition of proliferation and induction of apoptosis in the renal proximal tubule cells of Tsc1ptKO mice. Importantly, metformin treatment effectively prevented aberrant kidney enlargement and cyst growth, inhibited inflammatory response, attenuated interstitial fibrosis, and protected renal function. The effects of metformin were further confirmed by in vitro experiments. In conclusion, this study indicates a potential therapeutic effect of metformin on Tsc1 deletion-induced kidney pathology, although currently metformin is primarily prescribed to treat patients with type 2 diabetes.
Structure and mechanism of DNA delivery of a gene transfer agent
Authors: Bárdy Pavol , Füzik Tibor , Hrebík Dominik , Pantůček Roman , Thomas Beatty J. , Plevka Pavel 
Published: June 2020

AbstractAlphaproteobacteria, which are the most abundant microorganisms of temperate oceans, produce phage-like particles called gene transfer agents (GTAs) that mediate lateral gene exchange. However, the mechanism by which GTAs deliver DNA into cells is unknown. Here we present the structure of the GTA of Rhodobacter capsulatus (RcGTA) and describe the conformational changes required for its DNA ejection. The structure of RcGTA resembles that of a tailed phage, but it has an oblate head shortened in the direction of the tail axis, which limits its packaging capacity to less than 4,500 base pairs of linear double-stranded DNA. The tail channel of RcGTA contains a trimer of proteins that possess features of both tape measure proteins of long-tailed phages from the family Siphoviridae and tail needle proteins of short-tailed phages from the family Podoviridae. The opening of a constriction within the RcGTA baseplate enables the ejection of DNA into bacterial periplasm.
DG–CA3 circuitry mediates hippocampal representations of latent information
Authors: Keinath Alexandra T. , Nieto-Posadas Andrés , Robinson Jennifer C. , Brandon Mark P. 
Published: June 2020

AbstractSurvival in complex environments necessitates a flexible navigation system that incorporates memory of recent behavior and associations. Yet, how the hippocampal spatial circuit represents latent information independent of sensory inputs and future goals has not been determined. To address this, we image the activity of large ensembles in subregion CA1 via wide-field fluorescent microscopy during a novel behavioral paradigm. Our results demonstrate that latent information is represented through reliable firing rate changes during unconstrained navigation. We then hypothesize that the representation of latent information in CA1 is mediated by pattern separation/completion processes instantiated upstream within the dentate gyrus (DG) and CA3 subregions. Indeed, CA3 ensemble recordings reveal an analogous code for latent information. Moreover, selective chemogenetic inactivation of DG–CA3 circuitry completely and reversibly abolishes the CA1 representation of latent information. These results reveal a causal and specific role of DG–CA3 circuitry in the maintenance of latent information within the hippocampus.
Dual Role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma
Authors: Tao Weiwei , Chu Chengwei , Zhou Wenchao , Huang Zhi , Zhai Kui , Fang Xiaoguang , Huang Qian , Zhang Aili , Wang Xiuxing , Yu Xingjiang , Huang Haidong , Wu Qiulian , Sloan Andrew E. , Yu Jennifer S. , Li Xiaoxia , Stark George R. , Rich Jeremy N. , Bao Shideng 
Published: June 2020

AbstractThe interplay between glioma stem cells (GSCs) and the tumor microenvironment plays crucial roles in promoting malignant growth of glioblastoma (GBM), the most lethal brain tumor. However, the molecular mechanisms underlying this crosstalk are incompletely understood. Here, we show that GSCs secrete the Wnt‐induced signaling protein 1 (WISP1) to facilitate a pro-tumor microenvironment by promoting the survival of both GSCs and tumor-associated macrophages (TAMs). WISP1 is preferentially expressed and secreted by GSCs. Silencing WISP1 markedly disrupts GSC maintenance, reduces tumor-supportive TAMs (M2), and potently inhibits GBM growth. WISP1 signals through Integrin α6β1-Akt to maintain GSCs by an autocrine mechanism and M2 TAMs through a paracrine manner. Importantly, inhibition of Wnt/β-catenin-WISP1 signaling by carnosic acid (CA) suppresses GBM tumor growth. Collectively, these data demonstrate that WISP1 plays critical roles in maintaining GSCs and tumor-supportive TAMs in GBM, indicating that targeting Wnt/β-catenin-WISP1 signaling may effectively improve GBM treatment and the patient survival.
ORIGIN: a novel and compact Laser Desorption – Mass Spectrometry system for sensitive in situ detection of amino acids on extraterrestrial surfaces
Authors: Ligterink Niels F. W. , Grimaudo Valentine , Moreno-García Pavel , Lukmanov Rustam , Tulej Marek , Leya Ingo , Lindner Robert , Wurz Peter , Cockell Charles S. , Ehrenfreund Pascale , Riedo Andreas 
Published: June 2020

AbstractFor the last four decades space exploration missions have searched for molecular life on planetary surfaces beyond Earth. Often pyrolysis gas chromatography mass spectrometry has been used as payload on such space exploration missions. These instruments have relatively low detection sensitivity and their measurements are often undermined by the presence of chloride salts and minerals. Currently, ocean worlds in the outer Solar System, such as the icy moons Europa and Enceladus, represent potentially habitable environments and are therefore prime targets for the search for biosignatures. For future space exploration missions, novel measurement concepts, capable of detecting low concentrations of biomolecules with significantly improved sensitivity and specificity are required. Here we report on a novel analytical technique for the detection of extremely low concentrations of amino acids using ORIGIN, a compact and lightweight laser desorption ionization – mass spectrometer designed and developed for in situ space exploration missions. The identified unique mass fragmentation patterns of amino acids coupled to a multi-position laser scan, allows for a robust identification and quantification of amino acids. With a detection limit of a few fmol mm−2, and the possibility for sub-fmol detection sensitivity, this measurement technique excels current space exploration systems by three orders of magnitude. Moreover, our detection method is not affected by chemical alterations through surface minerals and/or salts, such as NaCl that is expected to be present at the percent level on ocean worlds. Our results demonstrate that ORIGIN is a promising instrument for the detection of signatures of life and ready for upcoming space missions, such as the Europa Lander.
Hyperpolarized [1,4-13C]fumarate imaging detects microvascular complications and hypoxia mediated cell death in diabetic nephropathy
Authors: Laustsen Christoffer , Nielsen Per Mose , Qi Haiyun , Løbner Mette Hadberg , Palmfeldt Johan , Bertelsen Lotte Bonde 
Published: June 2020

AbstractToday, there is a general lack of prognostic biomarkers for development of renal disease and in particular diabetic nephropathy. Increased glycolytic activity, lactate accumulation and altered mitochondrial oxygen utilization are hallmarks of diabetic kidney disease. Fumarate hydratase activity has been linked to mitochondrial dysfunction as well as activation of the hypoxia inducible factor, induction of apoptosis and necrosis. Here, we investigate fumarate hydratase activity in biofluids in combination with the molecular imaging probe, hyperpolarized [1,4-13C2]fumarate, to identify the early changes associated with hemodynamics and cell death in a streptozotocin rat model of type 1 diabetes. We found a significantly altered hemodynamic signature of [1,4-13C2]fumarate in the diabetic kidneys as well as an systemic increased metabolic conversion of fumarate-to-malate, indicative of increased cell death associated with progression of diabetes, while little to no renal specific conversion was observed. This suggest apoptosis as the main cause of cell death in the diabetic kidney. This is likely resulting from an increased reactive oxygen species production following uncoupling of the electron transport chain at complex II. The mechanism coupling the enzyme leakage and apoptotic phenotype is hypoxia inducible factor independent and seemingly functions as a protective mechanism in the kidney cells.
Using Accelerated Molecular Dynamics Simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein
Authors: Valente Renan Patrick da Penha , Souza Rafael Conceição de , de Medeiros Muniz Gabriela , Ferreira João Elias Vidueira , de Miranda Ricardo Morais , e Lima Anderson Henrique Lima , Vianez Junior João Lídio da Silva Gonçalves 
Published: June 2020

AbstractThe envelope (E) protein is an important target for antibodies in flavivirus. Literature reports that the mutation T198F, located at the domain I-II hinge of the E protein, regulates viral breathing and increases the accessibility of a distal cryptic epitope located on the fusion loop, having a direct impact in the neutralization of West Nile virus (WNV). Our study aimed to describe, using accelerated molecular dynamics simulations, the effects of the T198F mutation in the flexibility of the E protein of WNV and to elucidate the mechanism that regulates epitope accessibility. The simulation results revealed that the mutation favors the formation of alternative hydrogen bonds, hampering the bending movement between domains I and II. We hypothesized that this is the mechanism by which the T198F mutation, located at the middle of the protein, locks the distal cryptc epitope near a single preferred conformation, rendering it more prone to recognition by antibodies.
Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation
Authors: Barthez Marine , Poplineau Mathilde , Elrefaey Marwa , Caruso Nathalie , Graba Yacine , Saurin Andrew J. 
Published: June 2020

AbstractAutophagy is an essential cellular process that maintains homeostasis by recycling damaged organelles and nutrients during development and cellular stress. ZKSCAN3 is the sole identified master transcriptional repressor of autophagy in human cell lines. How ZKSCAN3 achieves autophagy repression at the mechanistic or organismal level however still remains to be elucidated. Furthermore, Zkscan3 knockout mice display no discernable autophagy-related phenotypes, suggesting that there may be substantial differences in the regulation of autophagy between normal tissues and tumor cell lines. Here, we demonstrate that vertebrate ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy repression. Expression of ZKSCAN3 in Drosophila prevents premature autophagy onset due to loss of M1BP function and conversely, M1BP expression in human cells can prevent starvation-induced autophagy due to loss of nuclear ZKSCAN3 function. In Drosophila ZKSCAN3 binds genome-wide to sequences targeted by M1BP and transcriptionally regulates the majority of M1BP-controlled genes, demonstrating the evolutionary conservation of the transcriptional repression of autophagy. This study thus allows the potential for transitioning the mechanisms, gene targets and plethora metabolic processes controlled by M1BP onto ZKSCAN3 and opens up Drosophila as a tool in studying the function of ZKSCAN3 in autophagy and tumourigenesis.
Impediometric Electrochemical Sensor Based on The Inspiration of Carnation Italian Ringspot Virus Structure to Detect an Attommolar of miR
Authors: Ghazizadeh E. , Moosavifard Seyyed Ebrahim , Daneshmand Negin , Kaverlavani Saeid kamari 
Published: June 2020

AbstractElectrochemical sensors are the tools to detect the accurate and sensitive miRs. There is the challenge to increase the power and sensitivity of the surface for the electrochemical sensor. We design a virus-like hallow structure of cuco2o4 that it holds the large amounts of p19 protein by mimicking of inherent virus (Carnation italian ringspot virus) to detect 21mir with the limit of detection (LOD = 1aM). The electrochemical measurements are performed between the potentials at −0.3 V and +0.3 V with 1 mM [Fe(CN)6] −3/−4. After dropping the cuco2o4 on the SCPE (screen carbon printed electrode), the sensor is turned on due to the high electrochemical properties. Then, p19 proteins move into the hallow structure and inhibit the exchange of electrochemical reactions between the shells and the sensor is turned off. Then, adding the duplexes of RNA/miRs cause to increase the electrochemical property of p19 due to the change of p19 conformation and the system is turned on, again. So, for the first time, a virus-like hallow structure has been used to detect the 21miR in the human serum, MCF-7, Hella cells, with high sensitivity, specificity, and reproducibility in few minutes.
Discordance for genotypic sex in phenotypic female Atlantic salmon (Salmo salar) is related to a reduced sdY copy number
Authors: Brown Morgan S. , Evans Brad S. , Afonso Luis O. B. 
Published: June 2020

AbstractThe master sex determinant in rainbow trout (Oncorhynchus mykiss), sexually dimorphic on the Y chromosome (sdY), is strongly but not perfectly associated with male phenotype in several other species from the family Salmonidae. Currently, the cause and implications of discordance forsdY-predicted genotypic sex and phenotypic sex in these species is unclear. Using an established multiplex PCR test for exons 2 and 3 ofsdY, we demonstrated thatsdY-predicted genotypic sex was discordant with histologically evidenced phenotypic sex in 4% of 176 Tasmanian Atlantic salmon. All discordant individuals were phenotypic females presenting a male genotype. Using real-time qPCR assays that we developed and validated for exons 2, 3 and 4 ofsdY, all genotype-phenotype discordant females were confirmed to possesssdY, albeit at a reduced number of copies when compared to phenotypic males. The real-time qPCR assays also demonstrated reduced levels ofsdYin 30% of phenotypic females that the established multiplex PCR-based test indicated to be devoid ofsdY. These findings suggestsdYmay be reduced in copy number or mosaicked in the genomic DNA ofsdY-positive phenotypic female Atlantic salmon and highlight the importance of understanding the effects of reducedsdYcopies on the development of phenotypic sex.
Dynamic K-edge Subtraction Fluoroscopy at a Compact Inverse-Compton Synchrotron X-ray Source
Authors: Kulpe Stephanie , Dierolf Martin , Günther Benedikt , Brantl Johannes , Busse Madleen , Achterhold Klaus , Gleich Bernhard , Pfeiffer Franz , Pfeiffer Daniela 
Published: June 2020

AbstractX-ray fluoroscopy is a commonly applied diagnostic tool for morphological and functional evaluation of the intestine in clinical routine. Acquisition of repetitive X-ray images following oral or rectal application of iodine contrast agent visualizes the time dependent distribution of the contrast medium, and helps to detect for example leakages, tumors or functional disorders. However, movements of the intestine and air trapped inside usually prevent temporal subtraction imaging to be applied to fluoroscopy of the gastrointestinal tract. K-edge subtraction (KES) imaging would enable subtraction fluoroscopy because it allows for imaging of moving organs with little artefacts. Although KES imaging is a well established technique at synchrotron sources, this imaging method is not applied in clinical routine as it relies on brilliant synchrotron radiation. Recently emerging compact synchrotron X-ray sources could provide a quasi-monochromatic, high-flux X-ray beam and allow for the application of KES in a laboratory environment. Here, we present a filter-based dynamic KES approach at the Munich Compact Light Source (MuCLS), the first user-dedicated installation of a compact synchrotron X-ray source worldwide. Compared to conventional temporal subtraction X-ray radiography, our approach increases the contrast while reducing the generated image artefacts.