bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metadherin enhances vulnerability of cancer cells to ferroptosis
Authors: Bi Jianling , Yang Shujie , Li Long , Dai Qun , Borcherding Nicholas , Wagner Brett A. , Buettner Garry R. , Spitz Douglas R. , Leslie Kimberly K. , Zhang Jun , Meng Xiangbing 
Published: September 2019

AbstractFerroptosis is an iron-dependent, non-apoptotic form of regulated cell death driven by lipid hydroperoxides within biological membranes. Although therapy-resistant mesenchymal-high cancers are particularly vulnerable to ferroptosis inducers, especially phospholipid glutathione peroxidase 4 (GPx4) inhibitors, the underlying mechanism is yet to be deciphered. As such, the full application of GPx4 inhibitors in cancer therapy remains challenging. Here we demonstrate that metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc− heterodimerization partner), at both the messenger RNA and protein levels. Our metabolomic studies demonstrated that MTDH reduced intracellular cysteine, but increased glutamate levels, ultimately decreasing levels of glutathione and setting the stage for increased vulnerability to ferroptosis. Finally, we observed an enhanced antitumor effect when we combined various ferroptosis inducers both in vitro and in vivo; the level of MTDH correlated with the ferroptotic effect. We have demonstrated for the first time that MTDH enhances the vulnerability of cancer cells to ferroptosis and may serve as a therapeutic biomarker for future ferroptosis-centered cancer therapy.
C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
Authors: Zhang Liwen , Zhou Fangfang , Yu Xialian , Zhu Yufei , Zhou Ying , Liu Jian , Liu Yunzi , Ma Qingyang , Zhang Yuchao , Wang Weiming , Chen Nan 
Published: September 2019

AbstractKidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of C/EBPα in podocyte senescence and kidney aging by generating a genetically modified mouse model of chronological aging in which C/EBPα was selectively deleted in podocytes and by overexpressing C/EBPα in cultured podocytes, in which premature senescence was induced by treatment with adriamycin. Moreover, we illuminated the mechanisms by which podocyte senescence causes tubular impairment by stimulating HK-2 cells with bovine serum albumin (BSA) and chloroquine. Our findings suggest that C/EBPα knockout in podocytes aggravates podocyte senescence through the AMPK/mTOR pathway, leading to glomerulosclerosis, and that subsequent albuminuria exacerbates the epithelial–mesenchymal transdifferentiation of senescent tubular cells by suppressing autophagy. These observations highlight the importance of C/EBPα as a new potential target in kidney aging.
Stakeholders’ perspectives on the post-mortem use of genetic and health-related data for research: a systematic review
Authors: Bak Marieke A. R. , Ploem M. Corrette , Ateşyürek Hakan , Blom Marieke T. , Tan Hanno L. , Willems Dick L. 
Published: September 2019

AbstractThe majority of biobank policies and consent forms do not address post-mortem use of data for medical research, thus causing uncertainty after research participants’ death. This systematic review identifies studies examining stakeholders’ perspectives on this issue. We conducted a search in MEDLINE, CINAHL, EMBASE and Web of Science. Findings were categorised in two themes: (1) views on the use of data for medical research after participants’ death, and (2) perspectives regarding the post-mortem return of individual genetic research results. An important subtheme was the appropriate authority and degree of control over posthumous use of data. The sixteen included studies all focused on genetic data and used quantitative and qualitative methods to survey perspectives of research participants, family members, researchers and Institutional Review Board members. Acceptability of post-mortem use of data for medical research was high among research participants and their relatives. Most stakeholders thought participants should be informed about post-mortem research uses during initial consent. Between lay persons and professionals, disagreement exists about whether relatives should receive actionable genetic findings, and whether the deceased’s previous preferences can be overridden. We conclude that regulations and ethical guidance should leave room for post-mortem use of personal data for research, provided that informed consent procedures are transparent on this issue, including the return of individual research findings to relatives. Future research is needed to explore underlying causes for differences in views, as well as ethical and legal issues on the appropriate level of control by deceased research participants (while alive) and their relatives.
Non-Gaussian noise spectroscopy with a superconducting qubit sensor
Authors: Sung Youngkyu , Beaudoin Félix , Norris Leigh M. , Yan Fei , Kim David K. , Qiu Jack Y. , von Lüpke Uwe , Yoder Jonilyn L. , Orlando Terry P. , Gustavsson Simon , Viola Lorenza , Oliver William D. 
Published: September 2019

AbstractAccurate characterization of the noise influencing a quantum system of interest has far-reaching implications across quantum science, ranging from microscopic modeling of decoherence dynamics to noise-optimized quantum control. While the assumption that noise obeys Gaussian statistics is commonly employed, noise is generically non-Gaussian in nature. In particular, the Gaussian approximation breaks down whenever a qubit is strongly coupled to discrete noise sources or has a non-linear response to the environmental degrees of freedom. Thus, in order to both scrutinize the applicability of the Gaussian assumption and capture distinctive non-Gaussian signatures, a tool for characterizing non-Gaussian noise is essential. Here, we experimentally validate a quantum control protocol which, in addition to the spectrum, reconstructs the leading higher-order spectrum of engineered non-Gaussian dephasing noise using a superconducting qubit as a sensor. This first experimental demonstration of non-Gaussian noise spectroscopy represents a major step toward demonstrating a complete spectral estimation toolbox for quantum devices.
Polar and phase domain walls with conducting interfacial states in a Weyl semimetal MoTe2
Authors: Huang Fei-Ting , Joon Lim Seong , Singh Sobhit , Kim Jinwoong , Zhang Lunyong , Kim Jae-Wook , Chu Ming-Wen , Rabe Karin M. , Vanderbilt David , Cheong Sang-Wook 
Published: September 2019

AbstractMuch of the dramatic growth in research on topological materials has focused on topologically protected surface states. While the domain walls of topological materials such as Weyl semimetals with broken inversion or time-reversal symmetry can provide a hunting ground for exploring topological interfacial states, such investigations have received little attention to date. Here, utilizing in-situ cryogenic transmission electron microscopy combined with first-principles calculations, we discover intriguing domain-wall structures in MoTe2, both between polar variants of the low-temperature(T) Weyl phase, and between this and the high-T higher-order topological phase. We demonstrate how polar domain walls can be manipulated with electron beams and show that phase domain walls tend to form superlattice-like structures along the c axis. Scanning tunneling microscopy indicates a possible signature of a conducting hinge state at phase domain walls. Our results open avenues for investigating topological interfacial states and unveiling multifunctional aspects of domain walls in topological materials.
Identification of proteins and miRNAs that specifically bind an mRNA in vivo
Authors: Theil Kathrin , Imami Koshi , Rajewsky Nikolaus 
Published: September 2019

AbstractUnderstanding regulation of an mRNA requires knowledge of its regulators. However, methods for reliable de-novo identification of proteins binding to a particular RNA are scarce and were thus far only successfully applied to abundant noncoding RNAs in cell culture. Here, we present vIPR, an RNA-protein crosslink, RNA pulldown, and shotgun proteomics approach to identify proteins bound to selected mRNAs inC. elegans. Applying vIPR to the germline-specific transcriptgld-1led to enrichment of known and novel interactors. By comparing enrichment upongld-1andlin-41pulldown, we demonstrate that vIPR recovers both common and specific RNA-binding proteins, and we validate DAZ-1 as a specificgld-1regulator. Finally, combining vIPR with small RNA sequencing, we recover known and biologically important transcript-specific miRNA interactions, and we identifymiR-84as a specific interactor of thegld-1transcript. We envision that vIPR will provide a platform for investigating RNA in vivo regulation in diverse biological systems.
Membrane adsorbers with ultrahigh metal-organic framework loading for high flux separations
Authors: Wang Hang , Zhao Shuang , Liu Yi , Yao Ruxin , Wang Xiaoqi , Cao Yuhua , Ma Dou , Zou Mingchu , Cao Anyuan , Feng Xiao , Wang Bo 
Published: September 2019

AbstractMetal-organic frameworks (MOFs) with high porosity and designable functionality make it possible to access the merits of high permeability and selectivity. However, scalable fabrication methods to produce mixed matrix membranes (MMMs) with good flexibility and ultrahigh MOF loading are urgently needed yet largely unmet. Herein, we report a thermally induced phase separation-hot pressing (TIPS-HoP) strategy to roll-to-roll produce 10 distinct MOF-membranes (loadings up to 86 wt%). Ultrahigh-molecular-weight polyethylene interweaving the MOF particles contributes to their mechanical strength. Rejections (99%) of organic dyes with a water flux of 125.7 L m–2 h–1 bar–1 under cross-flow filtration mode. The micron-sized channels between the MOF particles translate into fast water permeation, while the porous MOFs reject solutes through rapid adsorption. This strategy paves ways for developing high-performance membrane adsorbers for crucial separation processes. As a proof-of-concept, the abilities of the membrane adsorbers for separating racemates and proteins have been demonstrated.
Surface acoustic wave photonic devices in silicon on insulator
Authors: Munk Dvir , Katzman Moshe , Hen Mirit , Priel Maayan , Feldberg Moshe , Sharabani Tali , Levy Shahar , Bergman Arik , Zadok Avi 
Published: September 2019

AbstractOpto-mechanical interactions in planar photonic integrated circuits draw great interest in basic research and applications. However, opto-mechanics is practically absent in the most technologically significant photonics platform: silicon on insulator. Previous demonstrations required the under-etching and suspension of silicon structures. Here we present surface acoustic wave-photonic devices in silicon on insulator, up to 8 GHz frequency. Surface waves are launched through absorption of modulated pump light in metallic gratings and thermo-elastic expansion. The surface waves are detected through photo-elastic modulation of an optical probe in standard race-track resonators. Devices do not involve piezo-electric actuation, suspension of waveguides or hybrid material integration. Wavelength conversion of incident microwave signals and acoustic true time delays up to 40 ns are demonstrated on-chip. Lastly, discrete-time microwave-photonic filters with up to six taps and 20 MHz-wide passbands are realized using acoustic delays. The concept is suitable for integrated microwave-photonics signal processing.
Sulphur isotopes of alkaline magmas unlock long-term records of crustal recycling on Earth
Authors: Hutchison William , Babiel Rainer J. , Finch Adrian A. , Marks Michael A. W. , Markl Gregor , Boyce Adrian J. , Stüeken Eva E. , Friis Henrik , Borst Anouk M. , Horsburgh Nicola J. 
Published: September 2019

AbstractEarth’s surface and mantle sulphur reservoirs are connected via subduction, crustal recycling and volcanism. Although oceanic hotspot lavas currently provide the best constraints on the deep sulphur cycle, their restricted age range (<200 Ma) means they cannot reveal temporal variations in crustal recycling over Earth history. Sulphur-rich alkaline magmas offer the solution because they are associated with recycled sources (i.e. metasomatized lithospheric mantle and plumes) and, crucially, are found throughout the geological record. Here, we present a detailed study of sulphur isotope fractionation in a Mesoproterozoic alkaline province in Greenland and demonstrate that an enriched subduction-influenced source (δ34S of +1 to +5‰) can be reconstructed. A global δ34S compilation reveals secular variation in alkaline magma sources which support changes in the composition of the lithospheric mantle and/or Ga timescales for deep crustal recycling. Thus, alkaline magmas represent a powerful yet underutilized repository for interrogating crustal recycling through geological time.
Derailing the aspartate pathway of Mycobacterium tuberculosis to eradicate persistent infection
Authors: Hasenoehrl Erik J. , Rae Sajorda Dannah , Berney-Meyer Linda , Johnson Samantha , Tufariello JoAnn M. , Fuhrer Tobias , Cook Gregory M. , Jacobs William R. , Berney Michael 
Published: September 2019

AbstractA major constraint for developing new anti-tuberculosis drugs is the limited number of validated targets that allow eradication of persistent infections. Here, we uncover a vulnerable component of Mycobacterium tuberculosis (Mtb) persistence metabolism, the aspartate pathway. Rapid death of threonine and homoserine auxotrophs points to a distinct susceptibility of Mtb to inhibition of this pathway. Combinatorial metabolomic and transcriptomic analysis reveals that inability to produce threonine leads to deregulation of aspartate kinase, causing flux imbalance and lysine and DAP accumulation. Mtb’s adaptive response to this metabolic stress involves a relief valve-like mechanism combining lysine export and catabolism via aminoadipate. We present evidence that inhibition of the aspartate pathway at different branch-point enzymes leads to clearance of chronic infections. Together these findings demonstrate that the aspartate pathway in Mtb relies on a combination of metabolic control mechanisms, is required for persistence, and represents a target space for anti-tuberculosis drug development.
Repurposing DNA-binding agents as H-bonded organic semiconductors
Authors: Zhang Fengjiao , Lemaur Vincent , Choi Wookjin , Kafle Prapti , Seki Shu , Cornil Jérôme , Beljonne David , Diao Ying 
Published: September 2019

AbstractOrganic semiconductors are usually polycyclic aromatic hydrocarbons and their analogs containing heteroatom substitution. Bioinspired materials chemistry of organic electronics promises new charge transport mechanism and specific molecular recognition with biomolecules. We discover organic semiconductors from deoxyribonucleic acid topoisomerase inhibitors, featuring conjugated backbone decorated with hydrogen-bonding moieties distinct from common organic semiconductors. Using ellipticine as a model compound, we find that hydrogen bonds not only guide polymorph assembly, but are also critical to forming efficient charge transport pathways along π−conjugated planes when at a low dihedral angle by shortening the end-to-end distance of adjacent π planes. In the π−π stacking and hydrogen-bonding directions, the intrinsic, short-range hole mobilities reach as high as 6.5 cm2V−1s−1 and 4.2 cm2V−1s−1 measured by microwave conductivity, and the long-range apparent hole mobilities are up to 1.3 × 10–3 cm2V−1s−1 and 0.4 × 10–3 cm2V−1s−1 measured in field-effect transistors. We further demonstrate printed transistor devices and chemical sensors as potential applications.
The RNA-mediated estrogen receptor α interactome of hormone-dependent human breast cancer cell nuclei
Authors: Nassa Giovanni , Giurato Giorgio , Salvati Annamaria , Gigantino Valerio , Pecoraro Giovanni , Lamberti Jessica , Rizzo Francesca , Nyman Tuula A. , Tarallo Roberta , Weisz Alessandro 
Published: September 2019

AbstractEstrogen Receptor alpha (ERα) is a ligand-inducible transcription factor that mediates estrogen signaling in hormone-responsive cells, where it controls key cellular functions by assembling in gene-regulatory multiprotein complexes. For this reason, interaction proteomics has been shown to represent a useful tool to investigate the molecular mechanisms underlying ERα action in target cells. RNAs have emerged as bridging molecules, involved in both assembly and activity of transcription regulatory protein complexes. By applying Tandem Affinity Purification (TAP) coupled to mass spectrometry (MS) before and after RNase digestion in vitro, we generated a dataset of nuclear ERα molecular partners whose association with the receptor involves RNAs. These data provide a useful resource to elucidate the combined role of nuclear RNAs and the proteins identified here in ERα signaling to the genome in breast cancer and other cell types.
Design, synthesis, and discovery of novel oxindoles bearing 3-heterocycles as species-specific and combinatorial agents in eradicating Staphylococcus species
Authors: Shin Jonghoon , Magar Krishna Bahadur Somai , Lee Jungwoon , Kim Kwang-sun , Lee Yong Rok 
Published: September 2019

AbstractA series of new functionalized 3-indolylindolin-2-ones, 3-(1-methylpyrrol-2-yl)indolin-2-ones, and 3-(thiophen-2-yl)indolin-2-ones were synthesized by using novel indium (III)-catalysed reaction of various 3-diazoindolin-2-ones with indoles, 1-methylpyrrole, or thiophene via one-pot procedure. The newly synthesized compounds were characterized and screened for their in vitro antibacterial activity against various Staphylococcus species, including methicillin-resistant Staphylococcus aureus. results revealed that five compounds KS15, KS16, KS17, KS19, and KS20 exhibited potent and specific antibacterial activity against Staphylococcus species albeit inactive against Gram-negative bacteria. Especially, compounds exhibited superior antibacterial potency against Staphylococcus epidermidis compared to the reference drug streptomycin. The most potential compound KS16 also increased the susceptibility of Staphylococcus aureus to ciprofloxacin, gentamicin, kanamycin, and streptomycin. Among them, KS16 was found to be a synergistic compound with gentamicin and kanamycin. Furthermore, the cellular level of autolysin protein was increased from the KS16-treated Staphylococcus aureus cells. Finally, in vitro CCK-8 assays showed that KS16 exhibited no cytotoxicity at the minimum inhibitory concentrations used for killing Staphylococcus species. From all our results, novel oxindole compounds directly have lethal action or boost existing antibiotic power with the reduction of doses and toxicity in the treatment of multidrug-resistant Staphylococcus species.
Levosimendan pretreatment improves survival of septic rats after partial hepatectomy and suppresses iNOS induction in cytokine-stimulated hepatocytes
Authors: Sakaguchi Tatsuma , Hashimoto Yuki , Matsushima Hideyuki , Hishikawa Hidehiko , Nishizawa Mikio , Okumura Tadayoshi , Kaibori Masaki 
Published: September 2019

AbstractWe evaluated the survival effects and biochemical profiles of levosimendan in septic rats after partial hepatectomy and investigated its effects in cultured hepatocytes. Thirty-two rats underwent 70% hepatectomy and were randomised equally into four groups, followed by lipopolysaccharide (LPS) injection (250 µg/kg, i.v.) after 48 h. Levosimendan was given (i.p.) 1 h before LPS injection [group (A) levosimendan 2 mg/kg; (B) 1; (C) 0.5; (D) vehicle]. Survival at 7 days was increased significantly in group A compared with that in group D [A: 63%; B: 38%; C: 13%; D: 0%]. In serum, levosimendan decreased the level of tumour necrosis factor-α, interleukin (IL)-1β, IL-6 and nitric oxide (NO). In remnant livers, levosimendan inhibited inducible nitric oxide synthase (iNOS) gene expression. In primary cultured rat hepatocytes stimulated by IL-1β, levosimendan suppressed NO production by inhibiting iNOS promoter activity and stability of its mRNA.
Cigarette smoke preparations, not moist snuff, impair expression of genes involved in immune signaling and cytolytic functions
Authors: Liu Gang , Arimilli Subhashini , Savage Evan , Prasad G. L. 
Published: September 2019

AbstractCigarette smoke-induced chronic inflammation is associated with compromised immune responses. To understand how tobacco products impact immune responses, we assessed transcriptomic profiles in peripheral blood mononuclear cells (PBMCs) pretreated with Whole Smoke-Conditioned Medium (WS-CM) or Smokeless Tobacco Extracts (STE), and stimulated with lipopolysaccharide, phorbol myristate and ionomycin (agonists). Gene expression profiles from PBMCs treated with low equi-nicotine units (0.3 μg/mL) of WS-CM and one high dose of STE (100 μg/mL) were similar to those from untreated controls. Cells treated with medium and high doses of WS-CM (1.0 and 3.0 μg/mL) exhibited significantly different gene expression profiles compared to the low WS-CM dose and STE. Pre-treatment with higher doses of WS-CM inhibited the expression of several pro-inflammatory genes (IFNγ, TNFα, and IL-2), while CSF1-R and IL17RA were upregulated. Pre-treatment with high doses of WS-CM abolished agonist-stimulated secretion of IFNγ, TNF and IL-2 proteins. Pathway analyses revealed that higher doses of WS-CM inhibited NF-ĸB signaling, immune cell differentiation and inflammatory responses, and increased apoptotic pathways. Our results show that pre-treatment of PBMCs with higher doses of WS-CM inhibits immune activation and effector cytokine expression and secretion, resulting in a reduced immune response, whereas STE exerted minimal effects.
Differential Impacts of Yeasts on Feeding Behavior and Development in Larval Drosophila suzukii (Diptera:Drosophilidae)
Authors: Lewis Margaret T. , Hamby Kelly A. 
Published: September 2019

AbstractLarval Drosophila encounter and feed on a diverse microbial community within fruit. In particular, free-living yeast microbes provide a source of dietary protein critical for development. However, successional changes to the fruit microbial community may alter host quality through impacts on relative protein content or yeast community composition. For many species of Drosophila, fitness benefits from yeast feeding vary between individual yeast species, indicating differences in yeast nutritional quality. To better understand these associations, we evaluated how five species of yeast impacted feeding preference and development in larval Drosophila suzukii. Larvae exhibited a strong attraction to the yeast Hanseniaspora uvarum in pairwise yeast feeding assays. However, larvae also performed most poorly on diets containing H. uvarum, a mismatch in preference and performance that suggests differences in yeast nutritional quality are not the primary factor driving larval feeding behavior. Together, these results demonstrate that yeast plays a critical role in D. suzukii’s ecology and that larvae may have developed specific yeast associations. Further inquiry, including systematic comparisons of Drosophila larval yeast associations more broadly, will be necessary to understand patterns of microbial resource use in larvae of D. suzukii and other frugivorous species.