bluuebunny/crossref_metadata_2025_split huggingface dataset:
ULF Wave‐Associated Density Irregularities and Scintillation at the Equator
Authors: Yizengaw E. , Zesta E. , Moldwin M. B. , Magoun M. , Tripathi N. K. , Surussavadee C. , Bamba Z. 
Published: May 2018

AbstractThis paper presents independent multi‐instrument observations that address the physical mechanisms of how ultralow‐frequency (ULF) wave‐associated electric fields initiate ionospheric density fluctuation and scintillation at the equator. Since the magnetic field at the equator is entirely embedded in a relatively high‐collision and high‐conductivity medium, the condition may not be possible for the geomagnetic field to fluctuate due to ULF wave activity. This implies that the fluctuating electric field at the equator may not be produced through equatorial dynamo action due to fluctuating magnetic fields. Instead, the electric field penetrates from high latitudes and produces fluctuating magnetic field as well as modulates the vertical drift and hence causes the density to fluctuate at the equatorial region. We demonstrate this by estimating the ULF associated fluctuating electric field at high latitudes and at the equatorial region by applying the appropriate attenuation factor as it penetrates to lower latitudes. The periodicity of both electric field and density fluctuations appears to be between 6 and 9 min, which is a typical period of ULF waves in the Pc5 range. Because of its large amplitude and long periods compared to other ULF wave frequency bands, the Pc5 wave‐associated electric field, which can even be estimated using magnetograms with low sensitivity and low sampling rate (e.g., 1 min), can easily penetrate to the lower latitude region and produce significant ionospheric density fluctuations that can be strong enough to create scintillation at the equatorial region.
Application of a Luminescence‐Based Sediment Transport Model
Authors: Gray Harrison J. , Tucker Gregory E. , Mahan Shannon A. 
Published: May 2018

AbstractQuantifying the transport history of sand is a challenging but important goal in geomorphology. In this paper, we take a simple idea that luminescence is bleached during transport and regenerates during storage, and use this as a basis to re‐envision luminescence as a sediment tracer. We apply a mathematical model describing luminescence through an idealized channel and reservoir system and then compare this idealized model to real rivers to see if luminescence can reproduce known sediment transport data. We provide results from application of this luminescence method in three rivers from the mid‐Atlantic region of the United States. This method appears promising. However, as a river system diverges from idealized conditions of the mathematical model, the luminescence data diverge from model predictions. We suggest that spatial variation in the delivery of sediment from hillslopes can be reflected in the channel sediment luminescence and that luminescence acts as a function of landscape dynamics.
Midlatitude Ionospheric Irregularity Spectral Density as Determined by Ground‐Based GPS Receiver Networks
Authors: Lay Erin H. , Parker Peter A. , Light Max , Carrano Charles S. , Debchoudhury Shantanab , Haaser Robert A. 
Published: May 2018

AbstractWe present a new technique to experimentally measure the spatial spectrum of ionospheric disturbances in the spatial scale regime of 40–200 km. This technique produces a two‐dimensional (2‐D) spectrum for each time snapshot over two dense Global Positioning System (GPS) receiver networks (GPS Earth Observation Network in Japan and Plate Boundary Observatory in the Western United States). Because this technique created the spectrum from an instantaneous time snapshot, no assumptions are needed about the speed of ionospheric irregularities. We examine spectra from 3 days: one with an intense geomagnetic storm, one with significant lightning activity, and one quiet day. Radial slices along the 2‐D spectra provide one‐dimensional spectra that can be fit to a power law to quantify the steepness of the falloff in the spatial scale sizes. Continuous data of this type in a stationary location allow monitoring the variability in the 2‐D spectrum over the course of a day and comparing between days, as shown here, or even over a year or many years. We find that the spectra are highly variable over the course of a day and between the two selected regions of Japan and the Western United States. When strong traveling ionospheric disturbances (TIDs) are present, the 2‐D spectra provide information about the direction of propagation of the TIDs. We compare the TID propagation direction with horizontal wind directions from the Horizontal Wind Model. TID direction is correlated with the horizontal wind direction on all days, strongly indicating that the primary source of the TIDs measured by this technique is tropospheric.
SK channel activation is neuroprotective in conditions of enhanced ER–mitochondrial coupling
Authors: Honrath Birgit , Krabbendam Inge E. , IJsebaart Carmen , Pegoretti Valentina , Bendridi Nadia , Rieusset Jennifer , Schmidt Martina , Culmsee Carsten , Dolga Amalia M. 
Published: May 2018

AbstractAlterations in the strength and interface area of contact sites between the endoplasmic reticulum (ER) and mitochondria contribute to calcium (Ca2+) dysregulation and neuronal cell death, and have been implicated in the pathology of several neurodegenerative diseases. Weakening this physical linkage may reduce Ca2+ uptake into mitochondria, while fortifying these organelle contact sites may promote mitochondrial Ca2+ overload and cell death. Small conductance Ca2+-activated K+ (SK) channels regulate mitochondrial respiration, and their activation attenuates mitochondrial damage in paradigms of oxidative stress. In the present study, we enhanced ER–mitochondrial coupling and investigated the impact of SK channels on survival of neuronal HT22 cells in conditions of oxidative stress. Using genetically encoded linkers, we show that mitochondrial respiration and the vulnerability of neuronal cells to oxidative stress was inversely linked to the strength of ER–mitochondrial contact points and the increase in mitochondrial Ca2+ uptake. Pharmacological activation of SK channels provided protection against glutamate-induced cell death and also in conditions of increased ER–mitochondrial coupling. Together, this study revealed that SK channel activation provided persistent neuroprotection in the paradigm of glutamate-induced oxytosis even in conditions where an increase in ER–mitochondrial coupling potentiated mitochondrial Ca2+ influx and impaired mitochondrial bioenergetics.
Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment
Authors: Ruiz Lucie , Gurlo Tatyana , Ravier Magalie A. , Wojtusciszyn Anne , Mathieu Julia , Brown Matthew R. , Broca Christophe , Bertrand Gyslaine , Butler Peter C. , Matveyenko Aleksey V. , Dalle Stéphane , Costes Safia 
Published: May 2018

AbstractIn type 2 diabetes, amyloid oligomers, chronic hyperglycemia, lipotoxicity, and pro-inflammatory cytokines are detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The histone acetyl transferase p300, involved in remodeling of chromatin structure by epigenetic mechanisms, is a key ubiquitous activator of the transcriptional machinery. In this study, we report that loss of p300 acetyl transferase activity and expression leads to beta-cell apoptosis, and most importantly, that stress situations known to be associated with diabetes alter p300 levels and functional integrity. We found that proteasomal degradation is the mechanism subserving p300 loss in beta-cells exposed to hyperglycemia or pro-inflammatory cytokines. We also report that melatonin, a hormone produced in the pineal gland and known to play key roles in beta-cell health, preserves p300 levels altered by these toxic conditions. Collectively, these data imply an important role for p300 in the pathophysiology of diabetes.
Endogenous authentic OCT4A proteins directly regulate FOS/AP-1 transcription in somatic cancer cells
Authors: Zhou Yanwen , Chen Xinyu , Kang Bo , She Shiqi , Zhang Xiaobing , Chen Cheng , Li Wenxin , Chen Wenjie , Dan Songsong , Pan Xiaoyun , Liu Xiaoli , He Jianqin , Zhao Qingwei , Zhu Chenggang , Peng Ling , Wang Haoyi , Yao Hangping , Cao Hongcui , Li Lanjuan , Herlyn Meenhard , Wang Ying-Jie 
Published: May 2018

AbstractOCT4A is well established as a master transcription factor for pluripotent stem cell (PSC) self-renewal and a pioneer factor for initiating somatic cell reprogramming, yet its presence and functionality in somatic cancer cells remain controversial and obscure. By combining the CRISPR-Cas9-based gene editing with highly specific PCR assays, highly sensitive immunoassays, and mass spectrometry, we provide unequivocal evidence here that full-length authentic OCT4A transcripts and proteins were both present in somatic cancer cells, and OCT4A proteins were heterogeneously expressed in the whole cell population and when expressed, they are predominantly localized in cell nucleus. Despite their extremely low abundance (approximately three orders of magnitude lower than in PSCs), OCT4A proteins bound to the promoter/enhancer regions of the AP-1 transcription factor subunit c-FOS gene and critically regulated its transcription. Knocking out OCT4A in somatic cancer cells led to dramatic reduction of the c-FOS protein level, aberrant AP-1 signaling, dampened self-renewal capacity, deficient cell migration that were associated with cell growth retardation in vitro and in vivo, and their enhanced sensitivity to anticancer drugs. Taken together, we resolve the long-standing controversy and uncertainty in the field, and reveal a fundamental role of OCT4A protein in regulating FOS/AP-1 signaling-centered genes that mediate the adhesion, migration, and propagation of somatic cancer cells.
Inhibiting p38 MAPK alpha rescues axonal retrograde transport defects in a mouse model of ALS
Authors: Gibbs Katherine L. , Kalmar Bernadett , Rhymes Elena R. , Fellows Alexander D. , Ahmed Mahmood , Whiting Paul , Davies Ceri H. , Greensmith Linda , Schiavo Giampietro 
Published: May 2018

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the degeneration of upper and lower motor neurons. Defects in axonal transport have been observed pre-symptomatically in the SOD1G93A mouse model of ALS, and have been proposed to play a role in motor neuron degeneration as well as in other pathologies of the nervous system, such as Alzheimer’s disease and hereditary neuropathies. In this study, we screen a library of small-molecule kinase inhibitors towards the identification of pharmacological enhancers of the axonal retrograde transport of signalling endosomes, which might be used to normalise the rate of this process in diseased neurons. Inhibitors of p38 mitogen-activated protein kinases (p38 MAPK) were identified in this screen and were found to correct deficits in axonal retrograde transport of signalling endosomes in cultured primary SOD1G93A motor neurons. In vitro knockdown experiments revealed that the alpha isoform of p38 MAPK (p38 MAPKα) was the sole isoform responsible for SOD1G93A-induced transport deficits. Furthermore, we found that acute treatment with p38 MAPKα inhibitors restored the physiological rate of axonal retrograde transport in vivo in early symptomatic SOD1G93A mice. Our findings demonstrate the pathogenic effect of p38 MAPKα on axonal retrograde transport and identify a potential therapeutic strategy for ALS.
YAP-dependent ubiquitination and degradation of β-catenin mediates inhibition of Wnt signalling induced by Physalin F in colorectal cancer
Authors: Chen Chen , Zhu Dongrong , Zhang Hao , Han Chao , Xue Guimin , Zhu Tianyu , Luo Jianguang , Kong Lingyi 
Published: May 2018

AbstractAberrant activation of Wnt/β-catenin signalling is critical in the progression of human cancers, especially colorectal cancer (CRC). Therefore, inhibition of Wnt/β-catenin signalling is a significant potential target for CRC therapy. Here, we identified for the first time that Physalin F (PF), a steroid derivative isolated from Physalis angulate, acts as an antagonist of Wnt/β-catenin signalling. In vitro, PF decreased Wnt3a-induced TOPFlash reporter activity in HEK293T cells and promoted the formation of the β-catenin destruction complex. Importantly, PF also inhibited Wnt/β-catenin signalling and accelerated the degradation of β-catenin in CRC cells. However, PF did not affect the stabilization of Axin or the interaction of β-catenin with E-cadherin. Interestingly, we further found that PF promoted YAP binding to the β-catenin destruction complex, which facilitated the ubiquitination and degradation of β-catenin. Silencing and pharmacological inhibition of YAP reversed the formation of the β-catenin destruction complex induced by PF, implying that YAP binding to the β-catenin destruction complex was responsible for PF-mediated inhibition of Wnt/β-catenin signalling. Furthermore, PF observably inhibited tumour growth by down-regulating β-catenin in tumour-bearing mice. Collectively, our findings indicated that PF inhibited Wnt/β-catenin signalling by accelerating the ubiquitination and degradation of β-catenin in a YAP-dependent manner and therefore PF could be a novel potential candidate for CRC therapy.
Enhancer of zeste homolog 2-catalysed H3K27 trimethylation plays a key role in acute-on-chronic liver failure via TNF-mediated pathway
Authors: Zhou Tianhui , Sun Ye , Li Ming , Ding Yongsen , Yin Rongkun , Li Ziqiang , Xie Qing , Bao Shisan , Cai Wei 
Published: May 2018

AbstractAcute-on-chronic liver failure is mainly due to host immunity self-destruction. The histone H3 lysine 27 (H3K27) trimethylating enzyme, enhancer of zeste homolog 2 (EZH2) mediates epigenetic silencing of gene expression and regulates immunity, also involves pathogenesis of several liver diseases. The current study was to determine the role of methyltransferase EZH2 and its catalysed H3K27 trimethylation (H3K27me3) in liver failure, and to further investigate the potential target for liver failure treatment. EZH2 and its catalysed H3K27me3 were determined in peripheral blood mononuclear cells (PBMC) from liver failure patients and Kupffer cells from experimental mice. Furthermore, GSK126 (an inhibitor for EZH2 trimethylation function) was applied in liver failure mice in vivo, and lipopolysaccharide-stimulated mononuclear cells in vitro. EZH2 and H3K27me3 were significantly upregulated in human PBMC from liver failure patients or murine Kupffer cells from the liver failure animals, respectively. GSK126 ameliorated disease severity in liver failure mice, which maybe attribute to down-regulate circulating and hepatic proinflammatory cytokines, especially TNF via reducing H3K27me3. In-depth chromatin immunoprecipitation analysis unravelled that decreased enrichment of H3K27me3 on Tnf promotor, resulting in TNF elevation in Kupffer cells from liver failure mice. Nuclear factor kappa B (NF-κB) and protein kinase B (Akt) signalling pathways were activated upon lipopolysaccharide stimulation, but attenuated by using GSK126, accompanied with decreased TNF in vitro. In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-κB and Akt signalling pathways.
Epidermal glucocorticoid and mineralocorticoid receptors act cooperatively to regulate epidermal development and counteract skin inflammation
Authors: Bigas Judit , Sevilla Lisa M. , Carceller Elena , Boix Julia , Pérez Paloma 
Published: May 2018

AbstractEndogenous and synthetic glucocorticoids (GCs) regulate epidermal development and combat skin inflammatory diseases. GC actions can be mediated through the GC receptor (GR) and/or the mineralocorticoid receptor (MR), highly homologous ligand-activated transcription factors. While the role of GR as a potent anti-inflammatory mediator is well known, that of MR is not as clear, nor is whether these receptors cooperate or antagonize each other in the epidermis. To address this, we generated mice with epidermal-specific loss of both receptors (double knockout, DKO), and analyzed the phenotypical and functional consequences relative to single KOs or controls (CO). At birth, DKO epidermis displayed a phenotype of defective differentiation and inflammation, which was more severe than in either single KO, featuring neutrophil-containing infiltrates, and gene dysregulation characteristic of human psoriatic lesions. This phenotype resolved spontaneously. However, in adulthood, single or combined loss of GC receptors increased susceptibility to inflammation and hyperproliferation triggered by phorbol ester which, different to CO, was not effectively counteracted by GC treatment. Also, DKOs were more susceptible to imiquimod-induced psoriasis than CO showing severe defective epidermal differentiation and microabcesses while single KOs showed an intermediate response. Immortalized DKO keratinocytes featured increased proliferation kinetics and reduced cell size, a unique phenotype relative to single KO cells. The lack of GR and MR in keratinocytes, individual or combined, caused constitutive increases in p38 and ERK activities, which were partially reversed upon reinsertion of receptors into DKO cells. DKO keratinocytes also displayed significant increases in AP-1 and NF-κB transcriptional activities, which were partially rescued by ERK and p38 inhibition, respectively. Reinsertion of GR and MR in DKO keratinocytes resulted in physical and cooperative functional interactions that restored the transcriptional response to GCs. In conclusion, our data have revealed that epidermal GR and MR act cooperatively to regulate epidermal development and counteract skin inflammation.
Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism
Authors: Yang Ying , Hsu Phillip J. , Chen Yu-Sheng , Yang Yun-Gui 
Published: May 2018

AbstractN6-methyladenosine (m6A) is a chemical modification present in multiple RNA species, being most abundant in mRNAs. Studies on enzymes or factors that catalyze, recognize, and remove m6A have revealed its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. This review describes the current understanding of the m6A modification, particularly the functions of its writers, erasers, readers in RNA metabolism, with an emphasis on its role in regulating the isoform dosage of mRNAs.
Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation
Authors: Klammt Jürgen , Neumann David , Gevers Evelien F. , Andrew Shayne F. , Schwartz I. David , Rockstroh Denise , Colombo Roberto , Sanchez Marco A. , Vokurkova Doris , Kowalczyk Julia , Metherell Louise A. , Rosenfeld Ron G. , Pfäffle Roland , Dattani Mehul T. , Dauber Andrew , Hwa Vivian 
Published: May 2018

AbstractGrowth hormone (GH) insensitivity syndrome (GHIS) is a rare clinical condition in which production of insulin-like growth factor 1 is blunted and, consequently, postnatal growth impaired. Autosomal-recessive mutations in signal transducer and activator of transcription (STAT5B), the key signal transducer for GH, cause severe GHIS with additional characteristics of immune and, often fatal, pulmonary complications. Here we report dominant-negative, inactivating STAT5B germline mutations in patients with growth failure, eczema, and elevated IgE but without severe immune and pulmonary problems. These STAT5B missense mutants are robustly tyrosine phosphorylated upon stimulation, but are unable to nuclear localize, or fail to bind canonical STAT5B DNA response elements. Importantly, each variant retains the ability to dimerize with wild-type STAT5B, disrupting the normal transcriptional functions of wild-type STAT5B. We conclude that these STAT5B variants exert dominant-negative effects through distinct pathomechanisms, manifesting in milder clinical GHIS with general sparing of the immune system.
Uranium(III)-carbon multiple bonding supported by arene δ-bonding in mixed-valence hexauranium nanometre-scale rings
Authors: Wooles Ashley J. , Mills David P. , Tuna Floriana , McInnes Eric J. L. , Law Gareth T. W. , Fuller Adam J. , Kremer Felipe , Ridgway Mark , Lewis William , Gagliardi Laura , Vlaisavljevich Bess , Liddle Stephen T. 
Published: May 2018

AbstractDespite the fact that non-aqueous uranium chemistry is over 60 years old, most polarised-covalent uranium-element multiple bonds involve formal uranium oxidation states IV, V, and VI. The paucity of uranium(III) congeners is because, in common with metal-ligand multiple bonding generally, such linkages involve strongly donating, charge-loaded ligands that bind best to electron-poor metals and inherently promote disproportionation of uranium(III). Here, we report the synthesis of hexauranium-methanediide nanometre-scale rings. Combined experimental and computational studies suggest overall the presence of formal uranium(III) and (IV) ions, though electron delocalisation in this Kramers system cannot be definitively ruled out, and the resulting polarised-covalent U = C bonds are supported by iodide and δ-bonded arene bridges. The arenes provide reservoirs that accommodate charge, thus avoiding inter-electronic repulsion that would destabilise these low oxidation state metal-ligand multiple bonds. Using arenes as electronic buffers could constitute a general synthetic strategy by which to stabilise otherwise inherently unstable metal-ligand linkages.
Oxytocin and vasopressin flatten dominance hierarchy and enhance behavioral synchrony in part via anterior cingulate cortex
Authors: Jiang Yaoguang , Platt Michael L. 
Published: May 2018

AbstractThe neuropeptides oxytocin (OT) and arginine vasopressin (AVP) influence social functions in many mammals. In humans and rhesus macaques, OT delivered intranasally can promote prosocial behavior in certain contexts. Yet the precise neural mechanisms mediating these behavioral effects remain unclear. Here we show that treating a group of male macaque monkeys intranasally with aerosolized OT relaxes their spontaneous social interactions with other monkeys. OT reduces differences in social behavior between dominant and subordinate monkeys, thereby flattening the status hierarchy. OT also increases behavioral synchrony within a pair. Intranasal delivery of aerosolized AVP reproduces the effects of OT with greater efficacy. Remarkably, all behavioral effects are replicated when OT or AVP is injected focally into the anterior cingulate gyrus (ACCg), a brain area linked to empathy and other-regarding behavior. ACCg lacks OT receptors but is rich in AVP receptors, suggesting exogenous OT may shape social behavior, in part, via nonspecific binding. Notably, OT and AVP alter behaviors of both the treated monkey and his untreated partner, consistent with enhanced feedback through reciprocal social interactions. These findings bear important implications for use of OT in both basic research and as a therapy for social impairments in neurodevelopmental disorders.