bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating pro- and anti-angiogenic factors in multi-stage liver disease and hepatocellular carcinoma progression
Authors: Joo Yu Young , Jang Jeong Won , Lee Sung Won , Yoo Sun Hong , Kwon Jung Hyun , Nam Soon Woo , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew 
Published: June 2019

AbstractTo date, few studies have carried out a simultaneous determination of multiple pro- and anti-angiogenic factors during liver diseases progression. This study investigated the dynamic change in circulating angiogenic factors in multi-step carcinogenesis and hepatocellular carcinoma (HCC) progression. Serum levels of major pro-angiogenic [Vascular endothelial growth factor (VEGF), Basic fibroblast growth factor (b-FGF)] and anti-angiogenic [Thrombospondin-1 (TSP-1), Endostatin] factors were identified by enzyme-linked immunosorbent assay and correlated with liver diseases progression and outcomes of HCC patients undergoing transarterial chemo-embolization. A total of 240 patients (156 HCC, 37 cirrhosis and 47 chronic hepatitis) were enrolled in this study. While progressing from chronic hepatitis, cirrhosis to HCC, VEGF and b-FGF levels showed a significant change. Particularly, b-FGF yielded the highest AUROC value for a diagnosis of HCC and its distinction from other disease groups. A trend towards increasing VEGF levels was observed from Child-Pugh class A, B to C. VEGF and TSP-1 levels increased with the advance of cancer stage, with a remarkable increase in TSP-1 at an intermediate stage. Pretreatment levels of VEGF, TSP-1, and endostatin independently predicted the overall survival of patients. VEGF and TSP-1 levels correlated with progression-free survival. Our study demonstrated the dynamic angiogenic switch and the roles that individual pro- and anti-angiogenic factors contribute to carcinogenesis and HCC progression during the course of multi-step liver diseases. These imply the future possibility of testing pro- and anti-angiogenic panels as a diagnostic marker and a guide in decision-making about upcoming targeted therapies.
Caffeine exposure induces browning features in adipose tissue in vitro and in vivo
Authors: Velickovic Ksenija , Wayne Declan , Leija Hilda Anaid Lugo , Bloor Ian , Morris David E. , Law James , Budge Helen , Sacks Harold , Symonds Michael E. , Sottile Virginie 
Published: June 2019

AbstractBrown adipose tissue (BAT) is able to rapidly generate heat and metabolise macronutrients, such as glucose and lipids, through activation of mitochondrial uncoupling protein 1 (UCP1). Diet can modulate UCP1 function but the capacity of individual nutrients to promote the abundance and activity of UCP1 is not well established. Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown. This study examined the effect of caffeine on BAT thermogenesis in vitro and in vivo. Stem cell-derived adipocytes exposed to caffeine (1 mM) showed increased UCP1 protein abundance and cell metabolism with enhanced oxygen consumption and proton leak. These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content. Caffeine also increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression and mitochondrial biogenesis, together with a number of BAT selective and beige gene markers. In vivo, drinking coffee (but not water) stimulated the temperature of the supraclavicular region, which co-locates to the main region of BAT in adult humans, and is indicative of thermogenesis. Taken together, these results demonstrate that caffeine can promote BAT function at thermoneutrality and may have the potential to be used therapeutically in adult humans.
Tau is required for the function of extrasynaptic NMDA receptors
Authors: Pallas-Bazarra Noemí , Draffin Jonathan , Cuadros Raquel , Antonio Esteban José , Avila Jesús 
Published: June 2019

AbstractTau is a microtubule-associated neuronal protein found mainly in axons. However, increasing evidence indicates that it is also present in dendrites, where it serves as an essential mediator of synaptic NMDA (N-methyl-D-aspartate) receptor-dependent excitotoxicity. Of note, NMDA receptors can also be found outside synapses in the plasma membrane, and activation of extrasynaptic NMDA receptors has been shown to be more linked to excitotoxicity than the activation of synaptic ones. Little is known about the role of Tau in the activity of extrasynaptic NMDA receptors. Thus, we have used a Tau knockout mouse model (Tau−/− mice) to analyze the consequences of Tau absence in extrasynaptic NMDA receptor activity. We demonstrate that absence of Tau leads to a decrease in functional extrasynaptic NMDA receptors in the hippocampus. We propose that this impairment in extrasynaptic NMDA receptor activity may contribute to the well-known neuroprotective effect associated with Tau deficiency under pathological conditions.
Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics
Authors: Tyagi Rahul , Elfawal Mostafa A. , Wildman Scott A. , Helander Jon , Bulman Christina A. , Sakanari Judy , Rosa Bruce A. , Brindley Paul J. , Janetka James W. , Aroian Raffi V. , Mitreva Makedonka 
Published: June 2019

AbstractTargeting chokepoint enzymes in metabolic pathways has led to new drugs for cancers, autoimmune disorders and infectious diseases. This is also a cornerstone approach for discovery and development of anthelmintics against nematode and flatworm parasites. Here, we performed omics-driven knowledge-based identification of chokepoint enzymes as anthelmintic targets. We prioritized 10 of 186 phylogenetically conserved chokepoint enzymes and undertook a target class repurposing approach to test and identify new small molecules with broad spectrum anthelmintic activity. First, we identified and tested 94 commercially available compounds using an in vitro phenotypic assay, and discovered 11 hits that inhibited nematode motility. Based on these findings, we performed chemogenomic screening and tested 32 additional compounds, identifying 6 more active hits. Overall, 6 intestinal (single-species), 5 potential pan-intestinal (whipworm and hookworm) and 6 pan-Phylum Nematoda (intestinal and filarial species) small molecule inhibitors were identified, including multiple azoles, Tadalafil and Torin-1. The active hit compounds targeted three different target classes in humans, which are involved in various pathways, including carbohydrate, amino acid and nucleotide metabolism. Last, using representative inhibitors from each target class, we demonstrated in vivo efficacy characterized by negative effects on parasite fecundity in hamsters infected with hookworms.
Unraveling the role of the CbrA histidine kinase in the signal transduction of the CbrAB two-component system in Pseudomonas putida
Authors: Monteagudo-Cascales Elizabet , García-Mauriño Sofía M. , Santero Eduardo , Canosa Inés 
Published: June 2019

AbstractThe histidine kinase CbrA of the CbrAB two-component system of Pseudomonas putida is a key element to recognise the activating signal and mediate auto- and trans-phosphorylation of the response element CbrB. CbrA is encoded by the gene cbrA which is located downstream of a putative open reading frame we have named cbrX. We describe the role of the CbrX product in the expression of CbrA and show there is translational coupling of the genes. We also explore the role of the transmembrane (TM) and PAS domains of CbrA in the signal recognition. A ΔcbrXA mutant lacking its TM domains is uncoupled in its growth in histidine and citrate as carbon sources, but its overexpression restores the ability to grow in such carbon sources. In these conditions ΔTM-CbrA is able to respond to carbon availability, thus suggesting an intracellular nature for the signal sensed.
Self-assembled Cube-like Copper Oxide Derived from a Metal-Organic Framework as a High-Performance Electrochemical Supercapacitive Electrode Material
Authors: Aljaafari Abdullah , Parveen Nazish , Ahmad Faheem , Alam Mir Waqas , Ansari Sajid Ali 
Published: June 2019

AbstractInterest in pseudocapacitive materials, especially cuprous oxide, has grown owing to its various advantageous properties and application as electrode materials in the energy storage devices. The work presented here, a cubic Cu2O framework was synthesized using a simple and one-step modified polyol-assisted (metal-organic framework) solvothermal method. The structural configuration was rationalized by systematically studying the effect of the reaction time on the morphology and growth of the Cu2O. In addition, a range of microscopic and spectroscopic techniques was employed to further characterize the obtained cubic Cu2O. The morphological effect on the electrochemical supercapacitive performance of the obtained cubic Cu2O was also examined by cyclic-voltammetry (CV) and galvanostatic-charge-discharge (G-C-D) method. The obtained outcome shows that the cubic Cu2O synthesized using a reaction time of 12 h (Cu2O-12h; Csp~365 Fg−1) exhibited superior capacitive performance as compared to the cubic Cu2O synthesized at 8 h (Cu2O-8h; Csp~151 Fg−1) and 10 h (Cu2O-10h; Csp~195 Fg−1) at the current density of 0.75 Ag−1. Furthermore, the Cu2O-12h electrode exhibits energy density of 16.95 Wh/Kg at a power density of 235.4 W/Kg and higher power density of 2678.5 W/Kg at low current density. In particular, the cube-like Cu2O-12h exhibited excellent capacitive performance and rate capability as compared to Cu2O-8h and Cu2O-10h, owing to its unique three-dimensional morphology, which facilitates the formation of various active sites for intercalation of the electrolyte during the electrochemical process. These results show the as-obtained Cu2O could be a promising supercapacaitive electrode material for various applications.
CDK inhibitors reduce cell proliferation and reverse hypoxia-induced metastasis of neuroblastoma tumours in a chick embryo model
Authors: Swadi Rasha R. , Sampat Keerthika , Herrmann Anne , Losty Paul D. , See Violaine , Moss Diana J. 
Published: June 2019

AbstractNeuroblastoma is a paediatric cancer with a poor prognosis. This is in part due to widespread metastasis at time of presentation, which is refractory to current treatment modalities. New therapeutic agents that can control not only tumour growth but also metastasis are urgently needed. The differentiation therapy, retinoic acid, is currently used in clinic, leading to terminal differentiation of neuroblastoma cells thus reducing tumour growth in the primary tumour as well as at metastatic sites. However, retinoic acid only works in a subset of patients. We investigated the potential of CDK inhibitors, Palbociclib and RO-3306, on neuroblastoma cell differentiation, tumour progression and metastasis by utilising a 3R compliant cost effective preclinical chick embryo model. In both SK-N-AS and BE(2)C cell lines, when engrafted on the chorioallantoic membrane of chick embryos, we observed a reduction of tumour cell proliferation as well as a reduction in hypoxia preconditioning-driven metastasis by 60%. In addition, the expression of a panel of genes with known roles in metastasis, which increased upon hypoxia-preconditioning, was largely reduced by a CDK1 inhibitor. These results provide a promising alternative to currently existing therapies and might aid the development of new treatment protocols for retinoic acid-resistant patients.
Low-diluted Phenacetinum disrupted the melanoma cancer cell migration
Authors: Fuselier Camille , Terryn Christine , Berquand Alexandre , Crowet Jean-Marc , Bonnomet Arnaud , Molinari Michael , Dauchez Manuel , Martiny Laurent , Schneider Christophe 
Published: June 2019

AbstractDynamic and reciprocal interactions generated by the communication between tumor cells and their matrix microenvironment, play a major role in the progression of a tumor. Indeed, the adhesion of specific sites to matrix components, associated with the repeated and coordinated formation of membrane protrusions, allow tumor cells to move along a determined pathway. Our study analyzed the mechanism of action of low-dilutedPhenacetinumon murine cutaneous melanoma process in a fibronectin matrix environment. We demonstrated a reduction of dispersed cell migration, early and for as long as 24 h, by altering the formation of cell protrusions. Moreover, low-dilutedPhenacetinumdecreased cell stiffness highly on peripheral areas, due to a disruption of actin filaments located just under the plasma membrane. Finally, it modified the structure of the plasma membrane by accumulating large ordered lipid domains and disrupted B16 cell migration by a likely shift in the balance between ordered and disordered lipid phases. Whereas the correlation between the excess of lipid raft and cytoskeleton disrupting is not as yet established, it is clear that low-dilutedPhenacetinumacts on the actin cytoskeleton organization, as confirmed by a decrease of cell stiffness affecting ultimately the establishment of an effective migration process.
SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness
Authors: Nguyen Chi Huu , Glüxam Tobias , Schlerka Angela , Bauer Katharina , Grandits Alexander M. , Hackl Hubert , Dovey Oliver , Zöchbauer-Müller Sabine , Cooper Jonathan L. , Vassiliou George S. , Stoiber Dagmar , Wieser Rotraud , Heller Gerwin 
Published: June 2019

AbstractAcute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically.
Analysis of Side-band Inequivalence
Authors: Khorasani Sina 
Published: June 2019

AbstractFrequency shifts of red- and blue-scattered (Stokes/anti-Stokes) side-bands in quantum optomechanics are shown to be counter-intuitively inequal, resulting in an unexpected symmetry breaking. This difference is referred to as Side-band Inequivalenve (SI), which normally leans towards red, and being a nonlinear effect it depends on optical power or intracavity photon number. Also there exists a maximum attainable SI at an optimal operation point. The mathematical method employed here is a combination of operator algebra equipped with harmonic balance, which allows a clear understanding of the associated nonlinear process. This reveals the existence of three distinct operation regimes in terms of pump power, two of which have immeasurably small SI. Compelling evidence from various experiments sharing similar interaction Hamiltonians, including quantum optomechanics, ion/Paul traps, electrooptic modulation, Brillouin scattering, and Raman scattering unambiguously confirm existence of a previously unnoticed SI.
Stacking sequence variations in vaterite resolved by precession electron diffraction tomography using a unified superspace model
Authors: Steciuk Gwladys , Palatinus Lukáš , Rohlíček Jan , Ouhenia Salim , Chateigner Daniel 
Published: June 2019

AbstractAs a metastable phase, vaterite is involved in the first step of crystallization of several carbonate-forming systems including the two stable polymorphs calcite and aragonite. Its complete structural determination would consequently shed important light to understand scaling formation and biomineralization processes. While vaterite’s hexagonal substructure (a0 ~ 4.1 Å and c0 ~ 8.5 Å) and the organization of the carbonate groups within a single layer is known, conflicting interpretations regarding the stacking sequence remain and preclude the complete understanding of the structure. To resolve the ambiguities, we performed precession electron diffraction tomography (PEDT) to collect single crystal data from 100 K to the ambient temperature. The structure was solved ab initio and described over all the temperature range using a unified modulated structure model in the superspace group C12/c1(α0γ)00 with a = a0 = 4.086(3) Å, b = $$\sqrt{{\bf{3}}}$$

3

a0 = 7.089(9) Å, c = c0 = 8.439(9) Å, α = β = γ = 90° and q = $$\tfrac{{\bf{2}}}{{\bf{3}}}$$

2
3

a* + γc*. At 100 K the model presents a pure 4-layer stacking sequence with γ = $$\tfrac{{\bf{1}}}{{\bf{2}}}$$

1
2

whereas at the ambient temperature, ordered stacking faults are introduced leading to γ < $$\tfrac{{\bf{1}}}{{\bf{2}}}$$

1
2

. The model was refined against PEDT data using the dynamical refinement procedure including modulation and twinning as well as against x-ray powder data by the Rietveld refinement.
RETRACTED ARTICLE: Oscillations of the baseline of solar magnetic field and solar
irradiance on a millennial timescale
Authors: Zharkova V. V. , Shepherd S. J. , Zharkov S. I. , Popova E. 
Published: June 2019

AbstractRecently discovered long-term oscillations of the solar background
magnetic field associated with double dynamo waves generated in inner and outer
layers of the Sun indicate that the solar activity is heading in the next three
decades (2019–2055) to a Modern grand minimum similar to Maunder one. On the other
hand, a reconstruction of solar total irradiance suggests that since the Maunder
minimum there is an increase in the cycle-averaged total solar irradiance (TSI) by a
value of about 1–1.5 Wm−2 closely correlated with an increase
of the baseline (average) terrestrial temperature. In order to understand these two
opposite trends, we calculated the double dynamo summary curve of magnetic field
variations backward one hundred thousand years allowing us to confirm strong
oscillations of solar activity in regular (11 year) and recently reported grand
(350–400 year) solar cycles caused by actions of the double solar dynamo. In
addition, oscillations of the baseline (zero-line) of magnetic field with a period
of 1950 ± 95 years (a super-grand cycle) are discovered by applying a running
averaging filter to suppress large-scale oscillations of 11 year cycles. Latest
minimum of the baseline oscillations is found to coincide with the grand solar
minimum (the Maunder minimum) occurred before the current super-grand cycle start.
Since then the baseline magnitude became slowly increasing towards its maximum at
2600 to be followed by its decrease and minimum at ~3700. These oscillations of the
baseline solar magnetic field are found associated with a long-term solar inertial
motion about the barycenter of the solar system and closely linked to an increase of
solar irradiance and terrestrial temperature in the past two centuries. This trend
is anticipated to continue in the next six centuries that can lead to a further
natural increase of the terrestrial temperature by more than 2.5 °C by 2600.
HER3 targeting potentiates growth suppressive effects of the PI3K inhibitor BYL719 in pre-clinical models of head and neck squamous cell carcinoma
Authors: Meister Kara S. , Godse Neal R. , Khan Nayel I. , Hedberg Matthew L. , Kemp Carolyn , Kulkarni Sucheta , Alvarado Diego , LaVallee Theresa , Kim Seungwon , Grandis Jennifer R. , Duvvuri Umamaheswar 
Published: June 2019

AbstractBYL719 is a PI3K inhibitor that has demonstrated efficacy in the treatment of head and neck squamous cell carcinoma. BYL719 exerts its therapeutic effect by suppressing AKT and other proliferative signaling mechanisms. Despite PI3K inhibition and AKT suppression, residual activity of protein S6, a core marker of proliferative activation, has been observed. HER3, either via dimerization or activation by its ligand neurgeulin (NRG), is known to activate PI3K. Thus, we hypothesized that co-targeting HER3 and PI3K would lead to greater suppression of the PI3K-AKT signaling pathway and greater tumor suppression than with BYL719 alone. We investigated biochemical expression and activation of the HER3-PI3K-AKT-S6 pathway in HNSCC cell lines and patient-derived xenografts (PDXs). Antitumor effects of HER3 and PI3K inhibitors alone and in combination were evaluated in cell culture and murine models. Treatment of HNSCC cell lines with BYL719 significantly reduced AKT activation and suppressed tumor growth. However, S6 was persistently activated despite suppression of AKT. Combination treatment with KTN3379, a monoclonal antibody targeted against HER3, and BYL719 led to enhanced suppression of in vitro and in vivo cancer growth and durable suppression of AKT and S6. Therefore, inhibition of HER3 with KTN3379 enhanced the effects of PI3K inhibition in pre-clinical HNSCC models. These data support co-targeting HER3 and PI3K for the treatment of HSNCC.
Risk of osteoporosis in patients with chronic inflammatory neuropathy- a population-based cohort study
Authors: Kim Seung Woo , Kim Eun Hwa , Lee Jinae , Choi Young-Chul , Kim Seung Min , Shin Ha Young 
Published: June 2019

AbstractThe risk of osteoporosis in patients with chronic inflammatory neuropathy (CIN) has not been evaluated in detail. We conducted a population-based case-control study nested in a retrospective cohort to analyze osteoporosis risk among patients with CIN using a nationwide database. Patients with CIN based on the Korean Classification of Disease diagnostic code were included and were matched to controls. A Cox proportional hazards regression model was used to evaluate the effect of CIN on osteoporosis. After propensity score matching, 585 CIN patients and 585 controls were selected. Patients with CIN had an increased osteoporosis risk (hazard ratio [HR] = 2.293, 95% confidence interval [CI] 1.460–3.601) compared with controls. The osteoporosis risk was higher among male patients with CIN than among male controls (HR = 5.404, 95% CI 2.252–12.969), while there were no significant differences among women. Among the CIN patients, the average daily dose of corticosteroids was higher in those who developed osteoporosis (19.6 mg [10.8–49.3]) than those who did not (16.2 mg [7.2–29.1], p = 0.001). The osteoporosis risk among CIN patients is higher than among controls. High risk of osteoporosis in male patients may indicate that osteoporosis in CIN patients results from the disease itself or related treatments.