bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanomolar Inhibitors of Trypanosoma brucei RNA Triphosphatase
Authors: Smith Paul , Ho C. Kiong , Takagi Yuko , Djaballah Hakim , Shuman Stewart
Published: June 2017

Eukaryal taxa differ with respect to the structure and mechanism of the RNA triphosphatase (RTPase) component of the mRNA capping apparatus. Protozoa, fungi, and certain DNA viruses have a metal-dependent RTPase that belongs to the triphosphate tunnel metalloenzyme (TTM) superfamily. Because the structures, active sites, and chemical mechanisms of the TTM-type RTPases differ from those of mammalian RTPases, the TTM RTPases are potential targets for antiprotozoal, antifungal, and antiviral drug discovery. Here, we employed RNA interference (RNAi) knockdown methods to show that
Trypanosoma brucei
RTPase Cet1 (TbCet1) is necessary for proliferation of procyclic cells in culture. We then conducted a high-throughput biochemical screen for small-molecule inhibitors of the phosphohydrolase activity of TbCet1. We identified several classes of chemicals—including chlorogenic acids, phenolic glycopyranosides, flavonoids, and other phenolics—that inhibit TbCet1 with nanomolar to low-micromolar 50% inhibitory concentrations (IC
50
s). We confirmed the activity of these compounds, and tested various analogs thereof, by direct manual assays of TbCet1 phosphohydrolase activity. The most potent nanomolar inhibitors included tetracaffeoylquinic acid, 5-galloylgalloylquinic acid, pentagalloylglucose, rosmarinic acid, and miquelianin. TbCet1 inhibitors were less active (or inactive) against the orthologous TTM-type RTPases of mimivirus, baculovirus, and budding yeast (
Saccharomyces cerevisiae
). Our results affirm that a TTM RTPase is subject to potent inhibition by small molecules, with the caveat that parallel screens against TTM RTPases from multiple different pathogens may be required to fully probe the chemical space of TTM inhibition.

IMPORTANCE
The stark differences between the structure and mechanism of the RNA triphosphatase (RTPase) component of the mRNA capping apparatus in pathogenic protozoa, fungi, and viruses and those of their metazoan hosts highlight RTPase as a target for anti-infective drug discovery. Protozoan, fungal, and DNA virus RTPases belong to the triphosphate tunnel metalloenzyme family. This study shows that a protozoan RTPase, TbCet1 from
Trypanosoma brucei
, is essential for growth of the parasite in culture and identifies, via
in vitro
screening of chemical libraries, several classes of potent small-molecule inhibitors of TbCet1 phosphohydrolase activity.
Do not treat the numbers: lithium toxicity
Authors: Foulser Peter , Abbasi Yasmin , Mathilakath Anand , Nilforooshan Ramin
Published: June 2017

We describe the case of a 62-year-old man with a history of bipolar disorder, previously stable on lithium for over 20 years, who presented with a manic relapse and signs of lithium toxicity in the form of a coarse tremor. Serum lithium levels were in the normal range, and the patient had stage 3 chronic kidney disease. He was admitted for treatment under Section 2 of the Mental Health Act, and after stopping lithium was started on olanzapine. Signs of lithium toxicity improved after withdrawal of lithium. This case highlights the need to treat normal serum lithium levels with caution in patients showing signs of clinical lithium toxicity.
Evolution of inhomogeneous LTB geometry with tilted congruence and modified gravity
Authors: Yousaf Z. , Bhatti M. Zaeem-ul-Haq , Rafaqat Aamna
Published: June 2017

The goal of this paper is to shed some light on the significance of congruence of observers, which seems to affect the dynamics of the universe under Palatini f(R) formalism. Starting by setting up the formalism needed, we have explored the field equations using Lemaitre–Tolman–Bondi geometry as an interior metric. We have formulated the relationship between the matter variables as seen by the observers in both co-moving and non-co-moving frames. The dynamical equations are evaluated to study the dynamics of inhomogeneous universe by exploring conservation equations along with the Ellis equations. We have also explored a collapsing factor describing the bouncing phenomena via transport equation and conclude the stability region.
Chiral fermions on 2D curved space–times
Authors: Loran Farhang
Published: June 2017

The theory of free Majorana–Weyl spinors is the prototype of conformal field theory in two dimensions in which the gravitational anomaly and the Weyl anomaly obstruct extending the flat space–time results to curved backgrounds. In this paper, we investigate a quantization scheme in which the short distance singularity in the two-point function of chiral fermions on a two-dimensional curved space–time is given by the Green’s function corresponding to the classical field equation. We compute the singular term in the Green’s function explicitly and observe that the short distance limit is not well-defined in general. We identify constraints on the geometry which are necessary to resolve this problem. On such special backgrounds, the theory has locally [Formula: see text] conformal symmetry.
Two-diode behavior in metal-ferroelectric-semiconductor structures with bismuth titanate interfacial layer
Authors: Durmuş Perihan , Altindal Şemsettin
Published: June 2017

In this study, electrical parameters of the Al/Bi4Ti3O[Formula: see text]/p-Si metal-ferroelectric-semiconductor (MFS) structure and their temperature dependence were investigated using current–voltage (I–V) data measured between 120 K and 300 K. Semi-logarithmic I–V plots of the structure revealed that fabricated structure presents two-diode behavior that leads to two sets of ideality factor, reverse saturation current and zero-bias barrier height (BH) values. Obtained results of these parameters suggest that current conduction mechanism (CCM) deviates strongly from thermionic emission theory particularly at low temperatures. High values of interface states and nkT/q[Formula: see text]−[Formula: see text]kT/q plot supported the idea of deviation from thermionic emission. In addition, [Formula: see text](I)[Formula: see text]−[Formula: see text][Formula: see text](V) plots suggested that CCM varies from one bias region to another and depends on temperature as well. Series resistance values were calculated using Ohm’s law and Cheungs’ functions, and they decreased drastically with increasing temperature.
Universality of small black hole instability in AdS/CFT
Authors: Buchel Alex
Published: June 2017

[Formula: see text] Type IIb supergravity compactifications on five-dimensional Einstein manifolds [Formula: see text] realize holographic duals to four-dimensional conformal field theories. Black holes in such geometries are dual to thermal states in these CFTs. When black holes become sufficiently small in (global) [Formula: see text], they are expected to suffer Gregory–Laflamme instability with respect to localization on [Formula: see text]. Previously, the instability was demonstrated for gravitational dual of [Formula: see text] SYM, where [Formula: see text]. We extend stability analysis to arbitrary [Formula: see text]. We point out that the quasinormal mode equation governing the instabilities is universal. The precise onset of the instability is [Formula: see text]-sensitive, as it is governed by the lowest nonvanishing eigenvalue [Formula: see text] of its Laplacian.
BEHAVIORS OF PHOTOCONDUCTIVE DETECTORS BASED ON MAPbI3 PEROVSKITE FILMS
Authors: YU GENYUAN , FENG LISHA , MENG LU , YE ZHIZHEN , LU JIANGUO
Published: June 2017

The CH3NH3PbI3 films were synthesized by a facile low-cost solution process and were used to fabricate photoconductive detectors. The perovskite photodetector is very sensitive to light, with a high responsivity of 5.51[Formula: see text]mA/W and a sensitivity of 50 at 5[Formula: see text]V under 350[Formula: see text]nm light illumination. The device exhibits the fast rise and decay processes with similar appearance, and the relaxation time constants are 270 and 300[Formula: see text]ms, respectively. The photo-current shows an evident saturation, without further increase for prolonging the illumination period. The perovskite photodetectors display high responsive performances to short-wavelength lights. This study is expected to provide a fundamental knowledge of perovskite photodetectors with high speed and repeatability for practical applications.
Synthesis, Characterization and Reactivity of Nanostructured Zero-Valent Iron Particles for Degradation of Azo Dyes
Authors: Mikhailov Ivan , Levina Vera , Leybo Denis , Masov Vsevolod , Tagirov Marat , Kuznetsov Denis
Published: June 2017

Nanostructured zero-valent iron (NSZVI) particles were synthesized by the method of ferric ion reduction with sodium borohydride with subsequent drying and passivation at room temperature in technical grade nitrogen. The obtained sample was characterized by means of X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy and dynamic light scattering studies. The prepared NSZVI particles represent 100–200[Formula: see text]nm aggregates, which consist of 20–30[Formula: see text]nm iron nanoparticles in zero-valent oxidation state covered by thin oxide shell. The reactivity of the NSZVI sample, as the removal efficiency of refractory azo dyes, was investigated in this study. Two azo dye compounds, namely, orange G and methyl orange, are commonly detected in waste water of textile production. Experimental variables such as NSZVI dosage, initial dye concentration and solution pH were investigated. The kinetic rates of degradation of both dyes by NSZVI increased with the decrease of solution pH from 10 to 3 and with the increase of NSZVI dosage, but decreased with the increase of initial dye concentration. The removal efficiencies achieved for both orange G and methyl orange were higher than 90% after 80[Formula: see text]min of treatment.
Synthesis, Structural, Optical and Dielectric Studies on Carbon Dot-Zinc Oxide Nanocomplexes
Authors: Sundar S. Ajin , John N. Joseph
Published: June 2017

In the present manuscript, we have reported the synthesis, structural, optical, AC conductivity and dielectric studies of carbon dot-zinc oxide (CDZO) nanocomplexes. CDZO nanocomplexes were synthesized by the wet chemical method. The refinement of X-ray powder diffraction data reveals that the sample possesses hexagonal structure of ZnO. The low intensity diffraction peaks corresponding to carbon come to existence, it is suggested that phase segregation has occurred in the CDZO nanoparticles. The strong absorption band observed in the UV region for the prepared samples can be attributed to the band edge absorption. Dielectric property and AC conductivity have been studied as a function of frequency (100[Formula: see text]Hz and 1[Formula: see text]kHz) of the applied AC signal in the temperature range 30[Formula: see text]C to 150[Formula: see text]C. The result showed that AC conductivity increases with increase of temperature. Dielectric loss and DC conductivity increase with increase of temperature.
Simultaneous Signal Amplification and Clock Distribution Employing Backward Raman Pump Over an Optical Fiber for Applications Such as Square Kilometer Array
Authors: Rotich Kipnoo E. K. , Gamatham R. R. G. , Leitch A. W. R. , Gibbon T. B.
Published: June 2017

For the first time to our knowledge, we experimentally demonstrate a clock signal transmission using a counter-propagating Raman pump as a transmitter and concurrently utilize the same pump to amplify a data signal. A 1548[Formula: see text]nm vertical cavity surface emitting laser (VCSEL) was modulated with a pseudorandom bit sequence (2[Formula: see text]) and coupled into an optical fiber. A 1448[Formula: see text]nm Raman pump in the backward scheme was also modulated with a 10[Formula: see text]kHz clock and used to boost the VCSEL data signal so as to improve the reach of the transmission. Clock distribution in a telescope network such as the Square Kilometre Array (SKA) is essential for the proper operation of the digitizers as well as dish synchronization. In the SKA phase 1, long transmissions involving baselines extending up to 100[Formula: see text]km may need amplification. We propose the use of counter-Raman configuration to amplify the signal carrying received astronomical data while transmitting a clock to the receptors. This is a cost-effective bi-directional transmission suited for telescope network applications.
Catchment-based gold prospectivity analysis combining geochemical, geophysical and geological data across northern Australia
Authors: Cracknell M. J. , de Caritat P.
Published: June 2017

The results of a pilot study into the application of an unsupervised clustering approach to the analysis of catchment-based National Geochemical Survey of Australia (NGSA) geochemical data combined with geophysical and geological data across northern Australia are documented. NGSA Mobile Metal Ion® (MMI) element concentrations and first and second order statistical summaries across catchments of geophysical data and geological data are integrated and analysed using Self-Organizing Maps (SOM). Input features that contribute significantly to the separation of catchment clusters are objectively identified and assessed.

A case study of the application of SOM for assessing the spatial relationships between Au mines and mineral occurrences in catchment clusters is presented. Catchments with high mean Au code-vector concentrations are found downstream of areas known to host Au mineralization. This knowledge is used to identify upstream catchments exhibiting geophysical and geological features that indicate likely Au mineralization. The approach documented here suggests that catchment-based geochemical data and summaries of geophysical and geological data can be combined to highlight areas that potentially host previously unrecognised Au mineralization.
Geochemical and mineralogical characterization of tailings of the Dexing copper mine, Jiangxi Province, China
Authors: Pan Hanjiang , Cheng Zhizhong , Zhou Guohua , Yang Rong , Sun Binbin , He Ling , Zeng Daoming , Wang Jing
Published: June 2017

The Dexing copper mine is the largest open pit copper mines in Asia, with mining and beneficiation history stretching back more than half a century; consequently it has large amounts of ore tailings. The mineralogy, chemical composition and distribution of elements in the impounded tailings are of great significance to the future utilization and reclamation of the tailings ponds. In total, 1400 tailing samples from 35 drill cores were collected from the 1 tailings pond at the Dexing copper mine. All samples were analyzed to determine their chemical composition. The particle size, XRD, pH and sequential extraction fractions of selected samples were determined. The silt-size fraction dominates the grain-size distribution. Quartz and sericite are the most abundant gangue minerals in the tailings, with medians of 54.3 and 23.7%, respectively. 3D modeling of the tailings pond suggests that the distribution of particle size, minerals and elements is mainly controlled by the gravitational separation during tailings discharge. Silica, Cu, Mo and Ti are enriched in the dam area of the tailings pond, whereas Al
2
O
3
and K
2
O are enriched in the impoundment area. The potential Cu, Ti and sericite reserves in the tailings pond were estimated at 38 149 tons, 142 175 tons and 8.15 million tons, respectively. The tailings are not significantly oxidized and so their environmental risk is low under the present circumstances. Their weak alkalinity and presence of carbonate minerals provide the tailings buffering capacity to weak acids. Sequential extraction data suggest that the mobility of elements in the tailings pond is low; however, about 6040 tons of Cu, 428 tons of Zn, 252 tons of Mo, 145 tons of As and 66 tons of Pb, may be released if the physicochemical conditions change and the tailings become acidic.
Elastin receptor (S-gal) occupancy by elastin peptides modulates T-cell response during murine emphysema
Authors: Meghraoui-Kheddar Aïda , Pierre Alexandre , Sellami Mehdi , Audonnet Sandra , Lemaire Flora , Le Naour Richard
Published: June 2017

Chronic obstructive pulmonary disease and emphysema are associated with increased elastin peptides (EP) production because of excessive breakdown of lung connective tissue. We recently reported that exposure of mice to EP elicited hallmark features of emphysema. EP effects are largely mediated through a receptor complex that includes the elastin-binding protein spliced-galactosidase (S-gal). In previous studies, we established a correlation between cytokine production and S-gal protein expression in EP-treated immune cells. In this study, we investigated the S-gal-dependent EP effects on T-helper (Th) and T-cytotoxic (Tc) responses during murine EP-triggered pulmonary inflammation. C57BL/6J mice were endotracheally instilled with the valine-glycine-valine-alanine-proline-glycine (VGVAPG) elastin peptide, and, 21 days after treatment, local and systemic T-lymphocyte phenotypes were analyzed at cytokine and transcription factor expression levels by multicolor flow cytometry. Exposure of mice to the VGVAPG peptide resulted in a significant increase in the proportion of the CD4+ and CD8+ T cells expressing the cytokines IFN-γ or IL-17a and the transcription factors T-box expressed in T cells or retinoic acid-related orphan receptor-γt (RORγt) without effects on IL-4 and Gata-binding protein 3 to DNA sequence [A/T]GATA[A/G] expression. These effects were maximized when each T-cell subpopulation was challenged ex vivo with EP, and they were inhibited in vivo when an analogous peptide antagonizing the EP/S-gal interactions was instilled together with the VGVAPG peptide. This study demonstrates that, during murine emphysema, EP-S-gal interactions contribute to a Th-1 and Th-17 proinflammatory T-cell response combined with a Tc-1 response. Our study also highlights the S-gal receptor as a putative pharmacological target to modulate such an immune response.
Tumor-targeted Nanoparticle Delivery of HuR siRNA Inhibits Lung Tumor Growth In Vitro and In Vivo By Disrupting the Oncogenic Activity of the RNA-binding Protein HuR
Authors: Muralidharan Ranganayaki , Babu Anish , Amreddy Narsireddy , Srivastava Akhil , Chen Allshine , Zhao Yan Daniel , Kompella Uday B. , Munshi Anupama , Ramesh Rajagopal
Published: June 2017

Selective downregulation of the human antigen R (HuR) protein by siRNA may provide a powerful approach for treating lung cancer. To this end, we investigated the efficacy of transferrin receptor-targeted liposomal nanoparticle-based HuR siRNA (HuR-TfNP) therapy and compared with control siRNA (C)-TfNP therapy both, in vitro and in vivo using lung cancer models. In vitro studies showed HuR-TfNP, but not C-TfNP, efficiently downregulated HuR and HuR-regulated proteins in A549, and HCC827 lung cancer cells, resulting in reduced cell viability, inhibition of cell migration and invasion, and induction of G1 cell-cycle arrest culminating in apoptosis. However, HuR-TfNP activity in normal MRC-9 lung fibroblasts was negligible. In vivo biodistribution study demonstrated that fluorescently labeled HuR-siRNA or ICG dye–loaded TfNP localized in tumor tissues. Efficacy studies showed intratumoral or intravenous administration of HuR-TfNP significantly inhibited A549 (>55% inhibition) and HCC827 (>45% inhibition) subcutaneous tumor growth compared with C-TfNP. Furthermore, HuR-TfNP treatment reduced HuR, Ki67, and CD31 expression and increased caspase-9 and PARP cleavage and TUNEL-positive staining indicative of apoptotic cell death in tumor tissues compared with C-TfNP treatment. The antitumor activity of HuR-TfNP was also observed in an A549-luc lung metastatic model, as significantly fewer tumor nodules (9.5 ± 3.1; P < 0.001; 88% inhibition) were observed in HuR-TfNP–treated group compared with the C-TfNP–treated group (77.7 ± 20.1). Significant reduction in HuR, Ki67, and CD31 expression was also observed in the tumor tissues of HuR-TfNP-treatment compared with C-TfNP treatment. Our findings highlight HuR-TfNP as a promising nanotherapeutic system for lung cancer treatment. Mol Cancer Ther; 16(8); 1470–86. ©2017 AACR.
Genetic Predictors of ≥5% Weight Loss by Multidisciplinary Advice to Severely Obese Subjects
Authors: Aller Erik E.J.G. , Mariman Edwin C.M. , Bouwman Freek G. , van Baak Marleen A.
Published: June 2017

Background: Weight loss success is determined by genetic factors, which may differ according to treatment strategy. Methods: From a multidisciplinary obesity treatment program involving dietary advice, psychological counseling, and increased physical activity, 587 subjects (68% female; 46.1 ± 12.4 years; BMI 39.9 ± 6.3) were recruited. At baseline, a blood sample was drawn for DNA isolation. Genotypes were determined for 30 polymorphisms in 25 candidate genes. The association between genotypes and weight loss was assessed after 3 months (short-term) and after 12 months of treatment (long-term). Weight loss was categorized as ≥5% or <5% of initial weight. Results: The G/G genotype of PLIN1 (rs2289487) and PLIN1 (rs2304795), the T/T genotype of PLIN1 (rs1052700), and the C/C genotype of MMP2 predicted ≥5% weight loss in the first 3 months. The C/G-G/G genotype of PPARγ (rs1801282) and the T/C genotype of TIMP4 (rs3755724) predicted ≥5% weight loss after 12 months. Subjects with the combination of PPARγ (rs1801282) C/G-G/G and TIMP4 (rs3755724) T/C lost even more weight. Conclusion: Polymorphisms in genes related to regulation of fat storage and structural adaptation of the adipocytes are predictors for weight loss success with different genes being relevant for short-term and long-term weight loss success.
PTPRO Promotes Oxidized Low-Density Lipoprotein Induced Oxidative Stress and Cell Apoptosis through Toll-Like Receptor 4/Nuclear Factor κB Pathway
Authors: Liang Caihong , Wang Xiaochen , Hu Jianping , Lian Xiaoqing , Zhu Tiantian , Zhang Hui , Gu Ning , Li Jun
Published: June 2017

Background/Aims: Critical roles of phosphatase receptor type O (PTPRO) and toll-like receptor 4 (TLR4) have been implicated in inflammation. However, little is known about their functional effects on atherosclerosis (AS). We aim to study their potential function in AS. Methods: An oxidized low-density lipoprotein (ox-LDL) induced AS model constructed with PTPRO over-expressing RAW264.7 cells and PTPRO knockout macrophages. Cell apoptosis was assayed by flow cytometry and fatty accumulation was evaluated by oil red staining. The production of ROS (reactive oxygen species), SOD (superoxide dismutase), MDA (malondialdehyde), TC (Triglyceride), and TG (total cholesterol) was evaluated. Western blot was performed to detect the expression of CD36, TLR4 and nuclear factor kB (NF-κB). Results: PTPRO expression was promoted in a dose-dependent and time-dependent manner following ox-LDL challenging. In PTPRO-over-expressing cells, CD36 expression and the level of oil-red staining, TC and TG were increased; ROS production, MDA and level of cell apoptosis were improved, but SOD was reduced. However, in PTPRO knockout cells opposite results were found. TLR4 and NF-κB/p65 phosphorylation was significantly enhanced in PTPRO over-expressing cells, while significantly down-regulated in PTPRO knockout cells. Conclusion: PTPRO plays ital roles in AS via promoting ox-LDL induced oxidative stress and cell apoptosis through TLR4/NF-κB pathway.
Protective Effects of MicroRNA-126 on Human Cardiac Microvascular Endothelial Cells Against Hypoxia/Reoxygenation-Induced Injury and Inflammatory Response by Activating PI3K/Akt/eNOS Signaling Pathway
Authors: Yang Hong-Hui , Chen Yan , Gao Chuan-Yu , Cui Zhen-Tian , Yao Jian-Min
Published: June 2017

Objective: This study explored the protective effects of the microRNA-126 (miR-126)-mediated PI3K/Akt/eNOS signaling pathway on human cardiac microvascular endothelial cells (HCMECs) against hypoxia/reoxygenation (H/R)-induced injury and the inflammatory response. Methods: Untreated HCMECs were selected for the control group. After H/R treatment and cell transfection, the HCMECs were assigned to the H/R, miR-126 mimic, mimic-negative control (NC), miR-126 inhibitor, inhibitor-NC, wortmannin (an inhibitor of PI3K) and miR-126 mimic + wortmannin groups. Super oxide dismutase (SOD), nitric oxide (NO), vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) were measured utilizing commercial kits. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to detect miR-126 expression and the mRNA and protein expression of inflammatory factors. Western blotting was used to determine the expression of key members in the PI3K/Akt/eNOS signaling pathway. ACCK-8 assay and flow cytometry were employed to examine cell proliferation and apoptosis, respectively. The angiogenic ability in each group was detected by the lumen formation test. Results: Compared to the control group, p/t-PI3K, p/t-Akt and p/t-eNOS expression, NO, VEGF and SOD levels, cell proliferation and in vitro lumen formation ability were decreased, while the ROS content, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α expression and cell apoptosis were significantly increased in the H/R, mimic-NC, miR-126 inhibitor, inhibitor-NC, wortmannin and miR-126 mimic + wortmannin groups. Additionally, in comparison with the H/R group, the miR-126 mimic group had elevated p/t-PI3K, p/t-Akt and p/t-eNOS expression, increased NO, VEGF and SOD contents, and strengthened cell proliferation and lumen formation abilities but also exhibited decreased ROS content, reduced IL-6, IL-10 and TNF-α expressions, and weakened cell apoptosis, while the miR-126 inhibitor and wortmannin group exhibited the opposite results. Furthermore, decreased p/t-PI3K, p/t-Akt and p/t-eNOS expressions, decreased NO, VEGF and SOD contents, cell proliferation and lumen formation abilities, as well as increased ROS content, increased IL-6, IL-10 and TNF-α expression, and increased cell apoptosis were observed in the miR-126 mimic + wortmannin group compared to themiR-126 mimic group. Conclusions: These findings indicated that miR-126 protects HCMECs from H/R-induced injury and inflammatory response by activating the PI3K/Akt/ eNOS signaling pathway.
Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule
Authors: Yu Dehai , Du Zhonghua , Li Wei , Chen Huaqiu , Ye Songgen , Hoffman Andrew R. , Cui Jiuwei , Hu Ji-Fan
Published: June 2017

Background/Aims: Adult T-cell leukemia/lymphoma (ATL) is a very aggressive T cell malignancy that carries a poor prognosis, primarily due to its resistance to chemotherapy and to life-threatening infectious complications. Interferon-alpha (IFNα) has been used in combination with the anti-retroviral drug zidovudine to treat patients with ATL. However, the efficacy of long-term therapy is significantly limited due to the systemic toxicity of IFNα. Methods: We utilized phage display library screening to identify short peptides that specifically bind to Jurkat T lymphocyte leukemia cells. By fusing the Jurkat-binding peptide to the C-terminus of IFNα, we constructed an engineered chimeric IFNα molecule (IFNP) for the treatment of ATL. Results: We found that IFNP exhibited significantly higher activity than wild type IFNα in inhibiting the growth of leukemia cells and inducing cell blockage at the G0/G1 phase. The synthetic IFNP molecule exerted its antitumor activity by upregulating the downstream genes involved in the STAT1 pathway and in apoptosis. Using a cell receptor binding assay, we showed that this Jurkat-binding peptide facilitated the binding affinity of IFNα to the cell surface type I IFN receptor. Conclusion: The isolated Jurkat-binding peptide significantly potentiates the therapeutic activity of IFNα in T lymphocyte leukemia cells. The engineered IFNP molecule may prove to a novel antitumor approach in the treatment of patients with ATL.
Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction
Authors: Chang Xinwen , Bian Yiding , He Qizhi , Yao Julei , Zhu Jingping , Wu Jinting , Wang Kai , Duan Tao
Published: June 2017

Aims: Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ9-tetrahydrocannabinol (THC), the major component of marijuana, on trophoblast function, placental development, and birth outcomes. Methods: The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC) staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3) were detected by western blot. Results: We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Conclusion: Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction.
PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors
Authors: Castaing-Berthou Audrey , Malet Nicole , Radojkovic Claudia , Cabou Cendrine , Gayral Stéphanie , Martinez Laurent Olivier , Laffargue Muriel
Published: June 2017

Background/Aims: High-density lipoproteins (HDL) exert multiple cardioprotective functions on the arterial wall, including the promotion of endothelial cell survival and proliferation. Among mechanism contributing to endothelial protection, it has been reported that apolipoprotein A-I (apoA-I), the major protein in HDL, binds and activates the endothelial ecto-F1-ATPase receptor. This generates extracellular ADP, which in turn promotes endothelial cell survival. In this study we aimed to further investigate the signaling pathway involved downstream of apoA-I-induced ecto-F1-ATPase activation. Methods: In human umbilical vein endothelial cells (HUVECs), pharmacological and gene silencing approaches were used to study pathways involved downstream ecto-F1-ATPase activation by apoA-I. Results: ApoA-I and HDL both induced Akt phosphorylation. F1-ATPase inhibitors such as inhibitory factor 1 and oligomycin completely blocked apoA-I-induced Akt phosphorylaton and significantly blocked HDL-induced phosphorylation, indicating that this signaling pathway is dependent on ecto-F1-ATPase activation by apoA-I. Further, we were able to specify roles for the P2Y1-ADPreceptor and the PI3Kβ isoform in this pathway since pharmacological inhibition and silencing of these proteins dramatically inhibited apoA-I-induced Akt phosphorylation and cell proliferation. Conclusion: Altogether, these data highlight a key role of the P2Y1/PI3Kβ axis in endothelial cell proliferation downstream of ecto-F1-ATPase activation by apoA-I. Pharmacological targeting of this pathway could represent a promising approach to enhance vascular endothelial protection.
Transverse microhardness of artificial teeth
Authors: Tamaki Regina , Iegami Carolina Mayumi , Uehara Priscila Nakasone , Furuyama Ricardo Jun , Ballester Rafael Yague
Published: June 2017

Objetivo: A dureza é tida como indicador de várias propriedades mecânicas de dentes artificiais, e relacionada a resistência ao desgaste. O objetivo foi mapear a microdureza de dentes artificiais de 9 marcas em função da profundidade. Método: foi medida a microdureza Knoop de segundos molares cortados num plano sagital em intervalos de 200 µm a partir da profundidade de 100 µm até 4700 µm, das marcas: Premium (Pr), Orthosit (Or), SR Postaris DCL (Po), Biotone (Bi), Artiplus IPN (Ar), VITA MFT (Vi), Natusdent (Na), Trilux (Tr) and Biolux (Bx). A ANOVA de medidas repetidas e o teste de Tukey (5%) analisaram os resultados. Resultados: A marca SR Orthosit PE apresentou a maior dureza (até a profundidade de 3,1 mm foi da ordem de 30 N/mm2), significativamente maior que todas as outras medidas realizadas (da ordem de 20 N/mm2). Conclusões: A dureza Knoop não evidenciou diferenças entre camadas para oito das nove marcas estudadas. Foi constatada diferente dureza entre a superfície e a região cervical para a marca SR Orthosit PE.
Keratoacanthoma associated to cutaneous horn manifestation: case report and difficulty of diagnosis
Authors: Curra Marina , Martins Marco Antonio Trevizani , Hildebrand Laura Campos , Munerato Maria Cristina , Filho Manoel Sant'Ana , Martins Manoela Domingues
Published: June 2017

Introdução: O corno cutâneo (CC) é uma projeção hiperceratótica cônica da pele. Uma ampla variedade de lesões podem ser encontrados com aspecto clínico de corno cutâneo, incluindo tumores malignos. Relato de caso: Relatamos um caso de paciente do sexo masculino, 77 anos de idade, apresentando uma lesão assintomática, com aspecto clínico da CC no lábio inferior. A hipótese de diagnóstico clínico foi de carcinoma espinocelular (CEC) e uma biópsia incisional foi realizada. A análise histopatológica revelou um ceratoacantoma e a lesão foi completamente removida. Em um ano de acompanhamento nenhuma recidiva foi observada. Discussão: CC raramente é acompanhada por ceratoacantoma. No entanto, ceratoacantoma mostra um maior grau de atipia nuclear do que CEC tornando a diferenciação de duas doenças muito difícil. Neste caso ressaltamos a importância do exame histopatológico para descartar malignidade.
Association between disc displacement without reduction and temporomandibular joint derangement observed on magnetic resonance imaging
Authors: Araujo Juliane Piragine , Dutra Marcelo Eduardo Pereira , Santos Karina Cecilia Panelli
Published: June 2017

O objetivo deste estudo foi avaliar possíveis associações entre os seguintes fatores: anatomia e posição do disco articular; morfologia da eminência articular e da cabeça da mandíbula; presença de derrame articular; mobilidade da cabeça da mandíbula; e inserção do músculo pterigoideo lateral. Foram avaliadas imagens de ressonância magnética de 33 articulações de pacientes sintomáticos. O disco articular foi classificado como normal, alongado ou dobrado; o deslocamento foi classificado como normal, lateral ou medial; a cabeça da mandíbula foi classificado como arredondado, convexo, achatado ou angulado; a eminência articular foi classificada como caixa, sigmoide, achatada ou deformada; a mobilidade da cabeça da mandíbula foi classificada como normal, hipomobilidade ou hipermobilidade; e o padrão de inserção do músculo pterigoideo lateral foi classificado como Tipo I, Tipo II ou Tipo III. As formas mais frequentes do disco articular, eminência articular e cabeça da mandíbula foram dobrado, achatada e achatado, respectivamente. Pode existir uma relação da mobilidade da ATM que tende a apresentar uma forma de disco normal (100%), hipomobilidade da ATM com forma do disco dobrado (48%); e hipermobilidade da ATM com forma de disco alongado (100%). A ressonância magnética permitiu a observação clara das estruturas articulares e não foi encontrada associação entre o padrão de inserção e a posição lateral do disco, a forma do disco e a forma da cabeça da mandíbula. Todos os casos em que o derrame articular estava presente estavam relacionados à hipomobilidade (100%).
Ameloblastic fibroma: a case report
Authors: Carvalho Eloisa Muller de , Horikawa Fernando Kendi , Guimaraes Letícia , Viveiros Stephanie Kenig , Lemos Celso Augusto , Araujo Juliane Piragine
Published: June 2017

Ameloblastic fibroma is a rare benign odontogenic tumor in which both the epithelial and ectomesenchymal components are neoplastic. A 24-year-old male patient was referred to the Stomatology Department presenting with difficulty to chew and swelling in the right posterior region of the mandible. The panoramic radiograph showed a well-circumscribed, unilocular radiolucent lesion with partially radiopaque borders involving first and second unerupted molars. Computed tomography imaging presented a hypodense image with well‑delimited isodense content, bulging cortical bones and absence of rupture. The patient underwent an incisional biopsy.  Microscopically, the lesion was composed of many mesenchymal tissue cells in strand form, arranged in cords, islands and nests of odontogenic epithelium; the diagnostic was ameloblastic fibroma. The patient was referred to the hospital for enucleation and curettage of the lesion and extraction of the associated teeth. After 8 months of follow-up, no recurrence was observed. This case emphasizes the importance of differential diagnosis, anatomopathological exam, and both clinical and imaging follow-up, since tumors of this type can recur and progress to malignancy.
Dichomeris Hübner, 1818 (Lepidoptera, Gelechiidae, Dichomeridinae) from Cambodia, including associated Chinese species
Authors: ZHAO SHENGNAN , PARK KYU-TEK , BAE YANG-SEOP , LI HOUHUN
Published: June 2017

In a faunal study of the micromoths in Cambodia, thirteen species of the genus Dichomeris (Gelechiidae, Dichomeridinae) are recognized, including associated Chinese species. Eight species are described as new: D. arcuata sp. nov., D. splendiptera sp. nov., D. samkosensis sp. nov., D. foliforma sp. nov., D. magnimacularis sp. nov., D. hainanensis sp. nov., D. cambodiensis sp. nov., D. acutivalvata sp. nov. Five species are newly recorded for Cambodia: D. orientis Park & Hodges, D. fuscusitis Li & Zheng, D. obsepta (Meyrick), D. microsphena Meyrick, and D. matsumurai Ponomarenko & Ueda. . Images of adults and genitalia are provided.
The Roles of Convection over the Western Maritime Continent and the Philippine Sea in Interannual Variability of Summer Rainfall over Southwest China
Authors: Jiang Xingwen , Shu Jianchuan , Wang Xin , Huang Xiaomei , Wu Qing
Published: June 2017

Floods and droughts hit southwest China (SWC) frequently, especially over the last decade. In this study, the dominant modes of summer rainfall anomalies over SWC on the interannual time scale and the possible causes are investigated. Interannual variability of the summer rainfall over SWC has two dominant modes. The first mode features rainfall increases over most of SWC except central Sichuan, and the second mode exhibits wet conditions in the north but dry conditions in the south. The suppressed convection over the Philippine Sea affects the first mode by inducing anomalous anticyclones over the western North Pacific and to the south of the Tibetan Plateau, which transport more water vapor to eastern Tibet and eastern SWC and hence favor above-normal rainfall there. The enhanced convection over the western Maritime Continent could generate similar atmospheric circulation anomalies associated with the suppressed convection over the Philippine Sea but with a northward shift, resulting in significant increases in rainfall over northeastern SWC but weak decreases in rainfall over southeastern SWC. As a result, the rainfall anomalies over SWC tend to be different between El Niño–Southern Oscillation decaying and developing phases because their different impacts on the convection over the Philippine Sea and the western Maritime Continent. Meanwhile, the sea surface temperature in the tropical southeastern Indian Ocean also plays an important role in variability of the rainfall over SWC because of its significant impact on the convection over the western Maritime Continent.
Schools as Surveilling Institutions? Paternal Incarceration, System Avoidance, and Parental Involvement in Schooling
Authors: Haskins Anna R. , Jacobsen Wade C.
Published: June 2017

Parents play important roles in their children’s lives, and parental involvement in elementary school in particular is meaningful for a range of child outcomes. Given the increasing number of school-aged children with incarcerated parents, this study explores the ways paternal incarceration is associated with mothers’ and fathers’ reports of home- and school-based involvement in schooling. Using Fragile Families Study data, we find that a father’s incarceration inhibits his school- and home-based involvement in schooling, but associations for maternal involvement are weaker. Results are robust to alternative specifications of incarceration that address concerns about selection and unobserved heterogeneity. Findings also hold across levels of father-child contact. We also conducted a test of the system avoidance mechanism and results suggest it partially explains reductions in school involvement for fathers following incarceration. Given the reoccurring interest in the interconnection between families and schools and how this translates into success, this study suggests that paternal incarceration is associated with lower parental involvement in schooling and highlights the role of system avoidance in this association. Attachment to social institutions like schools is quite consequential, and this work highlights another way mass incarceration influences social life in the United States.
Why Elites Love Authentic Lowbrow Culture: Overcoming High-Status Denigration with Outsider Art
Authors: Hahl Oliver , Zuckerman Ezra W. , Kim Minjae
Published: June 2017

We develop and test the idea that public appreciation for authentic lowbrow culture affords an effective way for certain elites to address feelings of authenticity-insecurity arising from “high status denigration” (Hahl and Zuckerman 2014). This argument, which builds on recent sociological research on the “search for authenticity” (e.g., Grazian 2005) and on Bourdieu’s (1993) notion of artistic “disinterestedness,” is validated through experiments with U.S. subjects in the context of “outsider” art (Fine 2004). The first study demonstrates that preference for lowbrow culture perceived to be authentic is higher when individuals feel insecure in their authenticity because they attained status in a context where extrinsic incentives are salient. The second study demonstrates that audiences perceive the members of erstwhile denigrated high-status categories to be more authentic if they consume lowbrow culture, but only if the cultural producer is perceived as authentic. We conclude by noting how this “authenticity-by-appreciation” effect might be complementary to distinction-seeking as a motivation for elite cultural omnivorousness, and we draw broader implications for when and why particular forms of culture are in demand.
The Recognizability and Localizability of Auditory Alarms: Setting Global Medical Device Standards
Authors: Edworthy Judy , Reid Scott , McDougall Siné , Edworthy Jonathan , Hall Stephanie , Bennett Danielle , Khan James , Pye Ellen
Published: June 2017

Objective

Four sets of eight audible alarms matching the functions specified in IEC 60601-1-8 were designed using known principles from auditory cognition with the intention that they would be more recognizable and localizable than those currently specified in the standard.

Background

The audible alarms associated with IEC 60601-1-8, a global medical device standard, are known to be difficult to learn and retain, and there have been many calls to update them. There are known principles of design and cognition that might form the basis of more readily recognizable alarms. There is also scope for improvement in the localizability of the existing alarms.

Method

Four alternative sets of alarms matched to the functions specified in IEC 60601-1-8 were tested for recognizability and localizability and compared with the alarms currently specified in the standard.

Results

With a single exception, all prototype sets of alarms outperformed the current IEC set on both recognizability and localizability. Within the prototype sets, auditory icons were the most easily recognized, but the other sets, using word rhythms and simple acoustic metaphors, were also more easily recognized than the current alarms. With the exception of one set, all prototype sets were also easier to localize.

Conclusion

Known auditory cognition and perception principles were successfully applied to an existing audible alarm problem.

Application

This work constitutes the first (benchmarking) phase of replacing the alarms currently specified in the standard. The design principles used for each set demonstrate the relative ease with which different alarm types can be recognized and localized.
Testicular Fibrous Hypoplasia in Cynomolgus Monkeys (Macaca fascicularis): An Incidental, Congenital Lesion
Authors: Pereira Bacares Marcia E. , Vemireddi Vimala , Creasy Dianne
Published: June 2017

Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin–stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11.0% of the monkeys examined and then rose to 26.1% in 2010 and 30.9% in 2011. Overall, the lesion was identified in 10.94% of Asian monkeys with the highest incidence in animals originating from China and Vietnam; severity ranged from minimal to severe and it occurred unilaterally (38.5%) and bilaterally (61.5%). In Mauritian monkeys, the lesion was predominantly minimal in severity, bilateral in distribution, and affected 6.6% of the animals examined. The lesion occurred regardless of sexual maturation status but when present in mature monkeys was often associated with cystic tubular atrophy of the seminiferous epithelium. Based on the morphological characteristics of the lesion and the unilateral/bilateral distribution, the lesion is considered to be a congenital or developmental abnormality.
Todo Mejora en el Ambiente
Authors: Ciszek Erica L.
Published: June 2017

Digital media present great potential for disseminating campaigns, connecting with constituencies, and creating spaces for connectivity. This article explores a contemporary digital media project, Todo Mejora México, considering how emerging technology affects activism. This research illustrates how activists mobilize digital media, localizing and vernacularizing an international effort. Through user-generated projects, activists harness the power of digital media to create a platform for storytelling, content curation, and distribution of alternative lesbian, gay, bisexual, or transgender discourses into the media landscape.
Environmentalists abide: Listening to whale music – 1965–1985
Authors: Ritts Max
Published: June 2017

Music can enrich geographical efforts to understand ideology as a lived experience. This paper explores the history of whale music – instrumental music that samples or thematizes whale sound. For environmentalists who came of age in the late 1960s, whale music fostered new interrogations about the identity of nature and the nature of identity, interrogations that reflected structural changes in North American society. To understand whale music’s surprising ideological power, I draw on Althusser’s formative idea of interpellation, and refine it with insights from Antonio Gramsci, John Mowitt, and Neil Smith. As examples from British Columbia’s Lower Mainland and California’s Bay Area reveal, whale music interpellated environmentalists, capturing the energies of predominantly white middle-class subjects eager to develop new relationships with nature. Whale music was not discovered, as its devotees proposed it was, but invented, through a combination of animal sounds, recording techniques, consumer trends, and ideologies of nature. It reveals environmentalism as a sonorous formation – a system that recruits listeners into sonically-mediated realms of thought, action, and subjectivity.