bluuebunny/crossref_metadata_2025_split huggingface dataset:
Choline kinase inhibitors EB-3D and EB-3P interferes with lipid homeostasis in HepG2 cells
Authors: Sola-Leyva Alberto , López-Cara Luisa C. , Ríos-Marco Pablo , Ríos Antonio , Marco Carmen , Carrasco-Jiménez María P. 
Published: March 2019

AbstractA full understanding of the molecular mechanism of action of choline kinase α (ChoKα) inhibitors at the cell level is essential for developing therapeutic and preventive approaches for cancer. The aim of the present study was to evaluate the effects of the ChoKα inhibitors EB-3D and EB-3P on lipid metabolism in HepG2 cells. We used [methyl-14C]choline, [1,2-14C]acetic acid and [2-3H]glycerol as exogenous precursors of the corresponding phospholipids and neutral lipids. [Methyl-14C]choline was also used to determine choline uptake. Protein levels were determined by Western blot. Ultrastructural alterations were investigated by transmission electron microscopy. In this work, we demonstrate that EB-3D and EB-3P interfere with phosphatidylcholine biosynthesis via both CDP-choline pathway and choline uptake by the cell. Moreover, the synthesis of both diacylglycerols and triacylglycerols was affected by cell exposure to both inhibitors. These effects were accompanied by a substantial decrease in cholesterol biosynthesis, as well as alterations in the expression of proteins related to cholesterol homeostasis. We also found that EB-3D and EB-3P lowered ChoKα protein levels. All these effects could be explained by the modulation of the AMP-activated protein kinase signalling pathway. We show that both inhibitors cause mitochondrial alteration and an endoplasmic reticulum stress response. EB-3D and EB-3P exert effects on ChoKα expression, AMPK activation, apoptosis, endoplasmic reticulum stress and lipid metabolism. Taken together, results show that EB-3D and EB-3P have potential anti-cancer activity through the deregulation of lipid metabolism.
The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism
Authors: Quintana-Gallardo Lucía , Martín-Benito Jaime , Marcilla Miguel , Espadas Guadalupe , Sabidó Eduard , Valpuesta José María 
Published: March 2019

AbstractSome molecular chaperones are involved not only in assisting the folding of proteins but also, given appropriate conditions, in their degradation. This is the case for Hsp70 and Hsp90 which, in concert with the cochaperone CHIP, direct their bound substrate to degradation through ubiquitination. We generated complexes between the chaperones (Hsp70 or Hsp90), the cochaperone CHIP and, as substrate, a p53 variant containing the GST protein (p53-TMGST). Both ternary complexes (Hsp70:p53-TMGST:CHIP and Hsp90:p53-TMGST:CHIP) ubiquitinated the substrate at a higher efficiency than in the absence of the chaperones. The 3D structures of the two complexes, obtained using a combination of cryoelectron microscopy and crosslinking mass spectrometry, showed the substrate located between the chaperone and the cochaperone, suggesting a ubiquitination mechanism in which the chaperone-bound substrate is presented to CHIP. These complexes are inherently flexible, which is important for the ubiquitination process.
Nuclear resonant scattering from 193Ir as a probe of the electronic and magnetic properties of iridates
Authors: Alexeev Pavel , Leupold Olaf , Sergueev Ilya , Herlitschke Marcus , McMorrow Desmond F. , Perry Robin S. , Hunter Emily C. , Röhlsberger Ralf , Wille Hans-Christian 
Published: March 2019

AbstractThe high brilliance of modern synchrotron radiation sources facilitates experiments with high-energy x-rays across a range of disciplines, including the study of the electronic and magnetic correlations using elastic and inelastic scattering techniques. Here we report on Nuclear Resonance Scattering at the 73 keV nuclear level in 193Ir. The transitions between the hyperfine split levels show an untypically high E2/M1 multi-polarity mixing ratio combined with an increased sensitivity to certain changes in the hyperfine field direction compared to non-mixing transitions. The method opens a new way for probing local magnetic and electronic properties of correlated materials containing iridium and provides novel insights into anisotropic magnetism in iridates. In particular, unexpected out-of-plane components of magnetic hyperfine fields and non-zero electric field gradients in Sr2IrO4 have been detected and attributed to the strong spin-orbit interaction in this iridate. Due to the high, 62% natural abundance of the 193Ir isotope, no isotopic enrichment of the samples is required, qualifying the method for a broad range of applications.
Resting state functional connectivity predictors of treatment response to electroconvulsive therapy in depression
Authors: Moreno-Ortega M. , Prudic J. , Rowny S. , Patel G. H. , Kangarlu A. , Lee S. , Grinband J. , Palomo T. , Perera T. , Glasser M. F. , Javitt D. C. 
Published: March 2019

AbstractThere is increasing focus on use of resting-state functional connectivity (RSFC) analyses to subtype depression and to predict treatment response. To date, identification of RSFC patterns associated with response to electroconvulsive therapy (ECT) remain limited, and focused on interactions between dorsal prefrontal and regions of the limbic or default-mode networks. Deficits in visual processing are reported in depression, however, RSFC with or within the visual network have not been explored in recent models of depression. Here, we support prior studies showing in a sample of 18 patients with depression that connectivity between dorsal prefrontal and regions of the limbic and default-mode networks serves as a significant predictor. In addition, however, we demonstrate that including visual connectivity measures greatly increases predictive power of the RSFC algorithm (>80% accuracy of remission). These exploratory results encourage further investigation into visual dysfunction in depression, and use of RSFC algorithms incorporating the visual network in prediction of response to both ECT and transcranial magnetic stimulation (TMS), offering a new framework for the development of RSFC-guided TMS interventions in depression.
Molecular quantification of Plasmodium parasite density from the blood retained in used RDTs
Authors: Robinson Ailie , Busula Annette O. , Muwanguzi Julian K. , Powers Stephen J. , Masiga Daniel K. , Bousema Teun , Takken Willem , de Boer Jetske G. , Logan James G. , Beshir Khalid B. , Sutherland Colin J. 
Published: March 2019

AbstractMost malaria-endemic countries are heavily reliant upon rapid diagnostic tests (RDT) for malaria case identification and treatment. RDT previously used for malaria diagnosis can subsequently be used for molecular assays, including qualitative assessment of parasite species present or the carriage of resistance markers, because parasite DNA can be extracted from the blood inside the RDT which remains preserved on the internal components. However, the quantification of parasite density has not previously been possible from used RDT. In this study, blood samples were collected from school-age children in Western Kenya, in the form of both dried blood spots on Whatman filter paper, and the blood spot that is dropped into rapid diagnostic tests during use. Having first validated a robotic DNA extraction method, the parasite density was determined from both types of sample by duplex qPCR, and across a range of densities. The methods showed good agreement. The preservation of both parasite and human DNA on the nitrocellulose membrane inside the RDT was stable even after more than one year’s storage. This presents a useful opportunity for researchers or clinicians wishing to gain greater information about the parasite populations that are being studied, without significant investment of resources.
Complementary medicine use during cancer treatment and potential herb-drug interactions from a cross-sectional study in an academic centre
Authors: Jermini Mégane , Dubois Julie , Rodondi Pierre-Yves , Zaman Khalil , Buclin Thierry , Csajka Chantal , Orcurto Angela , Rothuizen Laura E. 
Published: March 2019

AbstractComplementary medicine (CM) is used by one third to one half of cancer patients throughout the world. The objective of this study was to describe the prevalence of CM use and the potential for interactions with cancer treatments in an academic oncology centre. A cross-sectional study was conducted among patients undergoing current cancer treatment. Among 132 included patients, 56% had used CM since their cancer diagnosis and 45% were using CM during cancer treatment at the time of the survey. The main CM used were green tea (35%), herbal tea (35%), homeopathy (27%), dietary supplements (27%), and herbal medicines (27%). A small majority of patients (58%) spontaneously mentioned the use of CM to their oncologist. Of 42 identified combinations of concomitant use of biologically based CM and anticancer agents among the study patients, the potential for pharmacokinetic interactions of clinical relevance was not expected in 17 combinations (40%), hypothetical and deemed unlikely in 23 (55%), and of probable low clinical relevance in 2 (5%). Considering the high prevalence of CM use, active enquiries should be made by healthcare professionals to detect symptoms that may relate to CM tolerance and effects or that suggest interactions between CM and cancer treatments.
A New Network Feature Affects the Intervention Performance on Public Opinion Dynamic Networks
Authors: Wang Caiyun , Han Huawei , Han Jing 
Published: March 2019

AbstractThe neighborhood network structure plays an important role in the collective opinion of an opinion dynamic system. Does it also affect the intervention performance? To answer this question, we apply three intervention methods on an opinion dynamic model, the weighted DeGroot model, to change the convergent opinion value $$\bar{x}$$

x
¯

. And we define a new network feature Ω, called ‘network differential degree’, to measure how node degrees couple with influential values in the network, i.e., large Ω indicates nodes with high degree is more likely to couple with large influential value. We investigate the relationship between the intervention performance and the network differential degree Ω in the following three intervention cases: (1) add one special agent (shill) to connect to one normal agent; (2) add one edge between two normal agents; (3) add a number of edges among agents. Through simulations we find significant correlation between the intervention performance, i.e., $$|\Delta {\bar{x}}^{\ast }|$$
|

Δ

x
¯

⁎

|
(the maximum value of the change of convergent opinion value $$|\Delta \bar{x}|$$
|

Δ

x
¯

|
) and Ω in all three cases: the intervention performance $$|\Delta {\bar{x}}^{\ast }|$$
|

Δ

x
¯

⁎

|
is higher when Ω is smaller. So Ω could be used to predict how difficult it is to intervene and change the convergent opinion value of the weighted DeGroot model. Meanwhile, a theorem of adding one edge and an algorithm for adding optimal edges are given.
Influence of Climate Variability and Reservoir Operation on Streamflow in the Yangtze River
Authors: Chai Yuanfang , Li Yitian , Yang Yunping , Zhu Boyuan , Li Sixuan , Xu Can , Liu Congcong 
Published: March 2019

AbstractUnderstanding the effects of climate variability and reservoir operation on runoff is important for shipping, irrigation and water supply services, especially during extreme drought years. After the operation of the Three Gorges Dam (TGD) began, the discharge processes in the mid-lower reaches of the Yangtze River were completely different from those during the pre-dam period. The measured hydrological data and the Mike 11-HD model were used to estimate the contributions of the TGD operation and climate variability to the variation in discharge during extreme drought years. The results are as follows: under the effects of the TGD operation and extreme drought, the special phenomenon of a “positive discharge anomaly in drought season and negative discharge anomaly in flood season” occurred compared with the conditions in the pre-dam period. During the flood season, the contributions of climate variation (TGD operation) to the changes in streamflow from Yichang station to Datong station were 86.6% (13.4%) and 80.7% (19.7%) in 2006 and 64.8% (35.2%) and 71.3% (28.7%) in 2011. During the dry season, the values were 81.2% (18.8%) and 93.9% (6.1%) in 2006 and 59.9% (40.1%) and 72.9% (27.1%) in 2011. Clearly, climate variation was the main reason for the variation in seasonal runoff. Furthermore, even in the 156 m and 175 m impoundments, climate variation was the dominant factor.
Magnetic resonance imaging of brain cell water
Authors: Watanabe Takashi , Wang Xiaoqing , Tan Zhengguo , Frahm Jens 
Published: March 2019

AbstractIn the central nervous system of vertebrates, cell bodies of neurons are often assembled as nuclei or cellular layers that play specific roles as functional units. The purpose of this work was to selectively highlight such cell assemblies by magnetic resonance imaging using signals from water protons that are associated with intracellular paramagnetic ions, while saturating lipid-associated water protons as well as extracellular free water protons. Given the significant correlation between image signal intensity and water proton density, the high signal intensities observed for such cell assemblies must be attributed to their abundant paramagnetic-ion-associated water protons. In the hippocampal formation, the technique visualized cell assemblies that were so far not depicted in human in vivo. In the brainstem, the technique delineated noradrenergic neuron groups such as the locus coeruleus in human and mice in vivo. Their reduced magnetization-transfer ratios together with their prolonged relaxation times compared to other gray matter indicate that the source of their high signal intensity is not the presence of T1-shortening molecules, e.g., neuromelanin, but their high water content. Given the general absence of neuromelanin in noradrenergic neurons of rodents, their high signal intensity in mice in vivo further supports this view.
Kisspeptin/kisspeptin receptor system in pseudopregnant rabbit corpora lutea: presence and function
Authors: Maranesi Margherita , Petrucci Linda , Leonardi Leonardo , Bufalari Antonello , Parillo Francesco , Boiti Cristiano , Zerani Massimo 
Published: March 2019

AbstractKisspeptin (KiSS) and its related receptors (KiSS1R) have a critical role in the reproduction of mammals. The KiSS/KiSS1R system is expressed in numerous reproductive organs including the ovary. Here, we studied the expression of the KiSS/KiSS1R system and its functional role in rabbit corpora lutea (CL) at days 4 (early-), 9 (mid-), and 13 (late-stage) of pseudopregnancy. In vitro progesterone, prostaglandin (PG) F2α (PGF2α) and E2 (PGE2) productions and prostaglandin-endoperoxide synthase 1 (PTGS1) and 2 (PTGS2) activities were evaluated. Immune reactivity (IR) for KiSS and KiSS1R were detected in luteal cells at nuclear and cytoplasmic level at all luteal stage for KiSS and only at early- and mid-stage for KiSS1R; IR decreased from early- to later stages of pseudopregnancy. The KiSS-10 augmented progesterone and PGE2 and diminished PGF2α secretions by early- and mid-CL; KiSS-10 reduced PTGS2 activity at early- and mid-stages, but did not affect PTGS1 at any luteal stages. The antagonist KiSS-234 counteracted all KiSS-10 effects. This study shows that the KiSS/KiSS1R system is expressed in CL of pseudopregnant rabbits and exerts a luteotropic action by down-regulating PTGS2, which decreases PGF2α and increases PGE2 and progesterone.
Diversity and Disparity of Therocephalia: Macroevolutionary Patterns through Two Mass Extinctions
Authors: Grunert Henrik Richard , Brocklehurst Neil , Fröbisch Jörg 
Published: March 2019

AbstractMass extinctions have the potential to substantially alter the evolutionary trends in a clade. If new regions of ecospace are made available, the clade may radiate. If, on the other hand, the clade passes through an evolutionary “bottleneck” by substantially reducing its species richness, then subsequent radiations may be restricted in the disparity they attain. Here we compare the patterns of diversity and disparity in the Therocephalia, a diverse lineage of amniotes that survived two mass extinction events. We use time calibrated phylogeny and discrete character data to assess macroevolutionary patterns. The two are coupled through the early history of therocephalians, including a radiation following the late Guadalupian extinction. Diversity becomes decoupled from disparity across the end-Permian mass extinction. The number of species decreases throughout the Early Triassic and never recovers. However, while disparity briefly decreases across the extinction boundary, it recovers and remains high until the Middle Triassic.
Identifying progressive CKD from healthy population using Bayesian network and artificial intelligence: A worksite-based cohort study
Authors: Kanda Eiichiro , Kanno Yoshihiko , Katsukawa Fuminori 
Published: March 2019

AbstractIdentifying progressive early chronic kidney disease (CKD) patients at a health checkup is a good opportunity to improve their prognosis. However, it is difficult to identify them using common health tests. This worksite-based cohort study for 7 years in Japan (n = 7465) was conducted to evaluate the progression of CKD. The outcome was aggravation of the KDIGO prognostic category of CKD 7 years later. The subjects were male, 59.1%; age, 50.1 ± 6.3 years; and eGFR, 79 ± 14.4 mL/min/1.73 m2. The number of subjects showing CKD progression started to increase from 3 years later. Vector analysis showed that CKD stage G1 A1 was more progressive than CKD stage G2 A1. Bayesian networks showed that the time-series changes in the prognostic category of CKD were related to the outcome. Support vector machines including time-series data of the prognostic category of CKD from 3 years later detected the high possibility of the outcome not only in subjects at very high risks but also in those at low risks at baseline. In conclusion, after the evaluation of kidney function at a health checkup, it is necessary to follow up not only patients at high risks but also patients at low risks at baseline for 3 years and longer.
Tasselseed5 overexpresses a wound-inducible enzyme, ZmCYP94B1, that affects jasmonate catabolism, sex determination, and plant architecture in maize
Authors: Lunde China , Kimberlin Athen , Leiboff Samuel , Koo Abraham J. , Hake Sarah 
Published: March 2019

AbstractMaize is monecious, with separate male and female inflorescences. Maize flowers are initially bisexual but achieve separate sexual identities through organ arrest. Loss-of-function mutants in the jasmonic acid (JA) pathway have only female flowers due to failure to abort silks in the tassel. Tasselseed5 (Ts5) shares this phenotype but is dominant. Positional cloning and transcriptomics of tassels identified an ectopically expressed gene in the CYP94B subfamily, Ts5 (ZmCYP94B1). CYP94B enzymes are wound inducible and inactivate bioactive jasmonoyl-L-isoleucine (JA-Ile). Consistent with this result, tassels and wounded leaves of Ts5 mutants displayed lower JA and JA-lle precursors and higher 12OH-JA-lle product than the wild type. Furthermore, many wounding and jasmonate pathway genes were differentially expressed in Ts5 tassels. We propose that the Ts5 phenotype results from the interruption of JA signaling during sexual differentiation via the upregulation of ZmCYP94B1 and that its proper expression maintains maize monoecy.
Calcium–calmodulin gating of a pH-insensitive isoform of connexin43 gap junctions
Authors: Wei Siyu , Cassara Christian , Lin Xianming , Veenstra Richard D. 
Published: March 2019

Abstract
Intracellular protons and calcium ions are two major chemical factors that regulate connexin43 (Cx43) gap junction communication and the synergism or antagonism between pH and Ca2+ has been questioned for decades. To assess the ability of Ca2+ ions to modulate Cx43 junctional conductance (gj) in the absence of pH-sensitivity, patch clamp experiments were performed on Neuroblastoma-2a (N2a) cells or neonatal mouse ventricular myocytes (NMVMs) expressing either full-length Cx43 or the Cx43-M257 (Cx43K258stop) mutant protein, a carboxyl-terminus (CT) truncated version of Cx43 lacking pH-sensitivity. The addition of 1 μM ionomycin to normal calcium saline reduced Cx43 or Cx43-M257 gj to zero within 15 min of perfusion. This response was prevented by Ca2+-free saline or addition of 100 nM calmodulin (CaM) inhibitory peptide to the internal pipette solution. Internal addition of a connexin50 cytoplasmic loop calmodulin-binding domain (CaMBD) mimetic peptide (200 nM) prevented the Ca2+/ionomycin-induced decrease in Cx43 gj, while 100 μM Gap19 peptide had minimal effect. The investigation of the transjunctional voltage (Vj) gating properties of NMVM Cx43-M257 gap junctions confirmed the loss of the fast inactivation of Cx43-M257 gj, but also noted the abolishment of the previously reported facilitated recovery of gj from inactivating potentials. We conclude that the distal CT domain of Cx43 contributes to the Vj-dependent fast inactivation and facilitated recovery of Cx43 gap junctions, but the Ca2+/CaM-dependent gating mechanism remains intact in its absence. Sequence-specific connexin CaMBD mimetic peptides act by binding Ca2+/CaM non-specifically and the Cx43 mimetic Gap19 peptide has negligible effect on this chemical gating mechanism.
Reversing resistance to counter antimicrobial resistance in the World Health Organisation’s critical priority of most dangerous pathogens
Authors: Venter Henrietta 
Published: March 2019

Abstract
The speed at which bacteria develop antimicrobial resistance far outpace drug discovery and development efforts resulting in untreatable infections. The World Health Organisation recently released a list of pathogens in urgent need for the development of new antimicrobials. The organisms that are listed as the most critical priority are all Gram-negative bacteria resistant to the carbapenem class of antibiotics. Carbapenem resistance in these organisms is typified by intrinsic resistance due to the expression of antibiotic efflux pumps and the permeability barrier presented by the outer membrane, as well as by acquired resistance due to the acquisition of enzymes able to degrade β-lactam antibiotics. In this perspective article we argue the case for reversing resistance by targeting these resistance mechanisms – to increase our arsenal of available antibiotics and drastically reduce antibiotic discovery times – as the most effective way to combat antimicrobial resistance in these high priority pathogens.