bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Complex Interplay of Anionic Phospholipid Binding Regulates 3′-Phosphoinositide-Dependent-Kinase-1 Homodimer Activation
Authors: Heras-Martínez Gloria de las , Calleja Véronique , Bailly Remy , Dessolin Jean , Larijani Banafshé , Requejo-Isidro Jose 
Published: October 2019

Abstract3′-Phosphoinositide-dependent-Kinase-1 (PDK1) is a master regulator whereby its PI3-kinase-dependent dysregulation in human pathologies is well documented. Understanding the direct role for PtdIns(3,4,5)P3 and other anionic phospholipids in the regulation of PDK1 conformational dynamics and its downstream activation remains incomplete. Using advanced quantitative-time-resolved imaging (Fluorescence Lifetime Imaging and Fluorescence Correlation Spectroscopy) and molecular modelling, we show an interplay of antagonistic binding effects of PtdIns(3,4,5)P3 and other anionic phospholipids, regulating activated PDK1 homodimers. We demonstrate that phosphatidylserine maintains PDK1 in an inactive conformation. The dysregulation of the PI3K pathway affects the spatio-temporal and conformational dynamics of PDK1 and the activation of its downstream substrates. We have established a new anionic-phospholipid-dependent model for PDK1 regulation, depicting the conformational dynamics of multiple homodimer states. We show that the dysregulation of the PI3K pathway perturbs equilibrium between the PDK1 homodimer conformations. Our findings provide a role for the PtdSer binding site and its previously unrewarding role in PDK1 downregulation, suggesting a possible therapeutic strategy where the constitutively active dimer conformer of PDK1 may be rendered inactive by small molecules that drive it to its PtdSer-bound conformer.
Reporter lines based on the gexp02 promoter enable early quantification of sexual conversion rates in the malaria parasite Plasmodium falciparum
Authors: Portugaliza Harvie P. , Llorà-Batlle Oriol , Rosanas-Urgell Anna , Cortés Alfred 
Published: October 2019

AbstractTransmission of malaria parasites from humans to mosquito vectors requires that some asexual parasites differentiate into sexual forms termed gametocytes. The balance between proliferation in the same host and conversion into transmission forms can be altered by the conditions of the environment. The ability to accurately measure the rate of sexual conversion under different conditions is essential for research addressing the mechanisms underlying sexual conversion, and to assess the impact of environmental factors. Here we describe new Plasmodium falciparum transgenic lines with genome-integrated constructs in which a fluorescent reporter is expressed under the control of the promoter of the gexp02 gene. Using these parasite lines, we developed a sexual conversion assay that shortens considerably the time needed for an accurate determination of sexual conversion rates, and dispenses the need to add chemicals to inhibit parasite replication. Furthermore, we demonstrate that gexp02 is expressed specifically in sexual parasites, with expression starting as early as the sexual ring stage, which makes it a candidate marker for circulating sexual rings in epidemiological studies.
Hearing impairment and associated morphological changes in pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice
Authors: Fulop Daniel Balazs , Humli Viktoria , Szepesy Judit , Ott Virag , Reglodi Dora , Gaszner Balazs , Nemeth Adrienn , Szirmai Agnes , Tamas Laszlo , Hashimoto Hitoshi , Zelles Tibor , Tamas Andrea 
Published: October 2019

AbstractPituitary adenylate cyclase activating polypeptide (PACAP) is a regulatory and cytoprotective neuropeptide, its deficiency implies accelerated aging in mice. It is present in the auditory system having antiapoptotic effects. Expression of Ca2+-binding proteins and its PAC1 receptor differs in the inner ear of PACAP-deficient (KO) and wild-type (WT) mice. Our aim was to elucidate the functional role of PACAP in the auditory system. Auditory brainstem response (ABR) tests found higher hearing thresholds in KO mice at click and low frequency burst stimuli. Hearing impairment at higher frequencies showed as reduced ABR wave amplitudes and latencies in KO animals. Increase in neuronal activity, demonstrated by c-Fos immunolabeling, was lower in KO mice after noise exposure in the ventral and dorsal cochlear nuclei. Noise induced neuronal activation was similar in further relay nuclei of the auditory pathway of WT and KO mice. Based on the similar inflammatory and angiogenic protein profile data from cochlear duct lysates, neither inflammation nor disturbed angiogenesis, as potential pathological components in sensorineural hearing losses, seem to be involved in the pathomechanism of the presented functional and morphological changes in PACAP KO mice. The hearing impairment is probably concomitant with the markedly accelerated aging processes in these animals.
Inhibition of dicer activity in lepidopteran and dipteran cells by baculovirus-mediated expression of Flock House virus B2
Authors: Hodgson Jeffrey J. , Wenger Luke W. , Clem Rollie J. , Passarelli A. Lorena 
Published: October 2019

AbstractPrior studies have suggested that insect DNA viruses are negatively affected by dicer-2-mediated RNA interference (RNAi). To examine this further, we utilized an in vitro assay to measure dicer activity in lepidopteran and dipteran cells, combined with baculoviruses expressing the RNAi suppressor B2 from Flock House virus or Aedes aegypti dicer-2 (Aedicer-2) using a constitutive heat shock promoter. Addition of cell lysates containing baculovirus-expressed B2 to lysates from dipteran (S2, Aag2) or lepidopteran (Sf9) cells inhibited endogenous dicer activity in a dose-dependent manner, while expression of Aedicer-2 restored siRNA production in Ae. albopictus C6/36 cells, which are dicer-2 defective. However, B2 expression from the constitutive heat shock promoter had no impact on baculovirus replication or virulence in cell lines or larvae that were either highly permissive (Trichoplusia ni) or less susceptible (Spodoptera frugiperda) to infection. We determined that this constitutive level of B2 expression had little to no ability to suppress dicer activity in cell lysates, but higher expression of B2, following heat shock treatment, inhibited dicer activity in all cells tested. Thus, we cannot rule out the possibility that optimized expression of B2 or other RNAi suppressors may increase baculovirus replication and expression of heterologous proteins by baculoviruses.
Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
Authors: Cundiff Mary D. , Hurley Christina M. , Wong Jeremy D. , Boscia Joseph A. , Bashyal Aarti , Rosenberg Jake , Reichard Eden L. , Nassif Nicholas D. , Brodbelt Jennifer S. , Kraut Daniel A. 
Published: October 2019

AbstractThe ubiquitin-proteasome system (UPS) is responsible for the bulk of protein degradation in eukaryotic cells, but the factors that cause different substrates to be unfolded and degraded to different extents are still poorly understood. We previously showed that polyubiquitinated substrates were degraded with greater processivity (with a higher tendency to be unfolded and degraded than released) than ubiquitin-independent substrates. Thus, even though ubiquitin chains are removed before unfolding and degradation occur, they affect the unfolding of a protein domain. How do ubiquitin chains activate the proteasome’s unfolding ability? We investigated the roles of the three intrinsic proteasomal ubiquitin receptors - Rpn1, Rpn10 and Rpn13 - in this activation. We find that these receptors are required for substrate-mediated activation of the proteasome’s unfolding ability. Rpn13 plays the largest role, but there is also partial redundancy between receptors. The architecture of substrate ubiquitination determines which receptors are needed for maximal unfolding ability, and, in some cases, simultaneous engagement of ubiquitin by multiple receptors may be required. Our results suggest physical models for how ubiquitin receptors communicate with the proteasomal motor proteins.
High susceptibility, viral dynamics and persistence of South American Zika virus in New World monkey species
Authors: Berry Neil , Ferguson Deborah , Ham Claire , Hall Jo , Jenkins Adrian , Giles Elaine , Devshi Dhruti , Kempster Sarah , Rose Nicola , Dowall Stuart , Fritzsche Martin , Bleazard Thomas , Hewson Roger , Almond Neil 
Published: October 2019

AbstractSouth American Zika virus (ZIKV) recently emerged as a novel human pathogen, linked with neurological disorders. However, comparative ZIKV infectivity studies in New World primates are lacking. Two members of the Callitrichidae family, common marmosets (Callithrix jacchus) and red-bellied tamarins (Saguinus labiatus), were highly susceptible to sub-cutaneous challenge with the Puerto Rico-origin ZIKVPRVABC59 strain. Both exhibited rapid, high, acute viraemia with early neuroinvasion (3 days) in peripheral and central nervous tissue. ZIKV RNA levels in blood and tissues were significantly higher in New World hosts compared to Old World species (Macaca mulatta, Macaca fascicularis). Tamarins and rhesus macaques exhibited loss of zonal occludens-1 (ZO-1) staining, indicative of a compromised blood-brain barrier 3 days post-ZIKV exposure. Early, widespread dissemination across multiple anatomical sites distant to the inoculation site preceded extensive ZIKV persistence after 100 days in New and Old World lineages, especially lymphoid, neurological and reproductive sites. Prolonged persistence in brain tissue has implications for otherwise resolved human ZIKV infection. High susceptibility of distinct New World species underscores possible establishment of ZIKV sylvatic cycles in primates indigenous to ZIKV endemic regions. Tamarins and marmosets represent viable New World models for ZIKV pathogenesis and therapeutic intervention studies, including vaccines, with contemporary strains.
Pomegranate Juice and Extract Consumption Increases the Resistance to UVB-induced Erythema and Changes the Skin Microbiome in Healthy Women: a Randomized Controlled Trial
Authors: Henning Susanne M. , Yang Jieping , Lee Ru-Po , Huang Jianjun , Hsu Mark , Thames Gail , Gilbuena Irene , Long Jianfeng , Xu Yunhui , Park Esther HaeIn , Tseng Chi-Hong , Kim Jenny , Heber David , Li Zhaoping 
Published: October 2019

AbstractIn vitro and animal studies have demonstrated that topical application and oral consumption of pomegranate reduces UVB-induced skin damage. We therefore investigated if oral pomegranate consumption will reduce photodamage from UVB irradiation and alter the composition of the skin microbiota in a randomized controlled, parallel, three-arm, open label study. Seventy-four female participants (30–45 years) with Fitzpatrick skin type II-IV were randomly assigned (1:1:1) to 1000 mg of pomegranate extract (PomX), 8 oz of pomegranate juice (PomJ) or placebo for 12 weeks. Minimal erythema dose (MED) and melanin index were determined using a cutometer (mexameter probe). Skin microbiota was determined using 16S rRNA sequencing. The MED was significantly increased in the PomX and PomJ group compared to placebo. There was no significant difference on phylum, but on family and genus level bacterial composition of skin samples collected at baseline and after 12 week intervention showed significant differences between PomJ, PomX and placebo. Members of the Methylobacteriaceae family contain pigments absorbing UV irradiation and might contribute to UVB skin protection. However, we were not able to establish a direct correlation between increased MED and bacterial abundance. In summary daily oral pomegranate consumption may lead to enhanced protection from UV photodamage.
On-chip Fourier-transform spectrometer based on spatial heterodyning tuned by thermo-optic effect
Authors: Montesinos-Ballester Miguel , Liu Qiankun , Vakarin Vladyslav , Ramirez Joan Manel , Alonso-Ramos Carlos , Roux Xavier Le , Frigerio Jacopo , Ballabio Andrea , Talamas Enrico , Vivien Laurent , Isella Giovanni , Marris-Morini Delphine 
Published: October 2019

AbstractMiniaturized optical spectrometers providing broadband operation and fine resolution have an immense potential for applications in remote sensing, non-invasive medical diagnostics and astronomy. Indeed, optical spectrometers working in the mid-infrared spectral range have garnered a great interest for their singular capability to monitor the main absorption fingerprints of a wide range of chemical and biological substances. Fourier-transform spectrometers (FTS) are a particularly interesting solution for the on-chip integration due to their superior robustness against fabrication imperfections. However, the performance of current on-chip FTS implementations is limited by tradeoffs in bandwidth and resolution. Here, we propose a new FTS approach that gathers the advantages of spatial heterodyning and optical path tuning by thermo-optic effect to overcome this tradeoff. The high resolution is provided by spatial multiplexing among different interferometers with increasing imbalance length, while the broadband operation is enabled by fine tuning of the optical path delay in each interferometer harnessing the thermo-optic effect. Capitalizing on this concept, we experimentally demonstrate a mid-infrared SiGe FTS, with a resolution better than 15 cm−1 and a bandwidth of 603 cm−1 near 7.7 μm wavelength with a 10 MZI array. This is a resolution comparable to state-of-the-art on-chip mid-infrared spectrometers with a 4-fold bandwidth increase with a footprint divided by a factor two.
Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion
Authors: Bhuvanendran Saatheeyavaane , Bakar Siti Najmi Syuhadaa , Kumari Yatinesh , Othman Iekhsan , Shaikh Mohd. Farooq , Hassan Zurina 
Published: October 2019

AbstractAlzheimer’s disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.
Analysis of CT morphologic features and attenuation for differentiating among transient lesions, atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive and invasive adenocarcinoma presenting as pure ground-glass nodules
Authors: Qi Lin , Xue Ke , Li Cheng , He Wenjie , Mao Dingbiao , Xiao Li , Hua Yanqing , Li Ming 
Published: October 2019

AbstractThin-section computed tomography (TSCT) imaging biomarkers are uncertain to distinguish progressive adenocarcinoma from benign lesions in pGGNs. The purpose of this study was to evaluate the usefulness of TSCT characteristics for differentiating among transient (TRA) lesions, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) presenting as pure ground-glass nodules (pGGNs). Between January 2016 and January 2018, 255 pGGNs, including 64 TRA, 22 AAH, 37 AIS, 108 MIA and 24 IAC cases, were reviewed on TSCT images. Differences in TSCT characteristics were compared among these five subtypes of pGGNs. Logistic analysis was performed to identify significant factors for predicting MIA and IAC. Progressive pGGNs were more likely to be round or oval in shape, with clear margins, air bronchograms, vascular and pleural changes, creep growth, and bubble-like lucency than were non-progressive pGGNs. The optimal cut-off values of the maximum diameter for differentiating non-progressive from progressive pGGNs and IAC from non-IAC were 6.5 mm and 11.5 mm, respectively. For the prediction of IAC vs. non-IAC and non-progressive vs. progressive adenocarcinoma, the areas under the receiver operating characteristics curves were 0.865 and 0.783 for maximum diameter and 0.784 and 0.722 for maximum CT attenuation, respectively. The optimal cut-off values of maximum CT attenuation were −532 HU and −574 HU for differentiating non-progressive from progressive pGGNs and IAC from non-IAC, respectively. Maximum diameter, maximum attenuation and morphological characteristics could help distinguish TRA lesions from MIA and IAC but not from AAH. So, CT morphologic characteristics, diameter and attenuation parameters are useful for differentiating among pGGNs of different subtypes.
Methylation of guar gum for improving mechanical and barrier properties of biodegradable packaging films
Authors: Tripathi Jyoti , Ambolikar Rupali , Gupta Sumit , Jain Dheeraj , Bahadur Jitendra , Variyar Prasad Shekhar 
Published: October 2019

AbstractImproving functional properties of biopolymers for use as environment friendly packaging is an area of current interest. Biodegradable films with improved barrier and mechanical properties were prepared from methylated guar gum. Methylation resulted in structural modification of guar gum (GG) promoting greater crystallization thereby enhancing thermal stability towards decomposition. Reduction in radius of gyration (Rg), weight average molecular weight (Mw), and an increase in polydispersity index (PDI) were also observed due to methylation. Methylated guar gum (MGG) films exhibited 40% lower water vapor transmission rate (WVTR) as compared to control purified guar gum (PGG) films. Films prepared by partial replacement of PGG with MGG (10, 25, 50, 75 and 100% w/w) showed gradual improvement in percent elongation. The study gives an insight on the role of methylation in enhancing barrier and mechanical properties of GG based biodegradable films for possible application in food packaging.
Growth and single cell kinetics of the loricate choanoflagellate Diaphanoeca grandis
Authors: Eriksen Niels Thomas , Tophøj Jakob , Wollenberg Rasmus Dam , Sondergaard Teis Esben , Funch Peter , Andersen Per 
Published: October 2019

AbstractChoanoflagellates are common members of planktonic communities. Some have complex life histories that involve transitions between multiple cell stages. We have grown the loricate choanoflagellate Diaphanoeca grandis on the bacterium Pantoea sp. and integrated kinetic observations at the culture level and at the single cell level. The life history of D. grandis includes a cell division cycle with a number of recognisable cell stages. Mature, loricate D. grandis were immobile and settled on the bottom substratum. Daughter cells were ejected from the lorica 30 min. after cell division, became motile and glided on the bottom substratum until they assembled a lorica. Single cell kinetics could explain overall growth kinetics in D. grandis cultures. The specific growth rate was 0.72 day−1 during exponential growth while mature D. grandis produced daughter cells at a rate of 0.9 day−1. Daughter cells took about 1.2 h to mature. D. grandis was able to abandon and replace its lorica, an event that delayed daughter cell formation by more than 2 days. The frequency of daughter cell formation varied considerably among individuals and single cell kinetics demonstrated an extensive degree of heterogeneity in D. grandis cultures, also when growth appeared to be balanced.
Crash dynamics of interdependent networks
Authors: Li Jie , Xia Chengyi , Xiao Gaoxi , Moreno Yamir 
Published: October 2019

AbstractThe emergence and evolution of real-world systems have been extensively studied in the last few years. However, equally important phenomena are related to the dynamics of systems’ collapse, which has been less explored, especially when they can be cast into interdependent systems. In this paper, we develop a dynamical model that allows scrutinizing the collapse of systems composed of two interdependent networks. Specifically, we explore the dynamics of the system’s collapse under two scenarios: in the first one, the condition for failure should be satisfied for the focal node as well as for its corresponding node in the other network; while in the second one, it is enough that failure of one of the nodes occurs in either of the two networks. We report extensive numerical simulations of the dynamics performed in different setups of interdependent networks, and analyze how the system behavior depends on the previous scenarios as well as on the topology of the interdependent system. Our results can provide valuable insights into the crashing dynamics and evolutionary properties of interdependent complex systems.
SPIONs/3D SiSBA-16 based Multifunctional Nanoformulation for target specific cisplatin release in colon and cervical cancer cell lines
Authors: Jermy B. Rabindran , Alomari Munther , Ravinayagam Vijaya , Almofty Sarah Ameen , Akhtar Sultan , Borgio J. Francis , AbdulAzeez Sayed 
Published: October 2019

AbstractMultifunctional nanomaterials can be used for dual applications: drug delivery as well as in bioimaging. In current study, we investigated potential use of silica based supports; 3D cage type SiSBA-16 (S-16), monodispersed hydrophilic spherical silica (HYPS) and mesocellular foam (MSU-F) for cisplatin (Cp) delivery. To obtain magnetic resonance characteristics, 10 wt% iron oxide was loaded through enforced adsorption technique. For pH stimuli responsive release of Cp, 10 wt%SPIONs/S-16 was functionalized with 3-(Aminopropyl)triethoxysilane (A) and poly acrylic acid (PAA) termed as 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp. By TEM analysis, the average diameter of the SPIONs was found to range between 10–60 nm. VSM analysis showed saturation magnetization over S-16, HYPS and MSU-F were in the following order: 10 wt%SPIONs/HYPS (4.08 emug−1) > 10 wt%SPIONs /S-16 (2.39 emug−1) > 10 wt%SPIONs/MSU-F (0.23 emug−1). Cp release study using dialysis membrane in PBS solution over 10 wt%SPIONs/S-16 nanoformulations showed highest cumulative release (65%) than 10 wt%SPIONs/MSU-F-A-Cp (63%), 10 wt%SPIONs/HYPS-A-Cp (58%), and Cp-F127/S-16 (53%), respectively. 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp were evaluated for in vitro target anticancer efficiency in human cancer cell lines (colon cancer (HCT 116), cervical cancer (HeLa)) and normal cells (Human embryonic kidney cells (HEK293) using MTT and DAPI staining. 10 wt%SPIONs/S-16-A-Cp treated Hela and HCT116 cancerous cell lines showed significant control of cell growth, apoptotic activity and less cytotoxic effect as compared to Cp and 10 wt%SPIONs/S-16. Target specific Cp release in the cells shows that 10 wt%SPIONs/S-16-A-Cp can be easily upgraded for magnetic resonance imaging capability.