bluuebunny/crossref_metadata_2025_split huggingface dataset:
The unique structural features of carbonmonoxy hemoglobin from the sub-Antarctic fish Eleginops maclovinus
Authors: Balasco Nicole , Vitagliano Luigi , Merlino Antonello , Verde Cinzia , Mazzarella Lelio , Vergara Alessandro 
Published: December 2019

AbstractTetrameric hemoglobins (Hbs) are prototypical systems for the investigations of fundamental properties of proteins. Although the structure of these proteins has been known for nearly sixty years, there are many aspects related to their function/structure that are still obscure. Here, we report the crystal structure of a carbonmonoxy form of the Hb isolated from the sub-Antarctic notothenioid fish Eleginops maclovinus characterised by either rare or unique features. In particular, the distal site of the α chain results to be very unusual since the distal His is displaced from its canonical position. This displacement is coupled with a shortening of the highly conserved E helix and the formation of novel interactions at tertiary structure level. Interestingly, the quaternary structure is closer to the T-deoxy state of Hbs than to the R-state despite the full coordination of all chains. Notably, these peculiar structural features provide a rationale for some spectroscopic properties exhibited by the protein in solution. Finally, this unexpected structural plasticity of the heme distal side has been associated with specific sequence signatures of various Hbs.
Course of depressive symptoms in men and women: differential effects of social, psychological, behavioral and somatic predictors
Authors: Tibubos Ana N. , Brähler Elmar , Ernst Mareike , Baumgarten Carlotta , Wiltink Joerg , Burghardt Juliane , Michal Matthias , Ghaemi Kerahrodi Jasmin , Schulz Andreas , Wild Philipp S. , Münzel Thomas , Schmidtmann Irene , Lackner Karl J. , Pfeiffer Norbert , Borta Andreas , Beutel Manfred E. 
Published: December 2019

AbstractIn this study, we aimed to identify the most important and sex-specific social, psychological, behavioral and somatic predictors of recurrent depressive symptoms. Data was obtained at two measurement points within five years by the Gutenberg Health Study (GHS). Out of N = 12,061 individuals, a sample of 877 (age 52.3 ± 9.9) who reported clinically relevant depressive symptoms at baseline was analyzed. Univariate analyses and multiple logistic regression analyses were conducted. Almost half of participants depressed at baseline also reported depressive symptoms five years later. Sex-stratified multivariate analyses revealed that solely social support remained a significant protective predictor against recurrence of depression in men (OR = 0.93; CI95% = 0.87–0.99), whereas in women smoking (OR = 1.97; CI95% = 1.23–3.22), and Type D personality (OR = 1.65; CI95% = 1.10–2.49) were significant risk factors. However, when analyzing the entire sample, no interaction effect between sex and each predictor turned out to be significant. Only social support was retained as an overall predictive factor. As depressive symptoms recur, depressive vulnerability is established involving personality, health behavior and social factors. Although no significant sex-specific interactions were observed, sex-stratified analyses point out different patterns for relevant predictors of recurrent depressive symptoms in men and women.
3β, 6β-dichloro-5-hydroxy-5α-cholestane facilitates neuronal development through modulating TrkA signaling regulated proteins in primary hippocampal neuron
Authors: Hannan Md. Abdul , Haque Md. Nazmul , Dash Raju , Alam Mahboob , Moon Il Soo 
Published: December 2019

AbstractPotentiating neuritogenesis through pharmacological intervention might hold therapeutic promise in neurodegenerative disorders and acute brain injury. Here, we investigated the novel neuritogenic potentials of a steroidal chlorohydrin, 3β, 6β-dichloro-5-hydroxy-5α-cholestane (hereafter, SCH) and the change in cellular proteome to gain insight into the underlying mechanism of its neurotrophic activity in hippocampal neurons. Morphometric analysis showed that SCH promoted early neuronal differentiation, dendritic arborization and axonal maturation. Proteomic and bioinformatic analysis revealed that SCH induced upregulation of several proteins, including those associated with neuronal differentiation and development. Immunocytochemical data further indicates that SCH-treated neurons showed upregulation of Hnrnpa2b1 and Map1b, validating their proteomic profiles. In addition, a protein-protein interaction network analysis identified TrkA as a potential target connecting most of the upregulated proteins. The neurite outgrowth effect of SCH was suppressed by TrkA inhibitor, GW441756, verifying TrkA-dependent activity of SCH, which further supports the connection of TrkA with the upregulated proteins. Also, the computational analysis revealed that SCH interacts with the NGF-binding domain of TrkA through Phe327 and Asn355. Collectively, our findings provide evidence that SCH promotes neuronal development via upregulating TrkA-signaling proteins and suggest that SCH could be a promising therapeutic agent in the prevention and treatment of neurodegenerative disorders.
Identification of a Phenylthiazole Small Molecule with Dual Antifungal and Antibiofilm Activity Against Candida albicans and Candida auris
Authors: Mohammad Haroon , Eldesouky Hassan E. , Hazbun Tony , Mayhoub Abdelrahman S. , Seleem Mohamed N. 
Published: December 2019

AbstractCandida species are a leading source of healthcare infections globally. The limited number of antifungal drugs combined with the isolation of Candida species, namely C. albicans and C. auris, exhibiting resistance to current antifungals necessitates the development of new therapeutics. The present study tested 85 synthetic phenylthiazole small molecules for antifungal activity against drug-resistant C. albicans. Compound 1 emerged as the most potent molecule, inhibiting growth of C. albicans and C. auris strains at concentrations ranging from 0.25–2 µg/mL. Additionally, compound 1 inhibited growth of other clinically-relevant yeast (Cryptococcus) and molds (Aspergillus) at a concentration as low as 0.50 µg/mL. Compound 1 exhibited rapid fungicidal activity, reducing the burden of C. albicans and C. auris below the limit of detection within 30 minutes. Compound 1 exhibited potent antibiofilm activity, similar to amphotericin B, reducing the metabolic activity of adherent C. albicans and C. auris biofilms by more than 66% and 50%, respectively. Furthermore, compound 1 prolonged survival of Caenorhabditis elegans infected with strains of C. albicans and C. auris, relative to the untreated control. The present study highlights phenylthiazole small molecules, such as compound 1, warrant further investigation as novel antifungal agents for drug-resistant Candida infections.
Epigenetic deregulation of GATA3 in neuroblastoma is associated with increased GATA3 protein expression and with poor outcomes
Authors: Almutairi Bader , Charlet Jessica , Dallosso Anthony R. , Szemes Marianna , Etchevers Heather C. , Malik Karim T. A. , Brown Keith W. 
Published: December 2019

AbstractTo discover epigenetic changes that may underly neuroblastoma pathogenesis, we identified differentially methylated genes in neuroblastoma cells compared to neural crest cells, the presumptive precursors cells for neuroblastoma, by using genome-wide DNA methylation analysis. We previously described genes that were hypermethylated in neuroblastoma; in this paper we report on 67 hypomethylated genes, which were filtered to select genes that showed transcriptional over-expression and an association with poor prognosis in neuroblastoma, highlighting GATA3 for detailed studies. Specific methylation assays confirmed the hypomethylation of GATA3 in neuroblastoma, which correlated with high expression at both the RNA and protein level. Demethylation with azacytidine in cultured sympathetic ganglia cells led to increased GATA3 expression, suggesting a mechanistic link between GATA3 expression and DNA methylation. Neuroblastomas that had completely absent GATA3 methylation and/or very high levels of protein expression, were associated with poor prognosis. Knock-down of GATA3 in neuroblastoma cells lines inhibited cell proliferation and increased apoptosis but had no effect on cellular differentiation. These results identify GATA3 as an epigenetically regulated component of the neuroblastoma transcriptional control network, that is essential for neuroblastoma proliferation. This suggests that the GATA3 transcriptional network is a promising target for novel neuroblastoma therapies.
Evolutionary conservation of the intrinsic disorder-based Radical-Induced Cell Death1 hub interactome
Authors: Christensen Lise Friis , Staby Lasse , Bugge Katrine , O’Shea Charlotte , Kragelund Birthe B. , Skriver Karen 
Published: December 2019

AbstractRadical-Induced Cell Death1 (RCD1) functions as a cellular hub interacting with intrinsically disordered transcription factor regions, which lack a well-defined three-dimensional structure, to regulate plant stress. Here, we address the molecular evolution of the RCD1-interactome. Using bioinformatics, its history was traced back more than 480 million years to the emergence of land plants with the RCD1-binding short linear motif (SLiM) identified from mosses to flowering plants. SLiM variants were biophysically verified to be functional and to depend on the same RCD1 residues as the DREB2A transcription factor. Based on this, numerous additional members may be assigned to the RCD1-interactome. Conservation was further strengthened by similar intrinsic disorder profiles of the transcription factor homologs. The unique structural plasticity of the RCD1-interactome, with RCD1-binding induced α-helix formation in DREB2A, but not detectable in ANAC046 or ANAC013, is apparently conserved. Thermodynamic analysis also indicated conservation with interchangeability between Arabidopsis and soybean RCD1 and DREB2A, although with fine-tuned co-evolved binding interfaces. Interruption of conservation was observed, as moss DREB2 lacked the SLiM, likely reflecting differences in plant stress responses. This whole-interactome study uncovers principles of the evolution of SLiM:hub-interactions, such as conservation of α-helix propensities, which may be paradigmatic for disorder-based interactomes in eukaryotes.
Ultrasound-induced Cavitation enhances the efficacy of Chemotherapy in a 3D Model of Pancreatic Ductal Adenocarcinoma with its microenvironment
Authors: Leenhardt R. , Camus M. , Mestas J. L. , Jeljeli M. , Abou Ali E. , Chouzenoux S. , Bordacahar B. , Nicco C. , Batteux F. , Lafon C. , Prat F. 
Published: December 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) is supported by a complex microenvironment whose physical contribution to chemoresistance could be overcome by ultrasound (US) therapy. This study aims to investigate the ability of US-induced inertial cavitation in association with chemotherapy to alter tumor cell viability via microenvironment disruption. For this purpose, we used a 3D-coculture PDAC model partially mimicking the tumor and its microenvironment. Coculture spheroids combining DT66066 cells isolated from KPC-transgenic mice and murine embryonic fibroblasts (iMEF) were obtained by using a magnetic nanoshuttle method. Spheroids were exposed to US with incremental inertial cavitation indexes. Conditions studied included control, gemcitabine, US-cavitation and US-cavitation + gemcitabine. Spheroid viability was assessed by the reduction of resazurin and flow cytometry. The 3D-coculture spheroid model incorporated activated fibroblasts and produced type 1-collagen, thus providing a partial miniature representation of tumors with their microenvironment. Main findings were: (a) Gemcitabine (5 μM) was significantly less cytotoxic in the presence of KPC/iMEFs spheroids compared with KPC (fibroblast-free) spheroids; (b) US-induced inertial cavitation combined with Gemcitabine significantly decreased spheroid viability compared to Gemcitabine alone; (c) both cavitation and chemotherapy affected KPC cell viability but not that of fibroblasts, confirming the protective role of the latter vis-à-vis tumor cells. Gemcitabine toxicity is enhanced when cocultured spheroids of KPC and iMEF are exposed to US-cavitation. Although the model used is only a partial representation of PDAC, this experience supports the hypothesis that US-inertial cavitation can enhance drug penetration and cytotoxicity by disrupting PDAC microenvironment.
Damages caused by hurricane Irma in the human-degraded mangroves of Saint Martin (Caribbean)
Authors: Walcker R. , Laplanche C. , Herteman M. , Lambs L. , Fromard F. 
Published: December 2019

AbstractIn early September 2017, Irma was the most powerful hurricane that struck the northern Caribbean over the last 100 years. In the 21st century, the stronger types of tropical cyclones will likely increase in frequency due to the climate change and internal climate variability. Lessons to anticipate the response of mangroves to this intensification can be learned from this extreme event. Here, we analysed damages caused in mangrove forests of the Saint Martin Island. Mangroves of this island were previously degraded due to historic human pressures and recent over-urbanisation. Forest inventories and time series of very high resolution satellite images revealed that approximately 80% of the mangrove area was damaged by the hurricane. Results highlighted distinct rates of forest recovery. Early and rapid recoveries were largely observed in most study sites. However, some mangroves were still unable to recover fourteen months after the disturbance. The human-induced degradation of the ecosystem prior to the hurricane is hypothesised to be the main factor controlling the absence of forest recovery. We suggest that human-degraded mangroves will be weakened in the face of such extreme events. We advocate to preserve and restore mangroves in order to guarantee all the valuable ecosystem services they provided.
Egg parasitoid exploitation of plant volatiles induced by single or concurrent attack of a zoophytophagous predator and an invasive phytophagous pest
Authors: Martorana Letizia , Brodeur Jacques , Foti Maria Cristina , Agrò Alfonso , Colazza Stefano , Peri Ezio 
Published: December 2019

AbstractZoophytophagous insect predators can induce physiological responses in plants by activating defence signalling pathways, but whether plants can respond to facultative phytophagy by recruiting natural enemies remains to be investigated. In Y-tube olfactometer bioassays, using a system including a Vicia faba plant, the zoophytophagous predator Podisus maculiventris and the egg parasitoid Telenomus podisi, we first demonstrated that T. podisi females are attracted by broad bean plants damaged by feeding activity of P. maculiventris and on which host egg masses had been laid, while they are not attracted by undamaged plants or plants damaged by feeding activity alone. In a second experiment, we evaluated the impact of the invasive phytophagous pest Halyomorpha halys on this plant volatile-mediated tritrophic communication. Results showed that the invasive herbivorous adults do not induce plants to recruit the native egg parasitoid, but they can disrupt the local infochemical network. In fact, T. podisi females are not attracted by volatiles emitted by plants damaged by H. halys feeding alone or combined with oviposition activity, nor are they attracted by plants concurrently infested by P. maculiventris and H. halys, indicating the specificity in the parasitoid response and the ability of the invasive herbivore in interrupting the semiochemical communication between plants and native egg parasitoids. To the best of our knowledge, this is the first study showing that zoophytophagous predator attacks induce indirect plant defences similarly to those defence strategies adopted by plants as a consequence of single or concurrent infestations of herbivorous insects.
Optimized Biodiesel Production from Waste Cooking Oil (WCO) using Calcium Oxide (CaO) Nano-catalyst
Authors: Degfie Tadesse Anbessie , Mamo Tadios Tesfaye , Mekonnen Yedilfana Setarge 
Published: December 2019

AbstractBiodiesel production from waste cooking oil (WCO) provides an alternative energy means of producing liquid fuels from biomass for various uses. Biodiesel production by recycling WCO and methanol in the presence of calcium oxide (CaO) nano-catalyst offers several benefits such as economic, environmental and waste management. A nano-catalyst of CaO was synthesized by thermal-decomposition method and calcinated at 500 °C followed by characterization using x-ray diffraction (XRD) and scanning electron microscope (SEM) techniques. The XRD results revealed nano-scale crystal sizes at high purity, with a mean particle size of ~29 nm. The SEM images exhibited morphology of irregular shapes and porous structure of the synthesized nanocatalysts. The highest conversion of WCO to biodiesel was estimated to be 96%, at optimized experimental conditions i.e., 50 °C, 1:8 WCO oil to methanol ratio, 1% by weight of catalyst loading rate and 90 minutes reaction time, which is among few highest conversions reported so far. Biodiesel properties were tested according to the American (ASTM D6571) fuel standards. All reactions are carried-out under atmospheric pressure and 1500 rpm of agitation.
Tensin1 expression and function in chronic obstructive pulmonary disease
Authors: Stylianou Panayiota , Clark Katherine , Gooptu Bibek , Smallwood Dawn , Brightling Christopher E. , Amrani Yassine , Roach Katy M. , Bradding Peter 
Published: December 2019

AbstractChronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. Genome wide association studies have shown significant associations between airflow obstruction or COPD with a non-synonymous SNP in the TNS1 gene, which encodes tensin1. However, the expression, cellular distribution and function of tensin1 in human airway tissue and cells are unknown. We therefore examined these characteristics in tissue and cells from controls and people with COPD or asthma. Airway tissue was immunostained for tensin1. Tensin1 expression in cultured human airway smooth muscle cells (HASMCs) was evaluated using qRT-PCR, western blotting and immunofluorescent staining. siRNAs were used to downregulate tensin1 expression. Tensin1 expression was increased in the airway smooth muscle and lamina propria in COPD tissue, but not asthma, when compared to controls. Tensin1 was expressed in HASMCs and upregulated by TGFβ1. TGFβ1 and fibronectin increased the localisation of tensin1 to fibrillar adhesions. Tensin1 and α-smooth muscle actin (αSMA) were strongly co-localised, and tensin1 depletion in HASMCs attenuated both αSMA expression and contraction of collagen gels. In summary, tensin1 expression is increased in COPD airways, and may promote airway obstruction by enhancing the expression of contractile proteins and their localisation to stress fibres in HASMCs.
Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives
Authors: Lo Cascio Filippa , Puangmalai Nicha , Ellsworth Anna , Bucchieri Fabio , Pace Andrea , Palumbo Piccionello Antonio , Kayed Rakez 
Published: December 2019

AbstractThe pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers.
Generation of ECG signals from a reaction-diffusion model spatially discretized
Authors: Quiroz-Juárez M. A. , Jiménez-Ramírez O. , Vázquez-Medina R. , Breña-Medina V. , Aragón J. L. , Barrio R. A. 
Published: December 2019

AbstractWe propose a model to generate electrocardiogram signals based on a discretized reaction-diffusion system to produce a set of three nonlinear oscillators that simulate the main pacemakers in the heart. The model reproduces electrocardiograms from healthy hearts and from patients suffering various well-known rhythm disorders. In particular, it is shown that under ventricular fibrillation, the electrocardiogram signal is chaotic and the transition from sinus rhythm to chaos is consistent with the Ruelle-Takens-Newhouse route to chaos, as experimental studies indicate. The proposed model constitutes a useful tool for research, medical education, and clinical testing purposes. An electronic device based on the model was built for these purposes
Thrombophilic risk factors for retinal vein occlusion
Authors: Vieira Maria J. , Campos António , do Carmo Anália , Arruda Henrique , Martins Joana , Sousa João P. 
Published: December 2019

AbstractThe aim is to study risk factors for retinal vein occlusion (RVO), such as thrombophilic and cardiovascular risk factors (CRF). A retrospective consecutive case series of 60 patients with RVO was made, tested for CRF, hyperhomocysteinemia, lupic anticoagulant, antiphospholipid antibody and 5 gene variants: factor V (FV) Leiden (G1691A), factor II (PT G20210A), 5,1-methylenetetra-hydrofolate reductase (MTHFR; 677 C > T and 1298 A > C), plasminogen activator inhibitor 1 (PAI-1; 4 G/5 G). More than 1 CRF were present in 36 patients (60%), which had a significantly higher mean age at diagnosis (66.7 ± 12.9 versus 59.5 ± 13.7 with ≤1 CRF, [t(57) = −2.05, p = 0.045, d = 0.54). Patients with thermolabile MTHFR forms with decreased enzyme activity (T677T or C677T/A1298C) had a significant lower mean age [57.6 ± 15.1; t (58) = 3.32; p = 0.002; d = 0.846] than patients with normal MTHFR enzyme activity (68.5 ± 10.2). Regarding CRF and thermolabile forms of MTHFR, the mean age at diagnosis could be significantly predicted [F(2,56) = 7.18; p = 0.002] by the equation: 64.8 − 10.3 × (thermolabile MTHFR) − 5.31 × ( ≤ 1CRF). Screening of MTHFR polymorphisms may be useful in younger RVO patients, particularly when multiple CRF are absent.
Dynamics, nanomechanics and signal transduction in reelin repeats
Authors: Mikulska-Ruminska Karolina , Strzelecki Janusz , Nowak Wieslaw 
Published: December 2019

AbstractReelin is a large glycoprotein controlling brain development and cell adhesion. It regulates the positioning of neurons, as well as neurotransmission and memory formation. Perturbations in reelin signaling are linked to psychiatric disorders. Reelin participates in signal transduction by binding to the lipoprotein receptors VLDLR and ApoER2 through its central region. This part is rich in repeating BNR-EGF-BNR modules. We used standard molecular dynamics, steered molecular dynamics, and perturbation response scanning computational methods to characterize unique dynamical properties of reelin modules involved in signaling. Each module has specific sensors and effectors arranged in a similar topology. In the modules studied, disulfide bridges play a protective role, probably making both selective binding and protease activity of reelin possible. Results of single reelin molecule stretching by atomic force microscopy provide the first data on the mechanical stability of individual reelin domains. The forces required for partial unfolding of the modules studied are below 60 pN.