bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro and intracellular activities of frog skin temporins against Legionella pneumophila and its eukaryotic hosts
Authors: Crépin Alexandre , Jégou Jean-François , André Sonia , Ecale Florine , Croitoru Anastasia , Cantereau Anne , Berjeaud Jean-Marc , Ladram Ali , Verdon Julien 
Published: March 2020

AbstractTemporin-SHa (SHa) is a small cationic host defence peptide (HDP) produced in skin secretions of the Sahara frog Pelophylax saharicus. This peptide has a broad-spectrum activity, efficiently targeting bacteria, parasites and viruses. Noticeably, SHa has demonstrated an ability to kill Leishmania infantum parasites (amastigotes) within macrophages. Recently, an analog of SHa with an increased net positive charge, named [K3]SHa, has been designed to improve those activities. SHa and [K3]SHa were both shown to exhibit leishmanicidal activity mainly by permeabilization of cell membranes but could also induce apoptotis-like death. Temporins are usually poorly active against Gram-negative bacteria whereas many of these species are of public health interest. Among them, Legionella pneumophila, the etiological agent of Legionnaire’s disease, is of major concern. Indeed, this bacterium adopts an intracellular lifestyle and replicate inside alveolar macrophages likewise inside its numerous protozoan hosts. Despite several authors have studied the antimicrobial activity of many compounds on L. pneumophila released from host cells, nothing is known about activity on intracellular L. pneumophila within their hosts, and subsequently mechanisms of action that could be involved. Here, we showed for the first time that SHa and [K3]SHa were active towards several species of Legionella. Both peptides displayed bactericidal activity and caused a loss of the bacterial envelope integrity leading to a rapid drop in cell viability. Regarding amoebae and THP-1-derived macrophages, SHa was less toxic than [K3]SHa and exhibited low half maximal lethal concentrations (LC50). When used at non-toxic concentration (6.25 µM), SHa killed more than 90% L. pneumophila within amoebae and around 50% within macrophages. Using SHa labeled with the fluorescent dye Cy5, we showed an evenly diffusion within cells except in vacuoles. Moreover, SHa was able to enter the nucleus of amoebae and accumulate in the nucleolus. This subcellular localization seemed specific as macrophages nucleoli remained unlabeled. Finally, no modifications in the expression of cytokines and HDPs were recorded when macrophages were treated with 6.25 µM SHa. By combining all data, we showed that temporin-SHa decreases the intracellular L. pneumophila load within amoebae and macrophages without being toxic for eukaryotic cells. This peptide was also able to reach the nucleolus of amoebae but was not capable to penetrate inside vacuoles. These data are in favor of an indirect action of SHa towards intracellular Legionella and make this peptide a promising template for further developments.
Handgrip strength, dynapenia, and mental health in older Koreans
Authors: Noh Hye-Mi , Park Yong Soon 
Published: March 2020

AbstractThis study examined associations between muscle strength and mental health among 2,652 elderly Koreans who participated in the 2015 and 2017 Korea National Health and Nutrition Examination Survey. We measured absolute handgrip strength and calculated handgrip strength relative to body mass index. Dynapenia criteria followed that of the Asian Working Group for Sarcopenia. Questionnaires were used to assess mental health indicators including suicidal ideation, depressed mood, and stress status. Among participants, 18.6%, 14.9%, and 6.7% reported stress, depressed mood, and suicidal ideation, respectively. Dynapenia prevalence was 25.1%. Adjusted odds ratios of stress, depressed mood, and suicidal ideation for men with dynapenia were 2.15, 2.30, and 2.11, respectively. Significant associations were absent among women. For men, handgrip strength and relative handgrip strength were inversely associated with risk of stress, depressed mood, and suicidal ideation. For women, handgrip strength and relative handgrip strength were inversely associated with the risk of stress, but not of depressed mood and suicidal ideation. In conclusion, all muscle-strength indices were associated with mental health risks among older men. In older women, low handgrip strength and relative handgrip strength were associated with increased stress. Muscle strength could be a clinical marker of poor mental health in older adults.
Disruption of the kringle 1 domain of prothrombin leads to late onset mortality in zebrafish
Authors: Grzegorski Steven J. , Hu Zhilian , Liu Yang , Yu Xinge , Ferguson Allison C. , Madarati Hasam , Friedmann Alexander P. , Reyon Deepak , Kim Paul Y. , Kretz Colin A. , Joung J. Keith , Shavit Jordan A. 
Published: March 2020

AbstractThe ability to prevent blood loss in response to injury is a conserved function of all vertebrates. Complete deficiency of the central clotting enzyme prothrombin has never been observed in humans and is incompatible with postnatal life in mice, thus limiting the ability to study its role in vivo. Zebrafish are able to tolerate severe hemostatic deficiencies that are lethal in mammals. We have generated a targeted genetic deletion in the kringle 1 domain of zebrafish prothrombin. Homozygous mutant embryos develop normally into the mid-juvenile stage but demonstrate complete mortality by 2 months of age primarily due to internal hemorrhage. Mutants are unable to form occlusive venous and arterial thrombi in response to endothelial injury, a defect that was phenocopied using direct oral anticoagulants. Human prothrombin engineered with the equivalent mutation exhibits a severe reduction in secretion, thrombin generation, and fibrinogen cleavage. Together, these data demonstrate the conserved function of thrombin in zebrafish and provide insight into the role of kringle 1 in prothrombin maturation and activity. Understanding how zebrafish are able to develop normally and survive into early adulthood without thrombin activity will provide important insight into its pleiotropic functions as well as the management of patients with bleeding disorders.
A Systematic Study of the Impact of Estrogens and Selective Estrogen Receptor Modulators on Prostate Cancer Cell Proliferation
Authors: Lafront Camille , Germain Lucas , Weidmann Cindy , Audet-Walsh Étienne 
Published: March 2020

AbstractThe estrogen signaling pathway has been reported to modulate prostate cancer (PCa) progression through the activity of estrogen receptors α and β (ERα and ERβ). Given that selective estrogen receptor modulators (SERMs) are used to treat breast cancer, ERs have been proposed as attractive therapeutic targets in PCa. However, many inconsistencies regarding the expression of ERs and the efficacy of SERMs for PCa treatment exist, notably due to the use of ERβ antibodies lacking specificity and treatments with high SERM concentrations leading to off-target effects. To end this confusion, our objective was to study the impact of estrogenic and anti-estrogenic ligands in well-studied in vitro PCa models with appropriate controls, dosages, and ER subtype-specific antibodies. When using physiologically relevant concentrations of nine estrogenic/anti-estrogenic compounds, including five SERMs, we observed no significant modulation of PCa cell proliferation. Using RNA-seq and validated antibodies, we demonstrate that these PCa models do not express ERs. In contrast, RNA-seq from PCa samples from patients have detectable expression of ERα. Overall, our study reveals that commonly used PCa models are inappropriate to study ERs and indicate that usage of alternative models is essential to properly assess the roles of the estrogen signaling pathway in PCa.
Networks and long-range mobility in cities: A study of more than one billion taxi trips in New York City
Authors: Riascos A. P. , Mateos José L. 
Published: March 2020

AbstractWe analyze the massive data set of more than one billion taxi trips in New York City, from January 2009 to December 2015. With these records of seven years, we generate an origin-destination matrix that has information of a vast number of trips. The mobility and flow of taxis can be described as a directed weighted network that connects different zones of high demand for taxis. This network has in and out degrees that follow a stretched exponential and a power law with an exponential cutoff distributions, respectively. Using the origin-destination matrix, we obtain a rank, called "OD rank”, analogous to the page rank of Google, that gives the more relevant places in New York City in terms of taxi trips. We introduced a model that captures the local and global dynamics that agrees with the data. Considering the taxi trips as a proxy of human mobility in cities, it might be possible that the long-range mobility found for New York City would be a general feature in other large cities around the world.
Modelling predictive gender- and gestation-specific weight reference centiles for preterm infants using a population-based cohort study
Authors: Watkins W. John , Farewell Daniel , Banerjee Sujoy , Nasef Hesham , James Anitha , Chakraborty Mallinath 
Published: March 2020

AbstractWe aimed to model longitudinal data to create predictive growth charts for weight in preterm infants from birth till discharge, that took into account the differing growth rates post-birth when compared to in-utero growth and therefore was more representative of the data than the UK1990 reference charts. Data from birth until discharge (or death), was collected and rigorously cleaned for all infants born at <32 weeks of gestation over a 4-year period. Means and standard deviations from the UK1990 reference charts were used to compute standard deviation scores (SDS) for our cohort. 2/3rd of the data was randomly selected and used to create gestation and gender-specific predictive weight centile lines through novel application of mixed modelling methods. The remaining 1/3rd of the data was used to test model fit by comparing expected vs actual weights for the new model with those predicted by the UK1990 model. Data from 1,510 preterm infants was analysed. 1067 of these were used to produce the predictive model. Weekly SDS were significantly lower than predicted throughout hospital stay for all gestation groups when compared with UK1990 data. The test data (n = 539) fitted the new centile lines substantially better than those modelled by the UK1990 centile lines. Mixed modelling of longitudinal data produced new predictive references for weight centiles of preterm infants. A large population-based prospective study is needed to produce representative longitudinal reference growth charts using these methods.
Evidence for subcritical rupture of injection-induced earthquakes
Authors: Orlecka-Sikora Beata , Cielesta Szymon 
Published: March 2020

AbstractSeismicity induced by geo-engineering operations may be hazardous for people, infrastructure and the environment. The crucial information for assessing induced seismic hazards and related risks is knowledge of the time-dependent strength of rocks and the deformation due to fluid injection. Our studies of seismic and injection data from a geothermal field indicate that pressurized injections lead to rock fracturing at stress levels below the rock toughness, i.e., subcritical fracture growth. We provide a relation between the rate of this subcritical fracture growth and the injection rate. Based on this relation, we estimate the maximum subcritical magnitude. We hypothesize that subcritical fracture growth may be controlled by the amount of stress asymmetry, i.e., the relative values of the principal stresses. We discuss the conditions under which the subcritical fracturing regime can transform to a critical state and critical rupture may occur. We present the possibility of using these results in the operational reservoir to manage seismic hazards.
Retinal biomarkers and pharmacological targets for Hermansky-Pudlak syndrome 7
Authors: Romano Giovanni Luca , Platania Chiara Bianca Maria , Leggio Gian Marco , Torrisi Sebastiano Alfio , Giunta Salvatore , Salomone Salvatore , Purrello Michele , Ragusa Marco , Barbagallo Cristina , Giblin Frank J. , Mastrogiacomo Rosa , Managò Francesca , Cammalleri Maurizio , Papaleo Francesco , Drago Filippo , Bucolo Claudio 
Published: March 2020

AbstractDeletion of dystrobrevin binding protein 1 has been linked to Hermansky-Pudlak syndrome type 7 (HPS-7), a rare disease characterized by oculocutaneous albinism and retinal dysfunction. We studied dysbindin-1 null mutant mice (Dys−/−) to shed light on retinal neurodevelopment defects in HPS-7. We analyzed the expression of a focused set of miRNAs in retina of wild type (WT), Dys+/− and Dys−/− mice. We also investigated the retinal function of these mice through electroretinography (ERG). We found that miR-101-3p, miR-137, miR-186-5p, miR-326, miR-382-5p and miR-876-5p were up-regulated in Dys−/−mice retina. Dys−/− mice showed significant increased b-wave in ERG, compared to WT mice. Bioinformatic analysis highlighted that dysregulated miRNAs target synaptic plasticity and dopaminergic signaling pathways, affecting retinal functions of Dys−/− mice. Overall, the data indicate potential mechanisms in retinal neurodevelopment of Dys−/− mice, which may have translational significance in HSP-7 patients, both in terms of diagnostic/prognostic biomarkers and novel pharmacological targets.
Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation
Authors: Tretina Kyle , Haidar Malak , Madsen-Bouterse Sally A. , Sakura Takaya , Mfarrej Sara , Fry Lindsay , Chaussepied Marie , Pain Arnab , Knowles Donald P. , Nene Vishvanath M. , Ginsberg Doron , Daubenberger Claudia A. , Bishop Richard P. , Langsley Gordon , Silva Joana C. 
Published: March 2020

AbstractIntracellular pathogens have evolved intricate mechanisms to subvert host cell signaling pathways and ensure their own propagation. A lineage of the protozoan parasite genus Theileria infects bovine leukocytes and induces their uncontrolled proliferation causing a leukemia-like disease. Given the importance of E2F transcription factors in mammalian cell cycle regulation, we investigated the role of E2F signaling in Theileria-induced host cell proliferation. Using comparative genomics and surface plasmon resonance, we identified parasite-derived peptides that have the sequence-specific ability to increase E2F signaling by binding E2F negative regulator Retinoblastoma-1 (RB). Using these peptides as a tool to probe host E2F signaling, we show that the disruption of RB complexes ex vivo leads to activation of E2F-driven transcription and increased leukocyte proliferation in an infection-dependent manner. This result is consistent with existing models and, together, they support a critical role of E2F signaling for Theileria-induced host cell proliferation, and its potential direct manipulation by one or more parasite proteins.
Evaluation of the Effect of Ciprofloxacin and Vancomycin on Mechanical Properties of PMMA Cement; a Preliminary Study on Molecular Weight
Authors: Gandomkarzadeh Marzieh , Moghimi Hamid Reza , Mahboubi Arash 
Published: March 2020

AbstractAntibiotic-loaded bone cement (ALBC) is commonly used in joint replacement therapy for prevention and treatment of bone infection and mechanical properties of the cement is still an important issue. The effects of ciprofloxacin and vancomycin was investigated on mechanical characterization of PMMA bone cement. Different properties of cement containing (0, 2.5, 5 and 10% W/W) antibiotics, including compressive and bending properties, microstructural, porosity and density were evaluated. Both antibiotics significantly reduced the density values and mechanical properties (compressive and flexural strength and modulus) in all groups in comparison to control over first two weeks (p < 0.05). This reduction was due to increased porosity upon antibiotic addition (3.05 and 3.67% for ciprofloxacin and vancomycin, respectively) in comparison to control (2.08%) (p < 0.001) and exposure to aqueous medium. Vancomycin as antibiotic with higher molecular weight (MW = 1485) had significant effect on compressive strength reduction of the cement at high amount compared to ciprofloxacin (MW = 367) (P < 0.01), there was no difference between two antibiotics at lower concentrations (P > 0.05). The effect of antibiotic loading is both molecular weight and drug content dependent. The time is also an important parameter and the second week is the probably optimum time to study mechanical behavior of ALBC.
Very-long-chain fatty acid metabolic capacity of 17-beta-hydroxysteroid dehydrogenase type 12 (HSD17B12) promotes replication of hepatitis C virus and related flaviviruses
Authors: Mohamed Bassim , Mazeaud Clément , Baril Martin , Poirier Donald , Sow Aïssatou Aïcha , Chatel-Chaix Laurent , Titorenko Vladimir , Lamarre Daniel 
Published: March 2020

AbstractFlaviviridae infections represent a major global health burden. By deciphering mechanistic aspects of hepatitis C virus (HCV)-host interactions, one could discover common strategy for inhibiting the replication of related flaviviruses. By elucidating the HCV interactome, we identified the 17-beta-hydroxysteroid dehydrogenase type 12 (HSD17B12) as a human hub of the very-long-chain fatty acid (VLCFA) synthesis pathway and core interactor. Here we show that HSD17B12 knockdown (KD) impairs HCV replication and reduces virion production. Mechanistically, depletion of HSD17B12 induces alterations in VLCFA-containing lipid species and a drastic reduction of lipid droplets (LDs) that play a critical role in virus assembly. Oleic acid supplementation rescues viral RNA replication and production of infectious particles in HSD17B12 depleted cells, supporting a specific role of VLCFA in HCV life cycle. Furthermore, the small-molecule HSD17B12 inhibitor, INH-12, significantly reduces replication and infectious particle production of HCV as well as dengue virus and Zika virus revealing a conserved requirement across Flaviviridae virus family. Overall, the data provide a strong rationale for the advanced evaluation of HSD17B12 inhibition as a promising broad-spectrum antiviral strategy for the treatment of Flaviviridae infections.
Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice
Authors: Komura Shingo , Satake Takashi , Goto Atsushi , Aoki Hitomi , Shibata Hirofumi , Ito Kenji , Hirakawa Akihiro , Yamada Yasuhiro , Akiyama Haruhiko 
Published: March 2020

AbstractTendons are dense fibrous structures that attach muscles to bones. Healing of tendon injuries is a clinical challenge owing to poor regenerative potential and scarring. Here, we created reporter mice that express EGFP, driven by the promoter of the tendon-specific Scleraxis (Scx) transcription-factor gene; we then generated induced pluripotent stem cells (iPSCs) from these mice. Utilising these fluorescently labelled iPSCs, we developed a tenogenic differentiation protocol. The iPSC-derived EGFP-positive cells exhibited elevated expression of tendon-specific genes, including Scx, Mohawk, Tenomodulin, and Fibromodulin, indicating that they have tenocyte-like properties. Finally, we demonstrated that these cells promoted tendon regeneration in mice after transplantation into injured tendons reducing scar formation via paracrine effect. Our data demonstrate that the tenogenic differentiation protocol successfully provided functional cells from iPSCs. We propose that pluripotent stem cell-based therapy using this protocol will provide an effective therapeutic approach for tendon injuries.
A facile template-free strategy for synthesizing hydroxymethyl-poly(3,4-ethylenedioxythiophene) nanospheres
Authors: Jee Chanhyuk , Kang Kyung Seok , Bae Ji-Hong , Jung Hyo Jin , Lim WonBin , Kim Byeong Joo , Huh PilHo 
Published: March 2020

AbstractHydroxymethyl-poly(3,4-ethylenedioxythiophene)(PEDOT-OH) nanospheres self-assembled using physical blowing method, which continually used a syringe, were successfully formed through aqueous solution polymerization under the oxidative initiators. The effect of blowing on the morphological properties of PEDOT-OH was precisely evaluated based on the different amount of initiator. The concentration of ammonium persulfate might be a driving force in the self-assembly process to create the PEDOT-OH nanospheres. The electrical and electrochemical properties of the resulting nanospheres were also characterized using four-point probe and cyclic voltammetry.
Radioguided surgery with β− radiation in pancreatic Neuroendocrine Tumors: a feasibility study
Authors: Collamati Francesco , Maccora Daria , Alfieri Sergio , Bocci Valerio , Cartoni Antonella , Collarino Angela , Simoni Micol De , Fischetti Marta , Fratoddi Ilaria , Giordano Alessandro , Mancini-Terracciano Carlo , Mirabelli Riccardo , Morganti Silvio , Quero Giuseppe , Rotili Dante , Scotognella Teresa , Solfaroli Camillocci Elena , Traini Giacomo , Venditti Iole , Faccini Riccardo 
Published: March 2020

AbstractThe possibility to use β− decaying isotopes for radioguided surgery (RGS) has been recently proposed, and first promising tests on ex-vivo samples of Meningioma and intestinal Neuroendocrine Tumor (NET) have been published. This paper reports a study of the uptake of 68Ga-DOTATOC in pancreatic NETs (pNETs) in order to assess the feasibility of a new RGS approach using 90Y-DOTATOC. Tumor and healthy pancreas uptakes were estimated from 68Ga-DOTATOC PET/CT scans of 30 patients with pNETs. From the obtained SUVs (Standardised Uptake Value) and TNRs (Tumor Non tumor Ratio), an analysis algorithm relying on a Monte Carlo simulation of the detector has been applied to evaluate the performances of the proposed technique. Almost all considered patients resulted to be compatible with the application of β−-RGS assuming to administer 1.5 MBq/kg of activity of 90Y-DOTATOC 24 h before surgery, and a sampling time of few seconds. In just 2 cases the technique would have required a mildly increased amount of activity or of sampling time. Despite a high physiological uptake of 68Ga-DOTATOC in the healthy pancreas, the proposed RGS technique promises to be effective. This approach allows RGS to find application also in pancreatic diseases, where traditional techniques are not viable.