bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of ZnPc and of an amine derivative to inactivate Glioblastoma cells by Photodynamic Therapy: an in vitro comparative study
Authors: Velazquez Fabiola N. , Miretti Mariana , Baumgartner Maria T. , Caputto Beatriz L. , Tempesti Tomas C. , Prucca César G. 
Published: February 2019

AbstractGlioblastoma multiforme is considered to be one of the most aggressive types of tumors of the central nervous system, with a poor prognosis and short survival periods of ~ one year. The current protocol for glioblastoma treatment includes the surgical excision of the primary tumor followed by radio and chemotherapy. Photodynamic therapy (PDT) is considered a promising strategy for the treatment of several types of tumors. Phthalocyanines (Pcs) are good photosensitizers (PSs) for PDT because they induce cell death in several cellular models. ZnPc (Zn(II)phthalocyanine) is a well-known Pc, extensively tested in different cells and tumor models, but its evaluation on a glioblastoma model has been poorly studied. Herein, we compare the capacity of ZnPc and one of its derivatives, Zn(II)tetraminephthalocyanine (TAZnPc), to photoinactivate glioblastoma cells (T98G, MO59, LN229 and U87-MG) in culture. We measured the cellular uptake, the toxicity in the dark and the subcellular localization of the different Pcs, as well as the clonogenic capacity of surviving cells after PDT. The mechanism of cell death induced after PDT was determined by measuring caspase 3 activation, DNA fragmentation, phosphatidylserine externalization, mitochondrial morphological changes and loss of mitochondrial membrane potential as well as lysosomal membrane integrity. Overall, ZnPc and TAZnPc present good properties to be used as PSs with photoinactivation capacity on glioblastoma cells.
A T7 autogene-based hybrid mRNA/DNA system for long-term shRNA expression in cytoplasm without inefficient nuclear entry
Authors: Kwak Seo Young , Han Hee Dong , Ahn Hyung Jun 
Published: February 2019

AbstractThe transient silencing effects currently demonstrated by nonviral siRNA delivery systems limit the therapeutic utility of RNAi, but it remains a technical challenge to prolong duration of gene silencing. We have developed a T7 autogene-based hybrid mRNA/DNA system to enable long-term expression of shRNA in cytoplasm in vitro and in vivo. This hybrid mRNA/DNA system consists of T7 polymerase (T7pol) mRNA, pT7/shRNA-encoding DNA fragment and T7 autogene plasmid, and it can generate higher levels of T7pol proteins, compared to pCMV-triggering T7 autogene system, especially without the need of nuclear entry of any gene. A large amount of T7pol proteins produced are used to induce pT7-driven expression of shRNA in cytoplasm, and through cellular processing of RNA hairpins, mature siRNAs are generated for more than 13 days. We here demonstrate that a single liposomal delivery of this hybrid system leads to the long-term silencing effects in vitro and in vivo, in contrast to the conventional siRNA methods relying on the repeated administrations every 2 or 3 days. These sustainable shRNA expression properties in cytoplasm can provide an efficient strategy to address the limitations caused by shRNA-encoding plasmid DNA systems such as low nuclear entry efficiency and short-term silencing effect. The development of long-term shRNA expression system in vivo could scale down administration frequency of RNAi therapeutics in the treatment of chronic diseases, thereby increasing its clinical utility.
The kidney anion exchanger 1 affects tight junction properties via claudin-4
Authors: Lashhab Rawad , Rumley Alina C. , Arutyunov Denis , Rizvi Midhat , You Charlotte , Dimke Henrik , Touret Nicolas , Zimmermann Richard , Jung Martin , Chen Xing-Zhen , Alexander Todd , Cordat Emmanuelle 
Published: February 2019

AbstractIn the renal collecting duct, intercalated cells regulate acid-base balance by effluxing protons through the v-H+-ATPase, and bicarbonate via apical pendrin or the basolateral kidney anion exchanger 1 (kAE1). Additionally, collecting duct cells play an essential role in transepithelial absorption of sodium and chloride. Expression of kAE1 in polarized MDCK I cells was previously shown to decrease trans-epithelial electrical resistance (TEER), suggesting a novel role for kAE1 in paracellular permeability. In our study, we not only confirmed that inducible expression of kAE1 in mIMCD3 cells decreased TEER but we also observed (i) increased epithelial absolute permeability to both sodium and chloride, and (ii) that this effect was dependent on kAE1 activity. Further, kAE1 regulated tight junction properties through the tight junction protein claudin-4, a protein with which it physically interacts and colocalizes. These findings unveil a novel interaction between the junctional protein claudin-4 and the kidney anion exchanger, which may be relevant to ion and/or pH homeostasis.
Unique properties of PTEN-L contribute to neuroprotection in response to ischemic-like stress
Authors: Jochner Magdalena C. E. , An Junfeng , Lättig-Tünnemann Gisela , Kirchner Marieluise , Dagane Alina , Dittmar Gunnar , Dirnagl Ulrich , Eickholt Britta J. , Harms Christoph 
Published: February 2019

AbstractPhosphatase and tensin homolog (PTEN) signalling might influence neuronal survival after brain ischemia. However, the influence of the less studied longer variant termed PTEN-L (or PTENα) has not been studied to date. Therefore, we examined the translational variant PTEN-L in the context of neuronal survival. We identified PTEN-L by proteomics in murine neuronal cultures and brain lysates and established a novel model to analyse PTEN or PTEN-L variants independently in vitro while avoiding overexpression. We found that PTEN-L, unlike PTEN, localises predominantly in the cytosol and translocates to the nucleus 10–20 minutes after glutamate stress. Genomic ablation of PTEN and PTEN-L increased neuronal susceptibility to oxygen-glucose deprivation. This effect was rescued by expression of either PTEN-L indicating that both PTEN isoforms might contribute to a neuroprotective response. However, in direct comparison, PTEN-L replaced neurons were protected against ischemic-like stress compared to neurons expressing PTEN. Neurons expressing strictly nuclear PTEN-L NLS showed increased vulnerability, indicating that nuclear PTEN-L alone is not sufficient in protecting against stress. We identified mutually exclusive binding partners of PTEN-L or PTEN in cytosolic or nuclear fractions, which were regulated after ischemic-like stress. GRB2-associated-binding protein 2, which is known to interact with phosphoinositol-3-kinase, was enriched specifically with PTEN-L in the cytosol in proximity to the plasma membrane and their interaction was lost after glutamate exposure. The present study revealed that PTEN and PTEN-L have distinct functions in response to stress and might be involved in different mechanisms of neuroprotection.
Nasal mucus glutathione transferase activity and impact on olfactory perception and neonatal behavior
Authors: Robert-Hazotte Aline , Faure Philippe , Neiers Fabrice , Potin Catherine , Artur Yves , Coureaud Gérard , Heydel Jean-Marie 
Published: February 2019

AbstractIn olfaction, to preserve the sensitivity of the response, the bioavailability of odor molecules is under the control of odorant-metabolizing enzymes (OMEs) expressed in the olfactory neuroepithelium. Although this enzymatic regulation has been shown to be involved in olfactory receptor activation and perceptual responses, it remains widely underestimated in vertebrates. In particular, the possible activity of OMEs in the nasal mucus, i.e. the aqueous layer that lined the nasal epithelium and forms the interface for airborne odorants to reach the olfactory sensory neurons, is poorly known. Here, we used the well-described model of the mammary pheromone (MP) and behavioral response in rabbit neonates to challenge the function of nasal mucus metabolism in an unprecedented way. First, we showed, in the olfactory epithelium, a rapid glutathione transferase activity toward the MP by ex vivo real-time mass spectrometry (PTR-MS) which supported an activity in the closest vicinity of both the odorants and olfactory receptors. Indeed and second, both the presence and activity of glutathione transferases were evidenced in the nasal mucus of neonates using proteomic and HPLC analysis respectively. Finally, we strikingly demonstrated that the deregulation of the MP metabolism by in vivo mucus washing modulates the newborn rabbit behavioral responsiveness to the MP. This is a step forward in the demonstration of the critical function of OMEs especially in the mucus, which is at the nasal front line of interaction with odorants and potentially subjected to physiopathological changes.
Modeling ErbB2-p130Cas interaction to design new potential anticancer agents
Authors: Costamagna Andrea , Rossi Sebastiano Matteo , Natalini Dora , Simoni Matilde , Valabrega Giorgio , Defilippi Paola , Visentin Sonja , Ermondi Giuseppe , Turco Emilia , Caron Giulia , Cabodi Sara 
Published: February 2019

AbstractThe ErbB2 receptor tyrosine kinase is overexpressed in approximately 15–20% of breast tumors and associated with aggressive disease and poor clinical outcome. p130Cas represents a nodal scaffold protein regulating cell survival, migration and proliferation in normal and pathological contexts. p130Cas overexpression in ErbB2 human breast cancer correlates with poor prognosis and metastasis formation. Recent data indicate that p130Cas association to ErbB2 protects ErbB2 from degradation, thus enhancing tumorigenesis. Therefore, inhibiting p130Cas/ErbB2 interaction might represent a new therapeutic strategy to target breast cancer. Here we demonstrate by performing Molecular Modeling, Molecular Dynamics, dot blot, ELISA and fluorescence quenching experiments, that p130Cas binds directly to ErbB2. Then, by structure-based virtual screening, we identified two potential inhibitors of p130Cas/ErbB2 interaction. Their experimental validation was performed in vitro and in ErbB2-positive breast cancer cellular models. The results highlight that both compounds interfere with p130Cas/ErbB2 binding and significantly affect cell proliferation and sensitivity to Trastuzumab. Overall, this study identifies p130Cas/ErbB2 complex as a potential breast cancer target revealing new therapeutic perspectives for protein-protein interaction (PPI).
Integrative Analysis Revealing Human Adipose-Specific Genes and Consolidating Obesity Loci
Authors: Ahn Jinsoo , Wu Huiguang , Lee Kichoon 
Published: February 2019

AbstractIdentification of adipose-specific genes has contributed to an understanding of mechanisms underlying adipocyte development and obesity. Herein, our analyses of the recent Genotype-Tissue Expression (GTEx) database revealed 38 adipose-specific/enhanced protein coding genes, among which 3 genes were novel adipose-specific, and 414 highly differentially expressed genes (DEGs) between subcutaneous and omental adipose depots. By integrative analyses of genome-wide association studies (GWASs), 14 adipose-specific/enhanced genes and 60 DEGs were found to be associated with obesity-related traits and diseases, consolidating evidence for contribution of these genes to the regional fat distribution and obesity phenotypes. In addition, expression of HOXC cluster was up-regulated in subcutaneous adipose tissue, and the majority of the HOXB cluster was expressed highly in omental adipose tissue, indicating differential expression patterns of HOX clusters in adipose depots. Our findings on the distinct gene expression profiles in adipose tissue and their relation to obesity provide an important foundation for future functional biological studies and therapeutic targets in obesity and associated diseases.
Abrupt changes of hydrothermal activity in a lava dome detected by combined seismic and muon monitoring
Authors: Le Gonidec Y. , Rosas-Carbajal M. , Bremond d’Ars J. de , Carlus B. , Ianigro J.-C. , Kergosien B. , Marteau J. , Gibert D. 
Published: February 2019

AbstractThe recent 2014 eruption of the Ontake volcano in Japan recalled that hydrothermal fields of moderately active volcanoes have an unpredictable and hazardous behavior that may endanger human beings. Steam blasts can expel devastating ejecta and create craters of several tens of meters. The management of such hydrothermal events in populated areas is problematic because of their very short time of occurrence. At present no precursory signal is clearly identified as a potential warning of imminent danger. Here we show how the combination of seismic noise monitoring and muon density tomography allows to detect, with an unprecedented space and time resolution, the increase of activity (at timescales of few hours to few days) of a hydrothermal spot located 50 to 100 m below the summit of an active volcano, the La Soufrière of Guadeloupe, in the Lesser Antilles. We show how the combination of those two methods improves the risk evaluation of short-term hazards and the localization of the involved volumes in the volcano. We anticipate that the deployment of networks of various sensors including temperature probes, seismic antennas and cosmic muon telescopes around such volcanoes could valuably contribute to early warning decisions.
Detection of Mycobacterium leprae DNA in soil: multiple needles in the haystack
Authors: Tió-Coma Maria , Wijnands Thomas , Pierneef Louise , Schilling Anna Katarina , Alam Korshed , Roy Johan Chandra , Faber William R. , Menke Henk , Pieters Toine , Stevenson Karen , Richardus Jan Hendrik , Geluk Annemieke 
Published: February 2019

AbstractLeprosy is an infectious disease caused by Mycobacterium leprae affecting the skin and nerves. Despite decades of availability of adequate treatment, transmission is unabated and transmission routes are not completely understood. Despite the general assumption that untreated M. leprae infected humans represent the major source of transmission, scarce reports indicate that environmental sources could also play a role as a reservoir. We investigated whether M. leprae DNA is present in soil of regions where leprosy is endemic or areas with possible animal reservoirs (armadillos and red squirrels). Soil samples (n = 73) were collected in Bangladesh, Suriname and the British Isles. Presence of M. leprae DNA was determined by RLEP PCR and genotypes were further identified by Sanger sequencing. M. leprae DNA was identified in 16.0% of soil from houses of leprosy patients (Bangladesh), in 10.7% from armadillos’ holes (Suriname) and in 5% from the habitat of lepromatous red squirrels (British Isles). Genotype 1 was found in Bangladesh whilst in Suriname the genotype was 1 or 2. M. leprae DNA can be detected in soil near human and animal sources, suggesting that environmental sources represent (temporary) reservoirs for M. leprae.
Multilevel information storage using magnetoelastic layer stacks
Authors: Pattnaik D. P. , Beardsley R. P. , Love C. , Cavill S. A. , Edmonds K. W. , Rushforth A. W. 
Published: February 2019

AbstractThe use of voltages to control magnetisation via the inverse magnetostriction effect in piezoelectric/ferromagnet heterostructures holds promise for ultra-low energy information storage technologies. Epitaxial galfenol, an alloy of iron and gallium, has been shown to be a highly suitable material for such devices because it possesses biaxial anisotropy and large magnetostriction. Here we experimentally investigate the properties of galfenol/spacer/galfenol structures in which the compositions of the galfenol layers are varied in order to produce different strengths of the magnetic anisotropy and magnetostriction constants. Based upon these layers, we propose and simulate the operation of an information storage device that can operate as an energy efficient multilevel memory cell.
Adiponectin is associated with cardio-metabolic traits in Mexican children
Authors: He Juehua , Stryjecki Carolina , Reddon Hudson , Peralta-Romero Jesus , Karam-Araujo Roberto , Suarez Fernando , Gomez-Zamudio Jaime , Burguete-Garcia Ana , Alyass Akram , Cruz Miguel , Meyre David 
Published: February 2019

AbstractThe adipocyte-derived adiponectin hormone bridges obesity and its cardio-metabolic complications. Genetic variants at the ADIPOQ locus, in ADIPOR1, and ADIPOR2 have been associated with adiponectin concentrations and cardio-metabolic complications in diverse ethnicities. However, no studies have examined these associations in Mexican children. We recruited 1 457 Mexican children from Mexico City. Six genetic variants in or near ADIPOQ (rs182052, rs2241766, rs266729, rs822393), ADIPOR1 (rs10920533), and ADIPOR2 (rs11061971) were genotyped. Associations between serum adiponectin, genetic variants, and cardio-metabolic traits were assessed using linear and logistic regressions adjusted for age, sex, and recruitment center. Serum adiponectin concentration was negatively associated with body mass index, waist to hip ratio, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, dyslipidemia and overweight/obesity status (7.76 × 10−40 ≤ p ≤ 3.00 × 10−3). No significant associations between genetic variants in ADIPOQ, ADIPOR1, and ADIPOR2 and serum adiponectin concentration were identified (all p ≥ 0.30). No significant associations between the six genetic variants and cardio-metabolic traits were observed after Bonferroni correction (all p < 6.9 × 10−4). Our study suggests strong associations between circulating adiponectin concentration and cardio-metabolic traits in Mexican children.
Microfluidic model systems used to emulate processes occurring during soft particle filtration
Authors: Bouhid de Aguiar Izabella , Meireles Martine , Bouchoux Antoine , Schroën Karin 
Published: February 2019

AbstractCake layer formation in membrane processes is an inevitable phenomenon. For hard particles, especially cake porosity and thickness determine the membrane flux, but when the particles forming the cake are soft, the variables one has to take into account in the prediction of cake behavior increase considerably. In this work we investigate the behavior of soft polyacrylamide microgels in microfluidic model membranes through optical microscopy for in situ observation both under regular flow and under enhanced gravity conditions. Particles larger than the pore are able to pass through deformation and deswelling. We find that membrane clogging time and cake formation is not dependent on the applied pressure but rather on particle and membrane pore properties. Furthermore, we found that particle deposits subjected to low pressures and low g forces deform in a totally reversible fashion. Particle deposits subjected to higher pressures only deform reversibly if they can re-swell due to capillary forces, otherwise irreversible compression is observed. For membrane processes this implies that when using deformable particles, the pore size is not a good indicator for membrane performance, and cake formation can have much more severe consequences compared to hard particles due to the sometimes-irreversible nature of soft particle compression.
Cold-priming of chloroplast ROS signalling is developmentally regulated and is locally controlled at the thylakoid membrane
Authors: van Buer Jörn , Prescher Andreas , Baier Margarete 
Published: February 2019

Abstract24 h exposure to 4 °C primes Arabidopsis thaliana in the pre-bolting rosette stage for several days against full cold activation of the ROS responsive genes ZAT10 and BAP1 and causes stronger cold-induction of pleiotropically stress-regulated genes. Transient over-expression of thylakoid ascorbate peroxidase (tAPX) at 20 °C mimicked and tAPX transcript silencing antagonized cold-priming of ZAT10 expression. The tAPX effect could not be replaced by over-expression of stromal ascorbate peroxidase (sAPX) demonstrating that priming is specific to regulation of tAPX availability and, consequently, regulated locally at the thylakoid membrane. Arabidopsis acquired cold primability in the early rosette stage between 2 and 4 weeks. During further rosette development, primability was widely maintained in the oldest leaves. Later formed and later maturing leaves were not primable demonstrating that priming is stronger regulated with plant age than with leaf age. In 4-week-old plants, which were strongest primable, the memory was fully erasable and lost seven days after priming. In summary, we conclude that cold-priming of chloroplast-to-nucleus ROS signalling by transient post-stress induction of tAPX transcription is a strategy to modify cell signalling for some time without affecting the alertness for activation of cold acclimation responses.
Endothelin neurotransmitter signalling controls zebrafish social behaviour
Authors: Carreño Gutiérrez Héctor , Colanesi Sarah , Cooper Ben , Reichmann Florian , Young Andrew M. J. , Kelsh Robert N. , Norton William H. J. 
Published: February 2019

AbstractThe formation of social groups is an adaptive behaviour that can provide protection from predators, improve foraging and facilitate social learning. However, the costs of proximity can include competition for resources, aggression and kleptoparasitism meaning that the decision whether to interact represents a trade-off. Here we show that zebrafish harbouring a mutation inendothelin receptor aa(ednraa) form less cohesive shoals than wild-types.ednraa−/−mutants exhibit heightened aggression and decreased whole-body cortisol levels suggesting that they are dominant. These behavioural changes correlate with a reduction of parvocellular arginine vasopressin (AVP)-positive neurons in the preoptic area, an increase in the size of magnocellular AVP neurons and a higher concentration of 5-HT and dopamine in the brain. Manipulation of AVP or 5-HT signalling can rescue the shoaling phenotype ofednraa−/−providing an insight into how the brain controls social interactions.
Inhibitory effects of polysorbate 80 on MRSA biofilm formed on different substrates including dermal tissue
Authors: Ueda Yutaka , Mashima Kota , Miyazaki Motoyasu , Hara Shuuji , Takata Tohru , Kamimura Hidetoshi , Takagi Satoshi , Jimi Shiro 
Published: February 2019

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) forms biofilms on necrotic tissues and medical devices, and causes persistent infections. Surfactants act on biofilms, but their mode of action is still unknown. If used in the clinic, cytotoxicity in tissues should be minimized. In this study, we investigated the inhibitory effect of four different surfactants on MRSA biofilm formation, and found that a nonionic surfactant, polysorbate 80 (PS80), was the most suitable. The biofilm inhibitory effects resulted from the inhibition of bacterial adhesion to substrates rather than biofilm disruption, and the effective dose was less cytotoxic for 3T3 fibroblasts. However, the effects were substrate-dependent: positive for plastic, silicon, and dermal tissues, but negative for stainless-steel. These results indicate that PS80 is effective for prevention of biofilms formed by MRSA on tissues and foreign bodies. Therefore, PS80 could be used in medical practice as a washing solution for wounds and/or pretreatment of indwelling catheters.