bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of mitochondrial dynamics proteins are a targetable feature of human tumors
Authors: Anderson Gray R. , Wardell Suzanne E. , Cakir Merve , Yip Catherine , Ahn Yeong-ran , Ali Moiez , Yllanes Alexander P. , Chao Christina A. , McDonnell Donald P. , Wood Kris C. 
Published: April 2018

AbstractAltered mitochondrial dynamics can broadly impact tumor cell physiology. Using genetic and pharmacological profiling of cancer cell lines and human tumors, we here establish that perturbations to the mitochondrial dynamics network also result in specific therapeutic vulnerabilities. In particular, through distinct mechanisms, tumors with increased mitochondrial fragmentation or connectivity are hypersensitive to SMAC mimetics, a class of compounds that induce apoptosis through inhibition of IAPs and for which robust sensitivity biomarkers remain to be identified. Further, because driver oncogenes exert dominant control over mitochondrial dynamics, oncogene-targeted therapies can be used to sensitize tumors to SMAC mimetics via their effects on fission/fusion dynamics. Collectively, these data demonstrate that perturbations to the mitochondrial dynamics network induce targetable vulnerabilities across diverse human tumors and, more broadly, suggest that the altered structures, activities, and trafficking of cellular organelles may facilitate additional cancer therapeutic opportunities.
Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques
Authors: Magnani Diogo M. , Rogers Thomas F. , Maness Nicholas J. , Grubaugh Nathan D. , Beutler Nathan , Bailey Varian K. , Gonzalez-Nieto Lucas , Gutman Martin J. , Pedreño-Lopez Núria , Kwal Jaclyn M. , Ricciardi Michael J. , Myers Tereance A. , Julander Justin G. , Bohm Rudolf P. , Gilbert Margaret H. , Schiro Faith , Aye Pyone P. , Blair Robert V. , Martins Mauricio A. , Falkenstein Kathrine P. , Kaur Amitinder , Curry Christine L. , Kallas Esper G. , Desrosiers Ronald C. , Goldschmidt-Clermont Pascal J. , Whitehead Stephen S. , Andersen Kristian G. , Bonaldo Myrna C. , Lackner Andrew A. , Panganiban Antonito T. , Burton Dennis R. , Watkins David I. 
Published: April 2018

AbstractZika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.
Mesopores induced zero thermal expansion in single-crystal ferroelectrics
Authors: Ren Zhaohui , Zhao Ruoyu , Chen Xing , Li Ming , Li Xiang , Tian He , Zhang Ze , Han Gaorong 
Published: April 2018

AbstractFor many decades, zero thermal expansion materials have been the focus of numerous investigations because of their intriguing physical properties and potential applications in high-precision instruments. Different strategies, such as composites, solid solution and doping, have been developed as promising approaches to obtain zero thermal expansion materials. However, microstructure controlled zero thermal expansion behavior via interface or surface has not been realized. Here we report the observation of an impressive zero thermal expansion (volumetric thermal expansion coefficient, −1.41 × 10−6 K−1, 293–623 K) in single-crystal ferroelectric PbTiO3 fibers with large-scale faceted and enclosed mesopores. The zero thermal expansion behavior is attributed to a synergetic effect of positive thermal expansion near the mesopores due to the oxygen-based polarization screening and negative thermal expansion from an intrinsic ferroelectricity. Our results show that a fascinating surface construction in negative thermal expansion ferroelectric materials could be a promising strategy to realize zero thermal expansion.
Reconstructing phase diagrams from local measurements via Gaussian processes: mapping the temperature-composition space to confidence
Authors: Pradhan Dhiren K. , Kumari Shalini , Strelcov Evgheni , Pradhan Dillip K. , Katiyar Ram S. , Kalinin Sergei V. , Laanait Nouamane , Vasudevan Rama K. 
Published: April 2018

AbstractWe show the ability to map the phase diagram of a relaxor-ferroelectric system as a function of temperature and composition through local hysteresis curve acquisition, with the voltage spectroscopy data being used as a proxy for the (unknown) microscopic state or thermodynamic parameters of materials. Given the discrete nature of the measurement points, we use Gaussian processes to reconstruct hysteresis loops in temperature and voltage space, and compare the results with the raw data and bulk dielectric spectroscopy measurements. The results indicate that the surface transition temperature is similar for all but one composition with respect to the bulk. Through clustering algorithms, we recreate the main features of the bulk diagram, and provide statistical confidence estimates for the reconstructed phase transition temperatures. We validate the method by using Gaussian processes to predict hysteresis loops for a given temperature for a composition unseen by the algorithm, and compare with measurements. These techniques can be used to map phase diagrams from functional materials in an automated fashion, and provide a method for uncertainty quantification and model selection.
ABO Antigens Active Tri- and Disaccharides Microarray to Evaluate C-type Lectin Receptor Binding Preferences
Authors: Shanthamurthy Chethan D. , Jain Prashant , Yehuda Sharon , Monteiro João T. , Leviatan Ben-Arye Shani , Subramani Balamurugan , Lepenies Bernd , Padler-Karavani Vered , Kikkeri Raghavendra 
Published: April 2018

AbstractUnderstanding blood group antigen binding preferences for C-type lectin receptors holds promise for modulating immune responses, since several Gram-negative bacteria express blood group antigens as molecular mimicry to evade immune responses. Herein, we report the synthesis of ABO blood group antigen active tri and disaccharides to investigate the binding specificity with various C-type lectin receptors using glycan microarray. The results of binding preferences show that distinct glycosylation on the galactose and fucose motifs are key for C-type lectin receptor binding and that these interactions occur in a Ca2+-dependent fashion.
Action and object words are differentially anchored in the sensory motor system - A perspective on cognitive embodiment
Authors: Horoufchin Houpand , Bzdok Danilo , Buccino Giovanni , Borghi Anna M. , Binkofski Ferdinand 
Published: April 2018

AbstractEmbodied and grounded cognition theories have assumed that the sensorimotor system is causally involved in processing motor-related language content. Although a causal proof on a single-cell basis is ethically not possible today, the present fMRI study provides confirmation of this longstanding speculation, as far as it is possible with recent methods, employing a new computational approach. More specifically, we were looking for common activation of nouns and objects, and actions and verbs, representing the canonical and mirror neuron system, respectively. Using multivariate pattern analysis, a resulting linear classifier indeed successfully generalized from distinguishing actions from objects in pictures to distinguishing the respective verbs from nouns in written words. Further, these action-related pattern responses were detailed by recently introduced predictive pattern decomposition into the constituent activity atoms and their relative contributions. The findings support the concept of canonical neurons and mirror neurons implementing embodied processes with separate roles in distinguishing objects from actions, and nouns from verbs, respectively. This example of neuronal recycling processing algorithms is consistent with a multimodal brain signature of human action and object concepts. Embodied language theory is thus merged with actual neurobiological implementation.
Focused Ultrasound-enabled Brain Tumor Liquid Biopsy
Authors: Zhu Lifei , Cheng Galen , Ye Dezhuang , Nazeri Arash , Yue Yimei , Liu Weijun , Wang Xiaowei , Dunn Gavin P. , Petti Allegra A. , Leuthardt Eric C. , Chen Hong 
Published: April 2018

AbstractAlthough blood-based liquid biopsies have emerged as a promising non-invasive method to detect biomarkers in various cancers, limited progress has been made for brain tumors. One major obstacle is the blood-brain barrier (BBB), which hinders efficient passage of tumor biomarkers into the peripheral circulation. The objective of this study was to determine whether FUS in combination with microbubbles can enhance the release of biomarkers from the brain tumor to the blood circulation. Two glioblastoma tumor models (U87 and GL261), developed by intracranial injection of respective enhanced green fluorescent protein (eGFP)-transduced glioblastoma cells, were treated by FUS in the presence of systemically injected microbubbles. Effect of FUS on plasma eGFP mRNA levels was determined using quantitative polymerase chain reaction. eGFP mRNA were only detectable in the FUS-treated U87 mice and undetectable in the untreated U87 mice (maximum cycle number set to 40). This finding was replicated in GL261 mice across three different acoustic pressures. The circulating levels of eGFP mRNA were 1,500–4,800 fold higher in the FUS-treated GL261 mice than that of the untreated mice for the three acoustic pressures. This study demonstrated the feasibility of FUS-enabled brain tumor liquid biopsies in two different murine glioma models across different acoustic pressures.
Evaluation of subconjunctival liposomal steroids for the treatment of experimental uveitis
Authors: Wong Chee Wai , Czarny Bertrand , Metselaar Josbert M. , Ho Candice , Ng Si Rui , Barathi Amutha Veluchamy , Storm Gert , Wong Tina T. 
Published: April 2018

AbstractNon-infectious anterior uveitis (AU) is a potentially sight threatening inflammatory condition. The current gold standard for treatment is topical steroids, but low ocular bioavailability and compliance issues with the intensive dosing regimen limit the efficacy of this treatment. Liposomes as a drug delivery system may help to overcome these problems. We studied the efficacy of a PEG-liposomal formulation of liposomal steroids, administered as a single subconjunctival dose, in the treatment of experimental uveitis in rabbit eyes. Rabbits that received subconjunctival liposomal triamcinolone acetonide phosphate (LTAP) or liposomal prednisolone phosphate (LPP) had significantly lower mean inflammatory scores than untreated controls on Day 4 after induction of uveitis (LPP vs controls, p = 0.049) and 8 (LPP vs controls, p = 0.007; LTAP vs controls, p = 0.019), and lower scores than rabbits given topical PredForte1% 4 times a day on Day 8 (p = 0.03). After antigen rechallenge, the subconjunctival liposomal steroid groups continued to have greater suppression of inflammation than untreated controls on Day 11 (p = 0.02). Localization of liposomes in inflamed ocular tissue was confirmed by histology and immunostaining, and persisted in the eye for at least one month. Our study demonstrates that a single subconjunctival injection of liposomal steroids induces effective and sustained anti-inflammatory action.
A unique hybrid-structured surface produced by rapid electrochemical anodization enhances bio-corrosion resistance and bone cell responses of β-type Ti-24Nb-4Zr-8Sn alloy
Authors: Liu Chia-Fei , Lee Tzu-Hsin , Liu Jeng-Fen , Hou Wen-Tao , Li Shu-Jun , Hao Yu-Lin , Pan Haobo , Huang Her-Hsiung 
Published: April 2018

AbstractTi-24Nb-4Zr-8Sn (Ti2448), a new β-type Ti alloy, consists of nontoxic elements and exhibits a low uniaxial tensile elastic modulus of approximately 45 GPa for biomedical implant applications. Nevertheless, the bio-corrosion resistance and biocompatibility of Ti2448 alloys must be improved for long-term clinical use. In this study, a rapid electrochemical anodization treatment was used on Ti2448 alloys to enhance the bio-corrosion resistance and bone cell responses by altering the surface characteristics. The proposed anodization process produces a unique hybrid oxide layer (thickness 50–120 nm) comprising a mesoporous outer section and a dense inner section. Experiment results show that the dense inner section enhances the bio-corrosion resistance. Moreover, the mesoporous surface topography, which is on a similar scale as various biological species, improves the wettability, protein adsorption, focal adhesion complex formation and bone cell differentiation. Outside-in signals can be triggered through the interaction of integrins with the mesoporous topography to form the focal adhesion complex and to further induce osteogenic differentiation pathway. These results demonstrate that the proposed electrochemical anodization process for Ti2448 alloys with a low uniaxial tensile elastic modulus has the potential for biomedical implant applications.
Phenotypic variability between Social Dominance Ranks in laboratory mice
Authors: Varholick Justin A. , Bailoo Jeremy D. , Palme Rupert , Würbel Hanno 
Published: April 2018

AbstractThe laboratory mouse is the most prevalent animal used in experimental procedures in the biomedical and behavioural sciences. Yet, many scientists fail to consider the animals’ social context. Within a cage, mice may differ in their behaviour and physiology depending on their dominance relationships. Therefore, dominance relationships may be a confounding factor in animal experiments. The current study housed male and female C57BL/6ByJ mice in same-sex groups of 5 in standard laboratory conditions and investigated whether dominance hierarchies were present and stable across three weeks, and whether mice of different dominance ranks varied consistently in behaviour and physiology. We found that dominance ranks of most mice changed with time, but were most stable between the 2nd and 3rd week of testing. Phenotypic measures were also highly variable, and we found no relation between dominance rank and phenotype. Further, we found limited evidence that variation in measures of phenotype was associated with cage assignment for either males or females. Taken together, these findings do not lend support to the general assumption that individual variation among mice is larger between cages than within cages.
Feeding young infants with their head in upright position reduces respiratory and ear morbidity
Authors: Avital Avraham , Donchin Milka , Springer Chaim , Cohen Shlomo , Danino Efrat 
Published: April 2018

AbstractThe influence of feeding position of the infant in the pathogenesis of ear and airway diseases has not been well established. We investigated the influence of instructing mothers to feed their 3-month old infants with their head in an upright position on ear and respiratory morbidity during a one-year follow-up. Mothers of 88 infants were instructed by trained nurses to feed their infants with their head in upright position (intervention group). The control group consisted of 75 mothers of infants of similar socioeconomic background who fed their infants without special instructions. Both groups were followed at Maternal-Child-Health clinics. Feeding position was evaluated at the beginning and the end of the twelve-month study, and parent reported morbidity data of both groups were evaluated at every 3-month’s follow-up meeting. Infants from the intervention group were fed at a more upright head position. Parameters of parent reported morbidity evaluated as area under the curve were significantly lower in infants from the intervention group concerning ear diseases, respiratory diseases, prolonged fever episodes, need of bronchodilator inhalations and antibiotic courses compared to the control group. Instructing mothers to feed infants with their head in upright position was accompanied with less morbidity and treatment burden.
HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation
Authors: Mohammadi Hakimeh , Papp Eszter , Cahill Lindsay , Rennie Monique , Banko Nicole , Pinnaduwage Lakmini , Lee Janice , Kibschull Mark , Dunk Caroline , Sled John G. , Serghides Lena 
Published: April 2018

AbstractAdverse birth outcomes are common in HIV-positive pregnant women receiving combination antiretroviral therapy (cART), especially when cART is initiated in early pregnancy. The mechanisms remain poorly understood. Using a mouse model we demonstrate that protease inhibitor based-cART exposure beginning on day 1 of pregnancy was associated with a pro-angiogenic/pro-branching shift in the placenta driven by lower Flt-1 levels and higher Gcm-1 expression. Micro-CT imaging revealed an increase in the number of arterioles in cART-treated placentas, which correlated with fetal growth restriction. Delaying initiation of cART, or supplementing cART-treated mice with progesterone, prevented the pro-angiogenic/pro-branching shift and the associated placenta vascular changes. In agreement with our mouse findings, we observed an increase in the number of terminal-villi capillaries in placentas from HIV-positive cART-exposed women compared to HIV-negative controls. Capillary number was inversely correlated to maternal progesterone levels. Our study provides evidence that cART exposure during pregnancy influences placenta vascular formation that may in turn contribute to fetal growth restriction. Our findings highlight the need for closer investigation of the placenta in HIV-positive pregnancies, particularly for pregnancies exposed to cART from conception, and suggest that progesterone supplementation could be investigated as a possible intervention to improve placenta function in HIV-positive pregnant women.
Self-homodimerization of an actinoporin by disulfide bridging reveals implications for their structure and pore formation
Authors: Valle Aisel , Pérez-Socas Luis Benito , Canet Liem , Hervis Yadira de la Patria , de Armas-Guitart German , Martins-de-Sa Diogo , Lima Jônatas Cunha Barbosa , Souza Adolfo Carlos Barros , Barbosa João Alexandre Ribeiro Gonçalves , de Freitas Sonia Maria , Pazos Isabel Fabiola 
Published: April 2018

AbstractThe Trp111 to Cys mutant of sticholysin I, an actinoporin from Stichodactyla helianthus sea anemone, forms a homodimer via a disulfide bridge. The purified dimer is 193 times less hemolytic than the monomer. Ultracentrifugation, dynamic light scattering and size-exclusion chromatography demonstrate that monomers and dimers are the only independent oligomeric states encountered. Indeed, circular dichroism and fluorescence spectroscopies showed that Trp/Tyr residues participate in homodimerization and that the dimer is less thermostable than the monomer. A homodimer three-dimensional model was constructed and indicates that Trp147/Tyr137 are at the homodimer interface. Spectroscopy results validated the 3D-model and assigned 85° to the disulfide bridge dihedral angle responsible for dimerization. The homodimer model suggests that alterations in the membrane/carbohydrate-binding sites in one of the monomers, as result of dimerization, could explain the decrease in the homodimer ability to form pores.
A compendium of long non-coding RNAs transcriptional fingerprint in multiple myeloma
Authors: Ronchetti Domenica , Agnelli Luca , Pietrelli Alessandro , Todoerti Katia , Manzoni Martina , Taiana Elisa , Neri Antonino 
Published: April 2018

AbstractMultiple myeloma (MM) is a clonal proliferation of bone marrow plasma cells characterized by highly heterogeneous genetic background and clinical course, whose pathogenesis remains largely unknown. Long ncRNAs (lncRNAs) are a large class of non-protein-coding RNA, involved in many physiological cellular and genomic processes as well as in carcinogenesis and tumor evolution. Although still in its infancy, the role of lncRNAs in MM is progressively expanding. Besides studies on selected candidates, lncRNAs expression at genome-wide transcriptome level is confined to microarray technologies, thus investigating a limited collection of transcripts. In the present study investigating a cohort of 30 MM patients, a deep RNA-sequencing analysis overwhelmed previous array studies and allowed the most accurate definition of lncRNA transcripts structure and expression, ultimately providing a comprehensive catalogue of lncRNAs specifically associated with the main MM molecular subgroups and genetic alterations. Despite the small number of analyzed samples, the high accuracy of RNA-sequencing approach for complex transcriptome processing led to the identification of 391 deregulated lncRNAs, 67% of which were also detectable and validated by whole-transcript microarrays. In addition, we identified a list of lncRNAs, with potential relevance in MM, co-expressed and in close proximity to genes that might undergo a cis-regulatory relationship.
Identification of the allosteric P2X7 receptor antagonist [11C]SMW139 as a PET tracer of microglial activation
Authors: Janssen Bieneke , Vugts Danielle J. , Wilkinson Shane M. , Ory Dieter , Chalon Sylvie , Hoozemans Jeroen J. M. , Schuit Robert C. , Beaino Wissam , Kooijman Esther J. M. , van den Hoek Johan , Chishty Mansoor , Doméné Aurélie , Van der Perren Anke , Villa Alessandro , Maggi Adriana , Molenaar Ger T. , Funke Uta , Shevchenko Rostislav V. , Baekelandt Veerle , Bormans Guy , Lammertsma Adriaan A. , Kassiou Michael , Windhorst Albert D. 
Published: April 2018

AbstractThe P2X7 receptor plays a significant role in microglial activation, and as a potential drug target, the P2X7 receptor is also an interesting target in positron emission tomography. The current study aimed at the development and evaluation of a potent tracer targeting the P2X7 receptor, to which end four adamantanyl benzamide analogues with high affinity for the human P2X7 receptor were labelled with carbon-11. All four analogues could be obtained in excellent radiochemical yield and high radiochemical purity and molar activity, and all analogues entered the rat brain. [11C]SMW139 showed the highest metabolic stability in rat plasma, and showed high binding to the hP2X7 receptor in vivo in a hP2X7 receptor overexpressing rat model. Although no significant difference in binding of [11C]SMW139 was observed between post mortem brain tissue of Alzheimer’s disease patients and that of healthy controls in in vitro autoradiography experiments, [11C]SMW139 could be a promising tracer for P2X7 receptor imaging using positron emission tomography, due to high receptor binding in vivo in the hP2X7 receptor overexpressing rat model. However, further investigation of both P2X7 receptor expression and binding of [11C]SMW139 in other neurological diseases involving microglial activation is warranted.