bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network pharmacology modeling identifies synergistic Aurora B and ZAK interaction in triple-negative breast cancer
Authors: Tang Jing , Gautam Prson , Gupta Abhishekh , He Liye , Timonen Sanna , Akimov Yevhen , Wang Wenyu , Szwajda Agnieszka , Jaiswal Alok , Turei Denes , Yadav Bhagwan , Kankainen Matti , Saarela Jani , Saez-Rodriguez Julio , Wennerberg Krister , Aittokallio Tero 
Published: July 2019

AbstractCancer cells with heterogeneous mutation landscapes and extensive functional redundancy easily develop resistance to monotherapies by emerging activation of compensating or bypassing pathways. To achieve more effective and sustained clinical responses, synergistic interactions of multiple druggable targets that inhibit redundant cancer survival pathways are often required. Here, we report a systematic polypharmacology strategy to predict, test, and understand the selective drug combinations for MDA-MB-231 triple-negative breast cancer cells. We started by applying our network pharmacology model to predict synergistic drug combinations. Next, by utilizing kinome-wide drug-target profiles and gene expression data, we pinpointed a synergistic target interaction between Aurora B and ZAK kinase inhibition that led to enhanced growth inhibition and cytotoxicity, as validated by combinatorial siRNA, CRISPR/Cas9, and drug combination experiments. The mechanism of such a context-specific target interaction was elucidated using a dynamic simulation of MDA-MB-231 signaling network, suggesting a cross-talk between p53 and p38 pathways. Our results demonstrate the potential of polypharmacological modeling to systematically interrogate target interactions that may lead to clinically actionable and personalized treatment options.
High throughput development of TCR-mimic antibody that targets survivin-2B80-88/HLA-A*A24 and its application in a bispecific T-cell engager
Authors: Kurosawa Nobuyuki , Wakata Yuka , Ida Kenta , Midorikawa Aki , Isobe Masaharu 
Published: July 2019

AbstractIntracellular tumor-associated antigens are targeted by antibodies known as T-cell receptor mimic antibodies (TCRm-Abs), which recognize T-cell epitopes with better stabilities and higher affinities than T-cell receptors. However, TCRm-Abs have been proven difficult to produce using conventional techniques. Here, we developed TCRm-Abs that recognize the survivin-2B-derived nonamer peptide, AYACNTSTL (SV2B80-88), presented on HLA-A*24 (SV2B80-88/HLA-A*24) from immunized mice by using a fluorescence-activated cell sorting-based antigen-specific plasma cells isolation method combined with a high-throughput single-cell-based immunoglobulin-gene-cloning technology. This approach yielded a remarkable efficiency in generating candidate antibody clones that recognize SV2B80-88/HLA-A*24. The screening of the antibody clones for their affinity and ability to bind key amino-acid residues within the target peptide revealed that one clone, #21-3, specifically recognized SV2B80-88/HLA-A*24 on T2 cells. The specificity of #21-3 was further established through survivin-2B-positive tumor cell lines that exogenously or endogenously express HLA-A*24. A bispecific T-cell engager comprised of #21-3 and anti-CD3 showed specific cytotoxicity towards cells bearing SV2B80-88/HLA-A*24 by recruiting and activating T-cells in vitro. The efficient development of TCRm-Ab overcomes the limitations that hamper antibody-based immunotherapeutic approaches and enables the targeting of intracellular tumor-associated antigens.
Expression of small heat shock proteins in exosomes from patients with gynecologic cancers
Authors: Wyciszkiewicz Aleksandra , Kalinowska-Łyszczarz Alicja , Nowakowski Błażej , Kaźmierczak Kamila , Osztynowicz Krystyna , Michalak Sławomir 
Published: July 2019

AbstractSmall Heat shock proteins (sHsp) are a group of chaperone proteins. Under conditions of stress, the expression of sHsp is increased. Therefore, they are implicated in the pathogenesis of various autoimmune-mediated disorders and cancer. The purpose of this study was to analyze sHsp expression in exosomes from patients with gynecologic cancers and correlate these results with markers of cytotoxic immune response. The study group included patients with ovarian cancer, endometrial cancer, and patients with endometriosis. The levels of sHsps and cytotoxic markers were analyzed in serum, peritoneal fluid and exosomes using ELISA method. We found the highest levels of sHsp in exosomes from patients with ovarian cancer, but they were also elevated in patients with endometrial cancer and endometriosis. Moreover, we identified the presence of small Hsps in serum and peritoneal fluid in all study groups, but again the highest level was in patients with ovarian cancer. Small Hsps expression levels were positively correlated with markers of cytotoxic immune response.
In vitro and ex vivo evaluation of the biological performance of sclerosing foams
Authors: Bottaro Elisabetta , Paterson Jemma A. J. , Quercia Luciano , Zhang Xunli , Hill Martyn , Patel Venisha A. , Jones Stephen A. , Lewis Andrew L. , Millar Timothy M. , Carugo Dario 
Published: July 2019

AbstractSince the first reports on foam sclerotherapy, multiple studies have been conducted to determine the physical properties and behavior of foams, but relatively little is known about their biological effects on the endothelial cells lining the vessel wall. Moreover, a systematic comparison of the biological performance of foams produced with different methods has not been carried out yet. Herein, a 2D in vitro method was developed to compare efficacy of commercially available polidocanol injectable foam (PEM, Varithena) and physician-compounded foams (PCFs). Endothelial cell attachment upon treatment with foam was quantified as an indicator of therapeutic efficacy, and was correlated with foam physical characteristics and administration conditions. An ex vivo method was also developed to establish the disruption and permeabilisation of the endothelium caused by sclerosing agents. It relied on the quantitation of extravasated bovine serum albumin conjugated to Evans Blue, as an indicator of endothelial permeability. In our series of comparisons, PEM presented a greater overall efficacy compared to PCFs, across the different biological models, which was attributed to its drainage dynamics and gas formulation. This is consistent with earlier studies that indicated superior physical cohesiveness of PEM compared to PCFs.
In vivo ultrasound-switchable fluorescence imaging
Authors: Yao Tingfeng , Yu Shuai , Liu Yang , Yuan Baohong 
Published: July 2019

AbstractThe conventional fluorescence imaging has limited spatial resolution in centimeter-deep tissue because of the tissue’s high scattering property. Ultrasound-switchable fluorescence (USF) imaging, a new imaging technique, was recently proposed to realize high-resolution fluorescence imaging in centimeter-deep tissue. However, in vivo USF imaging has not been achieved so far because of the lack of stable near-infrared contrast agents in a biological environment and the lack of data about their biodistributions. In this study, for the first time, we achieved in vivo USF imaging successfully in mice with high resolution. USF imaging in porcine heart tissue and mouse breast tumor via local injections were studied and demonstrated. In vivo and ex vivo USF imaging of the mouse spleen via intravenous injections was also successfully achieved. The results showed that the USF contrast agent adopted in this study was very stable in a biological environment, and it was mainly accumulated into the spleen of the mice. By comparing the results of CT imaging and the results of USF imaging, the accuracy of USF imaging was proved.
Seafloor hydrothermal activity along mid-ocean ridge with strong melt supply: study from segment 27, southwest Indian ridge
Authors: Yue Xihe , Li Huaiming , Ren Jianye , Tao Chunhui , Zhou Jianping , Wang Yuan , Lü Xiaoxia 
Published: July 2019

AbstractContinuous tow investigations have shown that the present vent field inventory along fast to intermediate spreading ridges may be underestimated by at least 3–6 times, while the limited towed line investigations of venting sites along slow to ultra-slow spreading ridges make it impossible to determine their distribution. The Chinese Dayang cruise has conducted detailed towed line surveys of hydrothermal activity on segment 27 of the ultra-slow spreading southwest Indian ridge in 2015. The results have identified as many as 9 hydrothermal fields along 85-km-long segment, including one confirmed hydrothermal field, three inferred hydrothermal fields and five suspected fields. Hydrothermal activities are not only limited along-axis but also found approximately 10 km away from the axis. These vent fields are likely powered by a seismically identified axial magma chamber, including melt migration along normal faults to flank areas. The calculated hydrothermal activity frequency on segment 27 is approximately 3.6–8 times higher than that calculated from the Interridge database, suggesting that careful system exploration can reveal more hydrothermal activities even on ultra-slow spreading ridges effected by hotspot.
Polyvinylidene fluoride/sulfonated graphene oxide blend membrane coated with polypyrrole/platinum electrode for ionic polymer metal composite actuator applications
Authors: Inamuddin  , Abbas Kashmery Heba 
Published: July 2019

AbstractA polyvinylidene fluoride, sulfonated graphene oxide composite membrane coated with polypyrrole (Ppy) and platinum metal (Pt) was fabricated. The Fourier-transform infrared (FTIR) spectroscopic analysis was done to analyze the functional groups present in the composite material. Deposition of PPy/Pt electrode and surface morphology of PVDF/SGO/Pt/PPy was confirmed by scanning electron microscopic (SEM) images. The capacity of ion exchange and proton conductivity (PC) of PVDF/SGO/Pt/PPy were 1.4 meq g−1 of dry ion exchanger and 4.251 × 10−2 S cm−1, respectively. A two-link flexible manipulator based on the fabricated ionic polymer metal composite (IPMC) membranes was also developed where the electromechanical behaviour of a polymer-based actuator provides an important step in robotics applications.
A Rationally Designed Humanized Antibody Selective for Amyloid Beta Oligomers in Alzheimer’s Disease
Authors: Gibbs Ebrima , Silverman Judith M. , Zhao Beibei , Peng Xubiao , Wang Jing , Wellington Cheryl L. , Mackenzie Ian R. , Plotkin Steven S. , Kaplan Johanne M. , Cashman Neil R. 
Published: July 2019

AbstractAdvances in the understanding of Alzheimer’s disease (AD) suggest that pathogenesis is not directly related to plaque burden, but rather to soluble toxic amyloid-beta oligomers (AßO). Therapeutic antibodies targeting Aß monomers and/or plaque have shown limited efficacy and dose-limiting adverse events in clinical trials. These findings suggest that antibodies capable of selectively neutralizing toxic AßO may achieve improved efficacy and safety. To this end, we generated monoclonal antibodies against a conformational Aß epitope predicted by computational modeling to be presented on toxic AßO but not monomers or fibrils. The resulting lead antibody, PMN310, showed the desired AßO-selective binding profile. In vitro, PMN310 inhibited AßO propagation and toxicity. In vivo, PMN310 prevented AßO-induced loss of memory formation and reduced synaptic loss and inflammation. A humanized version (huPMN310) compared favorably to other Aß-directed antibodies showing a lack of adverse event-associated binding to Aß deposits in AD brains, and greater selective binding to AßO-enriched AD brain fractions that contain synaptotoxic Aß species. Systemic administration of huPMN310 in mice resulted in brain exposure and kinetics comparable to those of other therapeutic human monoclonal antibodies. Greater selectivity for AßO and the potential to safely administer high doses of huPMN310 are expected to result in enhanced safety and therapeutic potency.
Geometric morphometrics for the study of facial expressions in non-human animals, using the domestic cat as an exemplar
Authors: Finka Lauren R. , Luna Stelio P. , Brondani Juliana T. , Tzimiropoulos Yorgos , McDonagh John , Farnworth Mark J. , Ruta Marcello , Mills Daniel S. 
Published: July 2019

AbstractFacial expression is a common channel for the communication of emotion. However, in the case of non-human animals, the analytical methods used to quantify facial expressions can be subjective, relying heavily on extrapolation from human-based systems. Here, we demonstrate how geometric morphometrics can be applied in order to overcome these problems. We used this approach to identify and quantify changes in facial shape associated with pain in a non-human animal species. Our method accommodates individual variability, species-specific facial anatomy, and postural effects. Facial images were captured at four different time points during ovariohysterectomy of domestic short haired cats (n = 29), with time points corresponding to varying intensities of pain. Images were annotated using landmarks specifically chosen for their relationship with underlying musculature, and relevance to cat-specific facial action units. Landmark data were subjected to normalisation before Principal Components (PCs) were extracted to identify key sources of facial shape variation, relative to pain intensity. A significant relationship between PC scores and a well-validated composite measure of post-operative pain in cats (UNESP-Botucatu MCPS tool) was evident, demonstrating good convergent validity between our geometric face model, and other metrics of pain detection. This study lays the foundation for the automatic, objective detection of emotional expressions in a range of non-human animal species.
Recovery of haemal lordosis in Gilthead seabream (Sparus aurata L.)
Authors: Fragkoulis Stefanos , Printzi Alice , Geladakis George , Katribouzas Nikos , Koumoundouros George 
Published: July 2019

AbstractHaemal lordosis is a frequent abnormality of the vertebral column. It has been recorded to develop in different finfish species, during the hatchery rearing phase. Under certain conditions, this abnormality reaches a high prevalence and severity degree, with significant effects on the external morphology of the fish. We show that haemal lordosis recovers during the on-growing of Gilthead seabream in sea cages. At the end of the hatchery phase, 1700 seabream juveniles were tagged electronically and examined for the presence of haemal lordosis. Subsequently, their morphology was examined periodically up to the end of the on-growing period. We found that the prevalence of fish with a lordotic external morphology decreased during the studied period by approximately 50%. Interestingly, 27% of the recovered fish presented a completely normal vertebral column. Geometric morphometric analysis showed no significant differences in the body shape between the fish with a recovered normal phenotype and the fish that were normal since the beginning of the on-growing period. Our results provide the first evidence for the recovery of lordosis during the growth of fish. A mechanism with multiple levels of remodeling of abnormal bones is suggested.
Investigations on the adhesion of new composites for restoring cervical lesions using energy dispersive X-ray analysis and scanning electron microscopy
Authors: Roman Alexandra , Stratul Stefan Ioan , Rusu Darian , Boariu Marius , Soanca Andrada , Balazsi Robert , Suciu Maria , Moldovan Mărioara , Bulboacă Adriana Elena 
Published: July 2019

AbstractRestoration of noncarious cervical lesions with resin composites is one of the treatment options, but the retention of the restorations located at the crown-root junction is still a cause of clinical concern. The aim of this study was to evaluate the adhesive properties of three experimental resin composites and two commercial materials used to restore cavities prepared on extracted teeth as well as to determine the relative elemental composition of these materials. We tested the null hypothesis, which considered that the adhesive behaviours of different resin composites did not differ. The microleakage test using tracers showed that all tested materials exhibited some degree of dentinal microleakage, although they all had good dentinal adhesion. The results failed to reject the null hypothesis. The scanning electron microscopy revealed completely adapted adhesive interfaces underneath the restorations along with well-developed hybrid layers depending on the adhesive system. Energy dispersive X-ray analysis analyses showed that the restorative materials have similar chemical compositions, with some differences between the samples from the same material. The results support the implementation of experimental resins in clinical settings.
Neural responses to action contingency error in different cortical areas are attributable to forward prediction or sensory processing
Authors: Kikuchi Tatsuo , Sugiura Motoaki , Yamamoto Yuki , Sasaki Yukako , Hanawa Sugiko , Sakuma Atsushi , Matsumoto Kazunori , Matsuoka Hiroo , Kawashima Ryuta 
Published: July 2019

AbstractThe contingency of sensory feedback to one’s actions is essential for the sense of agency, and experimental violation of this contingency is a standard paradigm in the neuroscience of self-awareness and schizophrenia. However, neural responses to this violation have arbitrarily been interpreted either as activation of the system generating forward prediction (agency-error account) or decreased suppression of processing of predictable input (prediction-error account). In this functional magnetic resonance imaging (fMRI) study, the regions responsive to auditory contingency errors were examined if they exhibited responses to an isolated auditory stimulus and to passive-contingency delay, which the prediction-error account expects. These responses were observed only in the auditory association cortex in the right superior temporal gyrus. Several multimodal and motor-association cortices did not exhibit these responses, suggesting their relevance to the agency-error account. Thus, we formulated the coexistence and dissociation of two accounts in neural contingency-error responses.
Multiple Pleomorphic Tetramers of Thermostable Direct Hemolysin from Grimontia hollisae in Exerting Hemolysis and Membrane Binding
Authors: Wang Yu-Kuo , Huang Sheng-Cih , Chang Chin-Yuan , Huang Wan-Ting , Liao Man-Jun , Yip Bak-Sau , Chou Feng-Pai , Li Thomas Tien-Hsiung , Wu Tung-Kung 
Published: July 2019

AbstractOligomerization of protein into specific quaternary structures plays important biological functions, including regulation of gene expression, enzymes activity, and cell–cell interactions. Here, we report the determination of two crystal structures of the Grimontia hollisae (formally described as Vibrio hollisae) thermostable direct hemolysin (Gh–TDH), a pore-forming toxin. The toxin crystalized in the same space group of P21212, but with two different crystal packing patterns, each revealing three consistent tetrameric oligomerization forms called Oligomer–I, –II, and –III. A central pore with comparable depth of ~50 Å but differing in shape and size was observed in all determined toxin tetrameric oligomers. A common motif of a toxin dimer was found in all determined structures, suggesting a plausible minimum functional unit within the tetrameric structure in cell membrane binding and possible hemolytic activity. Our results show that bacterial toxins may form a single or highly symmetric oligomerization state when exerting their biological functions. The dynamic nature of multiple symmetric oligomers formed upon release of the toxin may open a niche for bacteria survival in harsh living environments.
Monitoring of system conditioning after blank injections in untargeted UPLC-MS metabolomic analysis
Authors: Martínez-Sena Teresa , Luongo Giovanna , Sanjuan-Herráez Daniel , Castell José V. , Vento Máximo , Quintás Guillermo , Kuligowski Julia 
Published: July 2019

AbstractUltra-performance liquid chromatography – mass spectrometry (UPLC-MS) is widely used for untargeted metabolomics in biomedical research. To optimize the quality and precision of UPLC-MS metabolomic analysis, evaluation of blank samples for the elimination of background features is required. Although blanks are usually run either at the beginning or at the end of a sequence of samples, a systematic analysis of their effect of the instrument performance has not been properly documented. Using the analysis of two common bio-fluids (plasma and urine), we describe how the injection of blank samples within a sequence of samples may affect both the chromatographic and MS detection performance depending on several factors, including the sample matrix and the physicochemical properties of the metabolites of interest. The analysis of blanks and post-blank conditioning samples using t-tests, PCA and guided-PCA provides useful information for the elimination of background UPLC-MS features, the identification of column carry over and the selection of the number of samples required to achieve a stable performance.
Community analysis of gut microbiota in hornets, the largest eusocial wasps, Vespa mandarinia and V. simillima
Authors: Suenami Shota , Konishi Nobu Masaru , Miyazaki Ryo 
Published: July 2019

AbstractGut microbiota are important for various aspects of host physiology, and its composition is generally influenced by both intrinsic and extrinsic contexts of the host. Social bee gut microbiota composition is simple and highly stable hypothesized to be due to their unique food habit and social interactions. Here, we focused on hornets, the largest of the eusocial wasps – Vespa mandarinia and V. simillima. Unlike the well-studied honey bees, adult hornets are generally herbivorous but also hunt insects for broods, a unique behavior which could influence their gut microbiota. Analysis of the gut microbiome using 16S rRNA gene sequencing revealed that the two species have simple gut microbiota, composed of seven or eight consistently maintained ‘core’ operational taxonomic units (OTUs). While the two Vespa species shared some OTUs, the structures of their gut communities differed. Phylogenetic analysis indicated association of core OTUs with host diet. Intriguingly, prey honey bee gut microbes were detected in the V. simillima gut (and to a lesser extent in V. mandarinia), suggesting migration of microorganisms from the prey gut. This is the first report uncovering gut microbiome in hornets, giving additional insight into how food habit affects gut microbiota of social insects.