bluuebunny/crossref_metadata_2025_split huggingface dataset:
Durability of cell line xenograft resection models to interrogate tumor micro-environment targeting agents
Authors: Miller Ian S. , Shiels Liam P. , Conroy Emer , Connor Kate , Dicker Patrick , Gallagher William M. , Donovan Norma O’ , Kerbel Robert S. , Crown John , Byrne Annette T. 
Published: June 2019

AbstractAngiogenesis is a key tumor microenvironment (TME) event underpinning tumor growth and metastasis. Nevertheless, the relatively poor performance of anti-angiogenic therapies in clinical trials compared to pre-clinical studies implies that classical subcutaneous xenograft models have limited predictive potential in this setting. To address this issue, we established orthotopic surgical resection models of breast cancer, which replicate the phenotype of clinical post-resection micro-metastasis. To demonstrate the power and precision of these models, we recapitulated the BETH adjuvant trial (NCT00625898) where the addition of bevacizumab (BVZ) to chemotherapy plus trastuzumab (Trast) failed to provide additional benefit. SCID mice were orthotopically implanted with bioluminescent Her2+ MDA-MB-231 or HCC1954 cells and tumors resected c.5 weeks later. Following resection, mice were treated with 10 mg/kg Trast +5 mg/kg paclitaxel (PAC) IP once weekly for 6 cycles +/− weekly BVZ (5 mg/kg IP). Metastasis was monitored by imaging. Using these models our data confirms that the addition of the anti-angiogenic antibody BVZ to adjuvant Trast + chemotherapy provides no additional benefit compared with Trast + chemotherapy alone. Previous studies using non-resection subcutaneously engrafted xenografts failed to predict this outcome. Our results provide compelling evidence for the utility of cell line xenograft resection models to predict clinical outcome for TME targeting agents.
Environment mediated multipartite and multidimensional entanglement
Authors: Lee Chee Kong , Najafabadi Mojdeh S. , Schumayer Daniel , Kwek Leong Chuan , Hutchinson David A. W. 
Published: June 2019

AbstractQuantum entanglement is usually considered a fragile quantity and decoherence through coupling to an external environment, such as a thermal reservoir, can quickly destroy the entanglement resource. This doesn't have to be the case and the environment can be engineered to assist in the formation of entanglement. We investigate a system of qubits and higher dimensional spins interacting only through their mutual coupling to a reservoir. We explore the entanglement of multipartite and multidimensional system as mediated by the bath and show that at low temperatures and intermediate coupling strengths multipartite entanglement may form between qubits and between higher spins, i.e., qudits. We characterise the multipartite entanglement using an entanglement witness based upon the structure factor and demonstrate its validity versus the directly calculated entanglement of formation, suggesting possible experiments for its measure.
QSAR Classification Models for Predicting the Activity of Inhibitors of Beta-Secretase (BACE1) Associated with Alzheimer’s Disease
Authors: Ponzoni Ignacio , Sebastián-Pérez Víctor , Martínez María J. , Roca Carlos , De la Cruz Pérez Carlos , Cravero Fiorella , Vazquez Gustavo E. , Páez Juan A. , Díaz Mónica F. , Campillo Nuria E. 
Published: June 2019

AbstractAlzheimer’s disease is one of the most common neurodegenerative disorders in elder population. Theβ-site amyloid cleavage enzyme 1 (BACE1) is the major constituent of amyloid plaques and plays a central role in this brain pathogenesis, thus it constitutes an auspicious pharmacological target for its treatment. In this paper, a QSAR model for identification of potential inhibitors of BACE1 protein is designed by using classification methods. For building this model, a database with 215 molecules collected from different sources has been assembled. This dataset contains diverse compounds with different scaffolds and physical-chemical properties, covering a wide chemical space in the drug-like range. The most distinctive aspect of the applied QSAR strategy is the combination of hybridization with backward elimination of models, which contributes to improve the quality of the final QSAR model. Another relevant step is the visual analysis of the molecular descriptors that allows guaranteeing the absence of information redundancy in the model. The QSAR model performances have been assessed by traditional metrics, and the final proposed model has low cardinality, and reaches a high percentage of chemical compounds correctly classified.
Loss of MafA and MafB expression promotes islet inflammation
Authors: Singh Tania , Colberg Jesper K. , Sarmiento Luis , Chaves Patricia , Hansen Lisbeth , Bsharat Sara , Cataldo Luis R. , Dudenhöffer-Pfeifer Monika , Fex Malin , Bryder David , Holmberg Dan , Sitnicka Ewa , Cilio Corrado , Prasad Rashmi B. , Artner Isabella 
Published: June 2019

AbstractMaf transcription factors are critical regulators of beta-cell function. We have previously shown that reduced MafA expression in human and mouse islets is associated with a pro-inflammatory gene signature. Here, we investigate if the loss of Maf transcription factors induced autoimmune processes in the pancreas. Transcriptomics analysis showed expression of pro-inflammatory as well as immune cell marker genes. However, clusters of CD4+ T and B220+ B cells were associated primarily with adult MafA−/−MafB+/−, but not MafA−/− islets. MafA expression was detected in the thymus, lymph nodes and bone marrow suggesting a novel role of MafA in regulating immune-cell function. Analysis of pancreatic lymph node cells showed activation of CD4+ T cells, but lack of CD8+ T cell activation which also coincided with an enrichment of naïve CD8+ T cells. Further analysis of T cell marker genes revealed a reduction of T cell receptor signaling gene expression in CD8, but not in CD4+ T cells, which was accompanied with a defect in early T cell receptor signaling in mutant CD8+ T cells. These results suggest that loss of MafA impairs both beta- and T cell function affecting the balance of peripheral immune responses against islet autoantigens, resulting in local inflammation in pancreatic islets.
Augmentation of spinal cord glutamatergic synaptic currents in zebrafish primary motoneurons expressing mutant human TARDBP (TDP-43)
Authors: Petel Légaré Virginie , Harji Ziyaan A. , Rampal Christian J. , Allard-Chamard Xavier , Rodríguez Esteban C. , Armstrong Gary A. B. 
Published: June 2019

AbstractThough there is compelling evidence that de-innervation of neuromuscular junctions (NMJ) occurs early in amyotrophic lateral sclerosis (ALS), defects arising at synapses in the spinal cord remain incompletely understood. To investigate spinal cord synaptic dysfunction, we took advantage of a zebrafish larval model and expressed either wild type human TARDBP (wtTARDBP) or the ALS-causing G348C variant (mutTARDBP). The larval zebrafish is ideally suited to examine synaptic connectivity between descending populations of neurons and spinal cord motoneurons as a fully intact spinal cord is preserved during experimentation. Here we provide evidence that the tail-beat motor pattern is reduced in both frequency and duration in larvae expressing mutTARDBP. In addition, we report that motor-related synaptic depolarizations in primary motoneurons of the spinal cord are shorter in duration and fewer action potentials are evoked in larvae expressing mutTARDBP. To more thoroughly examine spinal cord synaptic dysfunction in our ALS model, we isolated AMPA/kainate-mediated glutamatergic miniature excitatory post-synaptic currents in primary motoneurons and found that in addition to displaying a larger amplitude, the frequency of quantal events was higher in larvae expressing mutTARDBP when compared to larvae expressing wtTARDBP. In a final series of experiments, we optogenetically drove neuronal activity in the hindbrain and spinal cord population of descending ipsilateral glutamatergic interneurons (expressing Chx10) using the Gal4-UAS system and found that larvae expressing mutTARDBP displayed abnormal tail-beat patterns in response to optogenetic stimuli and augmented synaptic connectivity with motoneurons. These findings indicate that expression of mutTARDBP results in functionally altered glutamatergic synapses in the spinal cord.
Highly-ordered Triptycene Modifier Layer Based on Blade Coating for Ultraflexible Organic Transistors
Authors: Kondo Masaya , Kajitani Takashi , Uemura Takafumi , Noda Yuki , Ishiwari Fumitaka , Shoji Yoshiaki , Araki Teppei , Yoshimoto Shusuke , Fukushima Takanori , Sekitani Tsuyoshi 
Published: June 2019

AbstractWe present a highly ordered surface modification layer for polymers based on ambient solution-processed triptycene (Trip) derivatives for high-mobility organic thin-film transistors (OTFTs). The nested packing of Trip molecules results in the formation of 2D hexagonal arrays, which stack one-dimensionally on the surface of polymer dielectrics without anchoring groups. The Trip surface was previously shown to be preferable for the growth of organic semiconductors (OSCs), and hence for enhancing the mobility of OTFTs. However, although the Trip modifier layer has been realized by thermal evaporation in a high-vacuum environment (TVE), it still has grain-boundary disorders that hinder the optimal growth of OSCs. To fabricate OTFTs with higher mobility, a disorder-free Trip layer is needed. We developed highly ordered Trip layers on polymer dielectrics via blade coating. In addition, we clarified that the highly ordered Trip modifier layer enhances the mobility of the OTFTs by more than 40%, relative to the disordered Trip layer prepared by TVE. Finally, we realized a ring oscillator composed of OTFTs with a highly ordered Trip layer.
Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes
Authors: Lussier Yoann , Fürst Oliver , Fortea Eva , Leclerc Marc , Priolo Dimitri , Moeller Lena , Bichet Daniel G. , Blunck Rikard , D’Avanzo Nazzareno 
Published: June 2019

AbstractThe four hyperpolarization-activated cylic-nucleotide gated (HCN) channel isoforms and their auxiliary subunit KCNE2 are important in the regulation of peripheral and central neuronal firing and the heartbeat. Disruption of their normal function has been implicated in cardiac arrhythmias, peripheral pain, and epilepsy. However, molecular details of the HCN-KCNE2 complexes are unknown. Using single-molecule subunit counting, we determined that the number of KCNE2 subunits in complex with the pore-forming subunits of human HCN channels differs with each HCN isoform and is dynamic with respect to concentration. These interactions can be altered by KCNE2 gene-variants with functional implications. The results provide an additional consideration necessary to understand heart rhythm, pain, and epileptic disorders.
The duration of the interpregnancy interval in multiparous women and maternal weight gain between pregnancies: findings from a UK population-based cohort
Authors: Ziauddeen Nida , Roderick Paul J. , Macklon Nicholas S. , Alwan Nisreen A. 
Published: June 2019

AbstractMaternal obesity in pregnancy increases the risk of adverse long-term health outcomes in both mother and offspring. A population-based cohort of prospectively collected routine antenatal healthcare data collected between January 2003 and September 2017 at University Hospital Southampton, UK was utilised to investigate the association between duration of interpregnancy interval between successive pregnancies and gain in maternal body mass index by the start of the next pregnancy. Records of 19362 women with two or more consecutive singleton live births were analysed. Two-thirds had gained weight when presenting to antenatal care for their subsequent pregnancy with 20% becoming overweight/obese. Compared to an interval of 24–35 months, an interval of 12–23 months was associated with lowest risk of weight gain (adjusted RR 0.91, 99% CI 0.87 to 0.95, p < 0.001) and ≥36 months with greatest risk (adjusted RR 1.11, 99% CI 1.07 to 1.15, p < 0.001) for the first to second pregnancy. This study shows that most multiparous women start their pregnancy with a higher weight than their previous one. An interval of 12–23 months is associated with the lowest risk of starting the second pregnancy with a higher body weight accounting for age. In countries with high prevalence of maternal obesity, birth spacing may merit exploration as a factor impacting on perinatal morbidity.
Healthy adiposity and extended lifespan in obese mice fed a diet supplemented with a polyphenol-rich plant extract
Authors: Aires Virginie , Labbé Jérôme , Deckert Valérie , Pais de Barros Jean-Paul , Boidot Romain , Haumont Marc , Maquart Guillaume , Le Guern Naig , Masson David , Prost-Camus Emmanuelle , Prost Michel , Lagrost Laurent 
Published: June 2019

AbstractObesity may not be consistently associated with metabolic disorders and mortality later in life, prompting exploration of the challenging concept of healthy obesity. Here, the consumption of a high-fat/high-sucrose (HF/HS) diet produces hyperglycaemia and hypercholesterolaemia, increases oxidative stress, increases endotoxaemia, expands adipose tissue (with enlarged adipocytes, enhanced macrophage infiltration and the accumulation of cholesterol and oxysterols), and reduces the median lifespan of obese mice. Despite the persistence of obesity, supplementation with a polyphenol-rich plant extract (PRPE) improves plasma lipid levels and endotoxaemia, prevents macrophage recruitment to adipose tissues, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends the median lifespan. PRPE drives the normalization of the HF/HS-mediated functional enrichment of genes associated with immunity and inflammation (in particular the response to lipopolysaccharides). The long-term limitation of immune cell infiltration in adipose tissue by PRPE increases the lifespan through a mechanism independent of body weight and fat storage and constitutes the hallmark of a healthy adiposity trait.
RETRACTED ARTICLE: Gut Microbiota Alteration is Characterized by a Proteobacteria and Fusobacteria Bloom in Kwashiorkor and a Bacteroidetes Paucity in Marasmus
Authors: Pham Thi-Phuong-Thao , Tidjani Alou Maryam , Bachar Dipankar , Levasseur Anthony , Brah Souleymane , Alhousseini Daouda , Sokhna Cheikh , Diallo Aldiouma , Wieringa Frank , Million Matthieu , Raoult Didier 
Published: June 2019

AbstractKwashiorkor and marasmus are considered to be two different clinical diseases resulting from severe malnutrition, but this distinction has been questioned. In a previous study comparing children with kwashiorkor and healthy children from Niger and Senegal, we found a dramatic gut microbiota alteration with a predominant depletion of anaerobes and enrichment in Proteobacteria and Fusobacteria in kwashiorkor. However, it remained unknown whether this association was related to malnutrition or was a specific feature of kwashiorkor. In this continuation study, we added 7 new marasmus subjects and 71,162 new colonies from the same countries. Our results showed that, compared to marasmus, the kwashiorkor gut microbiota was characterized by an increased proportion of Proteobacteria (culturomics, Marasmus 5.0%, Kwashiorkor 16.7%, p < 0.0001; metagenomics, Marasmus 14.7%, Kwashiorkor 22.0%, p = 0.001), but there was a decreased proportion of Bacteroidetes in marasmus (culturomics, Marasmus 0.8%, Kwashiorkor 6.5%, p = 0.001; metagenomics, Marasmus 5.4%, Kwashiorkor 7.0%, p = 0.03). Fusobacterium was more frequently cultured from kwashiorkor. All detected potential pathogenic species were enriched in the kwashiorkor gut microbiota. These results provide a biological basis to support the usage of an antibiotic therapy more effective in suppressing the overgrowth of bacterial communities resistant to penicillin, combined with antioxidants and probiotics for nutritional recovery therapies, particularly for kwashiorkor.
An untargeted fecal and urine metabolomics analysis of the interplay between the gut microbiome, diet and human metabolism in Indian and Chinese adults
Authors: Jain Abhishek , Li Xin Hui , Chen Wei Ning 
Published: June 2019

AbstractGut microbiome plays a vital role in human health. Human fecal and urine metabolome could provide a functional readout of gut microbial metabolism as well as its interaction with host and diet. However, this relationship still needs to be fully characterized. We established an untargeted GC-MS metabolomics method which enabled the detection of 122 and 86 metabolites including amino acids, phenolics, indoles, carbohydrates, sugars and metabolites of microbial origin from fecal and urine samples respectively. 41 compounds were confirmed using external standards. Next, we compared the fecal and urine metabolome of 16 healthy Indian and Chinese adults, ages 22–35 years, using a combined GC-MS and LC-MS approach. We showed dietary habit or ethnicity wise grouping of urine and fecal metabolite profiles of Indian and Chinese adults. Our analysis revealed 53 differentiating metabolites including higher abundance of amino acids and phenolics in Chinese and higher abundance of fatty acids, glycocholic acid, metabolites related to tryptophan metabolism in Indian adults. Correlation analysis showed a strong association of metabolites with gut bacterial profiles of the same subjects in the genus and species level. Thus, our results suggest that gut bacterial compositional changes could be eventually monitored and probed using a metabolomics approach.
Anaplasma phagocytophilum modifies tick cell microRNA expression and upregulates isc-mir-79 to facilitate infection by targeting the Roundabout protein 2 pathway
Authors: Artigas-Jerónimo Sara , Alberdi Pilar , Villar Rayo Margarita , Cabezas-Cruz Alejandro , Prados Pedro J. Espinosa , Mateos-Hernández Lourdes , de la Fuente José 
Published: June 2019

AbstractThe microRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms including innate and adaptive immune pathways to control bacterial, parasite and viral infections, and pathogens could modify host miRNA profile to facilitate infection and multiplication. Therefore, understanding the function of host miRNAs in response to pathogen infection is relevant to characterize host-pathogen molecular interactions and to provide new targets for effective new interventions for the control infectious diseases. The objective of this study was to characterize the dynamics and functional significance of the miRNA response of the tick vector Ixodes scapularis in response to Anaplasma phagocytophilum infection, the causative agent of human and animal granulocytic anaplasmosis. To address this objective, the composition of tick miRNAs, functional annotation, and expression profiling was characterized using high throughout RNA sequencing in uninfected and A. phagocytophilum-infected I. scapularis ISE6 tick cells, a model for tick hemocytes involved in pathogen infection. The results provided new evidences on the role of tick miRNA during pathogen infection, and showed that A. phagocytophilum modifies I. scapularis tick cell miRNA profile and upregulates isc-mir-79 to facilitate infection by targeting the Roundabout protein 2 (Robo2) pathway. Furthermore, these results suggested new targets for interventions to control pathogen infection in ticks.
Characterization of irreversible electroporation on the stomach: A feasibility study in rats
Authors: Lee Jae Min , Choi Hyuk Soon , Kim Eun Sun , Keum Bora , Seo Yeon Seok , Jeen Yoon Tae , Lee Hong Sik , Chun Hoon Jai , Um Soon Ho , Kim Chang Duck , Kim Hong Bae 
Published: June 2019

AbstractIrreversible electroporation (IRE) is a newly developed non-thermal ablative therapy. During the IRE procedure, the permeability of the cell membrane is irreversibly changed by application of high-energy pulses across the tissue. This induces the breakdown of cell homeostasis, and thereby cell death. Here, we present an in vivo study to demonstrate IRE ablation of gastric tissue and characterize the changes that occur with time therein. No significant complications were observed in the test rats during the experiment. The electroporated tissues exhibited apoptosis at 10, 24 and 48 h after IRE ablation. The apoptosis peaked at 10 h after IRE and then declined, suggesting that the ablated tissue rapidly recovered owing to intense metabolic activity. In addition, the electroporated tissues exhibited morphological changes such as pyknosis and karyorrhexis, while histological analysis showed that the blood vessels were preserved. Interestingly, electroporation greatly affected the mucosa and muscularis propria, but not the submucosa and serosa. This study suggests that IRE could potentially be used as a minimally invasive treatment for early gastric cancer that does not exhibit lymph node metastasis or dysplasia.
A connectivity-based parcellation improved functional representation of the human cerebellum
Authors: Ren Yudan , Guo Lei , Guo Christine Cong 
Published: June 2019

AbstractThe cerebellum is traditionally well known for its role in motor learning and coordination. Recently, it is recognized that the function of the cerebellum is highly diverse and extends to non-motor domains, such as working memory, emotion and language. The diversity of the cerebellum can be appreciated by examining its extensive connectivity to the cerebral regions selective for both motor and cognitive functions. Importantly, the pattern of cerebro-cerebellar connectivity is specific and distinct to different cerebellar subregions. Therefore, to understand the cerebellum and the various functions it involves, it is essential to identify and differentiate its subdivisions. However, most studies are still referring the cerebellum as one brain structure or by its gross anatomical subdivisions, which does not necessarily reflect the functional mapping of the cerebellum. We here employed a data-driven method to generate a functional connectivity-based parcellation of the cerebellum. Our results demonstrated that functional connectivity-based atlas is superior to existing atlases in regards to cluster homogeneity, accuracy of functional connectivity representation and individual identification. Furthermore, our functional atlas improves statistical results of task fMRI analyses, as compared to the standard voxel-based approach and existing atlases. Our detailed functional parcellation provides a valuable tool for elucidating the functional diversity and connectivity of the cerebellum as well as its network relationships with the whole brain.
Features of diclofenac biodegradation by Rhodococcus ruber IEGM 346
Authors: Ivshina Irina B. , Tyumina Elena A. , Kuzmina Maria V. , Vikhareva Elena V. 
Published: June 2019

AbstractThis study investigated the ability of rhodococci to biodegrade diclofenac (DCF), one of the polycyclic non-steroidal anti-inflammatory drugs (NSAIDs) most frequently detected in the environment. Rhodococcus ruber strain IEGM 346 capable of complete DCF biodegradation (50 µg/L) over 6 days was selected. It is distinguished by the ability to degrade DCF at high (50 mg/L) concentrations unlike other known biodegraders. The DCF decomposition process was accelerated by adding glucose and due to short-term cell adaptation to 5 µg/L DCF. The most typical responses to DCF exposure observed were the changed ζ-potential of bacterial cells; increased cell hydrophobicity and total cell lipid content; multi-cellular conglomerates formed; and the changed surface-to-volume ratio. The obtained findings are considered as mechanisms of rhodococcal adaptation and hence their increased resistance to toxic effects of this pharmaceutical pollutant. The proposed pathways of bacterial DCF metabolisation were described. The data confirming the C-N bond cleavage and aromatic ring opening in the DCF structure were obtained.