bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Notch system during pubertal development of the bovine mammary gland
Authors: Bonadeo Nadia , Becu-Villalobos Damasia , Cristina Carolina , Lacau-Mengido Isabel M. 
Published: June 2019

AbstractThe development of the mammary gland of cows during pre-weaning and puberty will condition its future productive capacity and warrants special study. In this respect, Notch signaling regulates tissue development and fate by modifying cell proliferation and differentiation and has been involved in stem cell maintenance, but has not been extensively studied in the developing mammary glands in cows. We therefore investigated Notch receptor expression and localization, as well as the expression of Notch ligands and target genes in the mammary gland of Holstein heifers in pre- and post-pubertal stages. Notch receptors 1 to 4 were detected by immunohistochemistry in the parenchyma and stroma of the developing gland. The subcellular localization of the four receptors was predominantly cytoplasmic except for NOTCH4, which was mostly nuclear. The membrane and the active intracellular domains of NOTCH paralogues were identified by western blot. NOTCH1 and NOTCH2 active domains increased during pubertal stages while NOTCH3 and NOTCH4 active domains decreased, suggesting strikingly different involvement of NOTCH paralogues in bovine mammary gland development and differentiation. The mRNA expression levels of the target genes HEY1 and HEY2 increased during peri-puberty whereas no variation of HES1 mRNA levels was observed. The mRNA levels of the Notch ligands JAGGED1 and DELTA1 also increased gradually during development. In conclusion, Notch signaling system dynamically varies throughout the development of the mammary gland during puberty pointing to specific time involvement of each component.
Altered intrinsic brain activity associated with outcome in frontal lobe epilepsy
Authors: Wu Xintong , Liu Wenyu , Wang Weina , Gao Hui , Hao Nanya , Yue Qiang , Gong Qiyong , Zhou Dong 
Published: June 2019

AbstractFrontal lobe epilepsy (FLE) is the second most common type of the focal epilepsies. Our understanding of this disease has been revolutionized over the past decade, but variable treatment outcomes persist and the underlying functional mechanisms responsible for this have yet to be deciphered. This study was designed to determine how intrinsic brain connectivity related to treatment response in patients with FLE. 50 patients with FLE and 28 healthy controls were enrolled in this study and underwent functional MRI at baseline. At the end of 12-month follow up period, all patients with FLE were classified, based on their responses to AEDs treatment, into drug-responsive and drug-refractory groups. The amplitude of low-frequency fluctuation (ALFF) was calculated amongst the three groups in order to detect regional neural function integration. The responsive group showed decreased ALFF only in the left ventromedial prefrontal cortex (vmPFC), while the refractory group showed decreased ALFF in the left vmPFC, right superior frontal gyrus (SFG), and supramarginal gyrus (SMG) relative to healthy controls. In addition, both the responsive and refractory groups showed increased ALFF in the precuneus and postcentral gyrus when compared to the healthy controls. Furthermore, the refractory group exhibited significantly decreased ALFF in the left vmPFC, right SFG and SMG, relative to the responsive group. Focal spontaneous activity, as assessed by ALFF, was associated with response to antiepileptic treatment in patients with FLE. Patients with refractory frontal lobe epilepsy exhibited decreased intrinsic brain activity. Our findings provide novel neuroimaging evidence into the mechanisms of medically-intractable FLE at the brain level.
The levels of the NMDA receptor co-agonist D-serine are reduced in the substantia nigra of MPTP-lesioned macaques and in the cerebrospinal fluid of Parkinson’s disease patients
Authors: Nuzzo Tommaso , Punzo Daniela , Devoto Paola , Rosini Elena , Paciotti Silvia , Sacchi Silvia , Li Qin , Thiolat Marie-Laure , Véga Celine , Carella Massimo , Carta Manolo , Gardoni Fabrizio , Calabresi Paolo , Pollegioni Loredano , Bezard Erwan , Parnetti Lucilla , Errico Francesco , Usiello Alessandro 
Published: June 2019

AbstractDysfunction of NMDA receptor (NMDAR)-mediated transmission is supposed to contribute to the motor and non-motor symptoms of Parkinson’s Disease (PD), and to L-DOPA-induced dyskinesia. Besides the main agonist L-glutamate, two other amino acids in the atypical D-configuration, D-serine and D-aspartate, activate NMDARs. In the present work, we investigated the effect of dopamine depletion on D-amino acids metabolism in the brain of MPTP-lesioned Macaca mulatta, and in the serum and cerebrospinal fluid of PD patients. We found that MPTP treatment increases D-aspartate and D-serine in the monkey putamen while L-DOPA rescues both D-amino acids levels. Conversely, dopaminergic denervation is associated with selective D-serine reduction in the substantia nigra. Such decrease suggests that the beneficial effect of D-serine adjuvant therapy previously reported in PD patients may derive from the normalization of endogenous D-serine levels and consequent improvement of nigrostriatal hypoglutamatergic transmission at glycine binding site. We also found reduced D-serine concentration in the cerebrospinal fluid of L-DOPA-free PD patients. These results further confirm the existence of deep interaction between dopaminergic and glutamatergic neurotransmission in PD and disclose a possible direct influence of D-amino acids variations in the changes of NMDAR transmission occurring under dopamine denervation and L-DOPA therapy.
Colourimetric analysis of thermally altered human bone samples
Authors: Krap Tristan , Ruijter Jan M. , Nota Kevin , Karel Joyce , Burgers A. Lieke , Aalders Maurice C. G. , Oostra Roelof-Jan , Duijst Wilma 
Published: June 2019

AbstractAt this moment, no method is available to objectively estimate the temperature to which skeletal remains have been exposed during a fire. Estimating this temperature can provide crucial information in a legal investigation. Exposure of bone to heat results in observable and measurable changes, including a change in colour. To determine the exposure temperature of experimental bone samples, heat related changes in colour were systemically studied by means of image analysis. In total 1138 samples of fresh human long bone diaphysis and epiphysis, varying in size, were subjected to heat ranging from room temperature to 900 °C for various durations and in different media. The samples were scanned with a calibrated flatbed scanner and photographed with a Digital Single Lens Reflex camera. Red, Green, Blue values and Lightness, A-, and B-coordinates were collected for statistical analysis. Cluster analysis showed that discriminating thresholds for Lightness and B-coordinate could be defined and used to construct a model of decision rules. This model enables the user to differentiate between seven different temperature clusters with relatively high precision and accuracy. The proposed decision model provides an objective, robust and non-destructive method for estimating the exposure temperature of heated bone samples.
A genetically encoded fluorescent temperature sensor derived from the photoactive Orange Carotenoid Protein
Authors: Maksimov Eugene G. , Yaroshevich Igor A. , Tsoraev Georgy V. , Sluchanko Nikolai N. , Slutskaya Ekaterina A. , Shamborant Olga G. , Bobik Tatiana V. , Friedrich Thomas , Stepanov Alexey V. 
Published: June 2019

AbstractThe heterogeneity of metabolic reactions leads to a non-uniform distribution of temperature in different parts of the living cell. The demand to study normal functioning and pathological abnormalities of cellular processes requires the development of new visualization methods. Previously, we have shown that the 35-kDa photoswitchable Orange Carotenoid Protein (OCP) has a strong temperature dependency of photoconversion rates, and its tertiary structure undergoes significant structural rearrangements upon photoactivation, which makes this protein a nano-sized temperature sensor. However, the determination of OCP conversion rates requires measurements of carotenoid absorption, which is not suitable for microscopy. In order to solve this problem, we fused green and red fluorescent proteins (TagGFP and TagRFP) to the structure of OCP, producing photoactive chimeras. In such chimeras, electronic excitation of the fluorescent protein is effectively quenched by the carotenoid in OCP. Photoactivation of OCP-based chimeras triggers rearrangements of complex geometry, permitting measurements of the conversion rates by monitoring changes of fluorescence intensity. This approach allowed us to determine the local temperature of the microenvironment. Future directions to improve the OCP-based sensor are discussed.
Excision and transfer of an integrating and conjugative element in a bacterial species with high recombination efficiency
Authors: Weiss Evelyn , Spicher Carolin , Haas Rainer , Fischer Wolfgang 
Published: June 2019

AbstractHorizontal transfer of mobile genetic elements, such as integrating and conjugative elements (ICEs), plays an important role in generating diversity and maintaining comprehensive pan-genomes in bacterial populations. The human gastric pathogen Helicobacter pylori, which is known for its extreme genetic diversity, possesses highly efficient transformation and recombination systems to achieve this diversity, but it is unclear to what extent these systems influence ICE physiology. In this study, we have examined the excision/integration and horizontal transfer characteristics of an ICE (termed ICEHptfs4) in these bacteria. We show that transfer of ICEHptfs4 DNA during mating between donor and recipient strains is independent of its conjugation genes, and that homologous recombination is much more efficient than site-specific integration into the recipient chromosome. Nevertheless, ICEHptfs4 excision by site-specific recombination occurs permanently in a subpopulation of cells and involves relocation of a circularization-dependent promoter. Selection experiments for excision indicate that the circular form of ICEHptfs4 is not replicative, but readily reintegrates by site-specific recombination. Thus, although ICEHptfs4 harbours all essential transfer genes, and typical ICE functions such as site-specific integration are active in H. pylori, canonical ICE transfer is subordinate to the more efficient general DNA uptake and homologous recombination machineries in these bacteria.
Epoxidation Kinetics of High-Linolenic Triglyceride Catalyzed by Solid Acidic-Ion Exchange Resin
Authors: Kousaalya Adhimoolam Bakthavachalam , Beyene Shiferaw D. , Ayalew Beshah , Pilla Srikanth 
Published: June 2019

AbstractEpoxidation of high-linolenic perilla oil was carried out in the presence of solid acidic ion-exchange resin at varying reaction temperatures for 8 h. A pseudo two-phase kinetic model that captures the differences in reactivity of double bonds at various positions in the fatty acid of a triglyceride molecule during both epoxy formation and cleavage was developed. The proposed model is based on the Langmuir-Hinshelwood-Hougen-Watson (L-H-H-W) postulates and considers the adsorption of formic acid on the catalyst as the rate-determining step. To estimate the kinetic rate constants of various reactions, genetic algorithm was used to fit experimentally obtained iodine and epoxy values of epoxidized perilla oil. A re-parametrized form of Arrhenius equation was used in the proposed model to facilitate the precise estimation of parameters with least computational effort. The obtainment of the least error between experimentally determined and theoretically predicted iodine and epoxy values indicates the robustness of the proposed model.
Nitric oxide and ROS mediate autophagy and regulate Alternaria alternata toxin-induced cell death in tobacco BY-2 cells
Authors: Sadhu Abhishek , Moriyasu Yuji , Acharya Krishnendu , Bandyopadhyay Maumita 
Published: June 2019

AbstractSynergistic interaction of nitric oxide (NO) and reactive oxygen species (ROS) is essential to initiate cell death mechanisms in plants. Though autophagy is salient in either restricting or promoting hypersensitivity response (HR)-related cell death, the crosstalk between the reactive intermediates and autophagy during hypersensitivity response is paradoxical. In this investigation, the consequences of Alternaria alternata toxin (AaT) in tobacco BY-2 cells were examined. At 3 h, AaT perturbed intracellular ROS homeostasis, altered antioxidant enzyme activities, triggered mitochondrial depolarization and induced autophagy. Suppression of autophagy by 3-Methyladenine caused a decline in cell viability in AaT treated cells, which indicated the vital role of autophagy in cell survival. After 24 h, AaT facilitated Ca2+ influx with an accumulation of reactive oxidant intermediates and NO, to manifest necrotic cell death. Inhibition of NO accumulation by 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) decreased the level of necrotic cell death, and induced autophagy, which suggests NO accumulation represses autophagy and facilitates necrotic cell death at 24 h. Application of N-acetyl-L-cysteine at 3 h, confirmed ROS to be the key initiator of autophagy, and together with cPTIO for 24 h, revealed the combined effects of NO and ROS is required for necrotic HR cell death.
High-energy, high-resolution, fly-scan X-ray phase tomography
Authors: Wang Hongchang , Atwood Robert C. , Pankhurst Matthew James , Kashyap Yogesh , Cai Biao , Zhou Tunhe , Lee Peter David , Drakopoulos Michael , Sawhney Kawal 
Published: June 2019

AbstractHigh energy X-ray phase contrast tomography is tremendously beneficial to the study of thick and dense materials with poor attenuation contrast. Recently, the X-ray speckle-based imaging technique has attracted widespread interest because multimodal contrast images can now be retrieved simultaneously using an inexpensive wavefront modulator and a less stringent experimental setup. However, it is time-consuming to perform high resolution phase tomography with the conventional step-scan mode because the accumulated time overhead severely limits the speed of data acquisition for each projection. Although phase information can be extracted from a single speckle image, the spatial resolution is deteriorated due to the use of a large correlation window to track the speckle displacement. Here we report a fast data acquisition strategy utilising a fly-scan mode for near field X-ray speckle-based phase tomography. Compared to the existing step-scan scheme, the data acquisition time can be significantly reduced by more than one order of magnitude without compromising spatial resolution. Furthermore, we have extended the proposed speckle-based fly-scan phase tomography into the previously challenging high X-ray energy region (120 keV). This development opens up opportunities for a wide range of applications where exposure time and radiation dose are critical.
Do you understand the words that are comin outta my mouth? Voice assistant comprehension of medication names
Authors: Palanica Adam , Thommandram Anirudh , Lee Andrew , Li Michael , Fossat Yan 
Published: June 2019

AbstractThis study investigated the speech recognition abilities of popular voice assistants when being verbally asked about commonly dispensed medications by a variety of participants. Voice recordings of 46 participants (12 of which had a foreign accent in English) were played back to Amazon’s Alexa, Google Assistant, and Apple’s Siri for the brand- and generic names of the top 50 most dispensed medications in the United States. A repeated measures ANOVA indicated that Google Assistant achieved the highest comprehension accuracy for both brand medication names (M = 91.8%, SD = 4.2) and generic medication names (M = 84.3%, SD = 11.2), followed by Siri (brand names M = 58.5%, SD = 11.2; generic names M = 51.2%, SD = 16.0), and the lowest accuracy by Alexa (brand names M = 54.6%, SD = 10.8; generic names M = 45.5%, SD = 15.4). An interaction between voice assistant and participant accent was also found, demonstrating lower comprehension performance overall for those with a foreign accent using Siri (M = 48.8%, SD = 11.8) and Alexa (M = 41.7%, SD = 12.7), compared to participants without a foreign accent (Siri M = 57.0%, SD = 11.7; Alexa M = 53.0%, SD = 10.9). No significant difference between participant accents were found for Google Assistant. These findings show a substantial performance lead for Google Assistant compared to its voice assistant competitors when comprehending medication names, but there is still room for improvement.
GECKO is a genetic algorithm to classify and explore high throughput sequencing data
Authors: Thomas Aubin , Barriere Sylvain , Broseus Lucile , Brooke Julie , Lorenzi Claudio , Villemin Jean-Philippe , Beurier Gregory , Sabatier Robert , Reynes Christelle , Mancheron Alban , Ritchie William 
Published: June 2019

AbstractComparative analysis of high throughput sequencing data between multiple conditions often involves mapping of sequencing reads to a reference and downstream bioinformatics analyses. Both of these steps may introduce heavy bias and potential data loss. This is especially true in studies where patient transcriptomes or genomes may vary from their references, such as in cancer. Here we describe a novel approach and associated software that makes use of advances in genetic algorithms and feature selection to comprehensively explore massive volumes of sequencing data to classify and discover new sequences of interest without a mapping step and without intensive use of specialized bioinformatics pipelines. We demonstrate that our approach called GECKO for GEnetic Classification using k-mer Optimization is effective at classifying and extracting meaningful sequences from multiple types of sequencing approaches including mRNA, microRNA, and DNA methylome data.
Thermococcus sp. 9°N DNA polymerase exhibits 3′-esterase activity that can be harnessed for DNA sequencing
Authors: LinWu Shiuan-Woei , Tu Yu-Hsuan , Tsai Ting-Yueh , Maestre-Reyna Manuel , Liu Mu-Sen , Wu Wen-Jin , Huang Jyun-Yuan , Chi Hung-Wen , Chang Wei-Hsin , Chiou Chung-Fan , Wang Andrew H.-J. , Lee Johnsee , Tsai Ming-Daw 
Published: June 2019

AbstractIt was reported in 1995 that T7 and Taq DNA polymerases possess 3′-esterase activity, but without follow-up studies. Here we report that the 3′-esterase activity is intrinsic to the Thermococcus sp. 9°N DNA polymerase, and that it can be developed into a continuous method for DNA sequencing with dNTP analogs carrying a 3′-ester with a fluorophore. We first show that 3′-esterified dNTP can be incorporated into a template-primer DNA, and solve the crystal structures of the reaction intermediates and products. Then we show that the reaction can occur continuously, modulated by active site residues Tyr409 and Asp542. Finally, we use 5′-FAM-labeled primer and esterified dNTP with a dye to show that the reaction can proceed to ca. 450 base pairs, and that the intermediates of many individual steps can be identified. The results demonstrate the feasibility of a 3′-editing based DNA sequencing method that could find practical applications after further optimization.
Enhanced photo-sensitivity in a Si photodetector using a near-field assisted excitation
Authors: Yatsui T. , Okada S. , Takemori T. , Sato T. , Saichi K. , Ogamoto T. , Chiashi S. , Maruyama S. , Noda M. , Yabana K. , Iida K. , Nobusada K. 
Published: June 2019

AbstractSilicon is an indispensable material in electric device technology. However, Si is an indirect bandgap material; therefore, its excitation efficiency, which requires phonon assistance, is low under propagating far-field light. To improve the excitation efficiency, herein we performed optical near-field excitation, which is confined in a nano-scale, where the interband transitions between different wave numbers are excited according to the uncertainty principle; thus, optical near-field can directly excite the carrier in the indirect bandgap. To evaluate the effect of optical near-field confined in a nano-scale, we fabricate the lateral Si p–n junction with Au nanoparticles as sources to generate the field confinement. We observed a 47.0% increase in the photo-sensitivity rate. In addition, by using the thin lateral p–n junction, which eliminates the far-field excitation, we confirmed a 42.3% increase in the photo-sensitivity rate.
Establishment of a non-small-cell lung cancer-liver metastasis patient-derived tumor xenograft model for the evaluation of patient-tailored chemotherapy
Authors: Yang Xue , Meng Gaopei 
Published: June 2019

Abstract
In order to optimize patient-tailored chemotherapy, a non-small-cell lung cancer (NSCLC)-liver metastasis patient-derived tumor xenograft (PDTX) model is developed. Computed tomography (CT)-guided NSCLC percutaneous biopsy was subcutaneously inoculated into the flank of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice (PDTX F1) and allowed to reach 500 mm3 volume. Then, the tumors were re-transplanted into Balb/c nude mice and liver metastasis was confirmed (PDTX F2), which were further assigned into doxorubicin (DOX), docetaxel (DTX), and non-treatment control group. H&E staining and Keratin 20 (CK20) staining were applied to determine the consistency of PDTX models and primary tumors. Tumor growth curve, body weight, and the expression of p65 nuclear factor (NF)-κB and the secretion of interferon (IFN)-γ were investigated. The successive transplant procedure can induce the NSCLC-liver metastasis PDTX model, and morphological and structural characteristics of PDTX models (F2) were in accordance with primary tumors. DOX and DTX could delay tumor growth, activate the NF-κB pathway, and promote IFN-γ secretion in the PDTX models. The NSCLC-liver metastasis PDTX model is established and provides a powerful mean to assess chemotherapeutic efficacy.
MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway
Authors: Huang Zhengping , Xing Shan , Liu Meng , Deng Weiming , Wang Yunqing , Huang Zhixiang , Huang Yukai , Huang Xuechan , Wu Chiwei , Guo Xin , Pan Xia , Jiang Jiawei , Feng Fan , Li Tianwang 
Published: June 2019

Abstract
Behavior alterations in fibroblast-like synoviocytes (FLS) contribute to a pivotal role in pathogenesis of rheumatoid arthritis (RA). MiRNAs are closely involved in a variety of pathologic conditions. In the present study, we aimed to screen for the aberrant expression of miRNAs in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) to further identify the altered expression of miR-26a-5p in RA-FLS and to investigate the role of miR-26a-5p in RA. The altered expression of miR-26a-5p in RA-FLS was screened by microarray analysis and confirmed by quantitative real time PCR. The effect of miR-26a-5p on proliferation, cell cycle, apoptosis, and invasion in RA-FLS were studied. The verification of miR-26a-5p target mRNA and downstream signaling pathway was elucidated by bioinformatics analysis, dual luciferase reporter assay, and western blot. Expression of miR-26a-5p was higher in RA-FLS than in fibroblast-like synoviocytes from osteoarthritis patients and trauma patients. Overexpression of miR-26a-5p RA-FLS promoted cells proliferation, G1/S transition, cells invasion, and resisted apoptosis in RA-FLS, whereas it led to contrary effects when inhibiting the expression of miR-26a-5p. The 3′UTR of tensin homolog (PTEN) was directly targetted by miR-26a-5p and activation of phosphoinositide 3-kinase (PI3K)/AKT pathway was observed when overexpression of miR-26a-5p. Our study suggested that miR-26a-5p has a complementary role in cells proliferation, invasion, and apoptosis of RA-FLS, which may be attributed to its activation effect on PI3K/AKT signaling pathway via targetting PTEN. MiR-26a-5p is likely to be a clinically helpful target for novel therapeutic strategies in RA.