bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bitter tastants and artificial sweeteners activate a subset of epithelial cells in acute tissue slices of the rat trachea
Authors: Lasconi Chiara , Pifferi Simone , Hernandez-Clavijo Andres , Merigo Flavia , Cecchini Maria Paola , Gonzalez-Velandia Kevin Y. , Agostinelli Emilio , Sbarbati Andrea , Menini Anna 
Published: June 2019

AbstractBitter and sweet receptors (T2Rs and T1Rs) are expressed in many extra-oral tissues including upper and lower airways. To investigate if bitter tastants and artificial sweeteners could activate physiological responses in tracheal epithelial cells we performed confocal Ca2+ imaging recordings on acute tracheal slices. We stimulated the cells with denatonium benzoate, a T2R agonist, and with the artificial sweeteners sucralose, saccharin and acesulfame-K. To test cell viability we measured responses to ATP. We found that 39% of the epithelial cells responding to ATP also responded to bitter stimulation with denatonium benzoate. Moreover, artificial sweeteners activated different percentages of the cells, ranging from 5% for sucralose to 26% for saccharin, and 27% for acesulfame-K. By using carbenoxolone, a gap junction blocker, we excluded that responses were mainly mediated by Ca2+ waves through cell-to-cell junctions. Pharmacological experiments showed that both denatonium and artificial sweeteners induced a PLC-mediated release of Ca2+ from internal stores. In addition, bitter tastants and artificial sweeteners activated a partially overlapping subpopulation of tracheal epithelial cells. Our results provide new evidence that a subset of ATP-responsive tracheal epithelial cells from rat are activated by both bitter tastants and artificial sweeteners.
Proteomic profiling of extracellular vesicles reveals additional diagnostic biomarkers for myocardial infarction compared to plasma alone
Authors: Gidlöf Olof , Evander Mikael , Rezeli Melinda , Marko-Varga György , Laurell Thomas , Erlinge David 
Published: June 2019

AbstractExtracellular vesicles (EVs) are submicron, membrane-enclosed particles that are released from cells in various pathophysiological states. The molecular cargo of these vesicles is considered to reflect the composition of the cell of origin, and the EV proteome is therefore a potential source of biomarkers for various diseases. Our aim was to determine whether EVs isolated from plasma provide additional diagnostic value or improved pathophysiological understanding compared to plasma alone in the context of myocardial infarction (MI). A panel of proximity extension assays (n = 92) was employed to analyze EV lysates and plasma from patients with MI (n = 60) and healthy controls (n = 22). After adjustment for multiple comparisons, a total of 11 dysregulated proteins were identified in EVs of MI patients compared to the controls (q < 0.01). Three of these proteins: chymotrypsin C (CTRC), proto-oncogene tyrosine-protein kinase SRC (SRC) and C-C motif chemokine ligand 17 (CCL17) were unaltered in the corresponding plasma samples. As biomarkers for MI, rudimentary to no evidence exists for these proteins. In a separate group of patients with varying degrees of coronary artery disease, the decrease in EV-associated (but not plasma-related) SRC levels was confirmed by ELISA. Confirmation of the presence of SRC on EVs of different sizes and cellular origins was performed with ELISA, flow cytometry and nanoparticle tracking analysis. In conclusion, the data revealed that despite a similarity in the EV and plasma proteomes, analysis of isolated EVs does indeed provide additional diagnostic information that cannot be obtained from plasma alone.
The future of coffee and cocoa agroforestry in a warmer Mesoamerica
Authors: de Sousa Kauê , van Zonneveld Maarten , Holmgren Milena , Kindt Roeland , Ordoñez Jenny C. 
Published: June 2019

AbstractClimate change threatens coffee production and the livelihoods of thousands of families in Mesoamerica that depend on it. Replacing coffee with cocoa and integrating trees in combined agroforestry systems to ameliorate abiotic stress are among the proposed alternatives to overcome this challenge. These two alternatives do not consider the vulnerability of cocoa and tree species commonly used in agroforestry plantations to future climate conditions. We assessed the suitability of these alternatives by identifying the potential changes in the distribution of coffee, cocoa and the 100 most common agroforestry trees found in Mesoamerica. Here we show that cocoa could potentially become an alternative in most of coffee vulnerable areas. Agroforestry with currently preferred tree species is highly vulnerable to future climate change. Transforming agroforestry systems by changing tree species composition may be the best approach to adapt most of the coffee and cocoa production areas. Our results stress the urgency for land use planning considering climate change effects and to assess new combinations of agroforestry species in coffee and cocoa plantations in Mesoamerica.
Adiponectin improves long-term potentiation in the 5XFAD mouse brain
Authors: Wang Ming , Jo Jihoon , Song Juhyun 
Published: June 2019

AbstractAdiponectin is an adipokine that regulates apoptosis, glucose and lipid metabolism, and insulin sensitivity in metabolic diseases. As recent studies have associated changes in adipokines and other metabolites in the central nervous system with a risk for Alzheimer’s disease (AD), we investigated the effects of adiponectin treatment on hippocampal cells in the 5XFAD mouse model of AD and neuronal SH-SY5Y cells under amyloid beta toxicity. Adiponectin treatment reduced levels of cleaved caspase 3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) apoptosis signalling and decreased glycogen synthase kinase 3 beta (GSK3β) activation. Moreover, adiponectin treatment triggered long-term potentiation in the hippocampi of 5XFAD mice, which was associated with reduced expression of N-methyl-d-aspartate and its receptor as well as surface expression of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that adiponectin inhibits neuronal apoptosis and inflammatory mechanisms and promotes hippocampal long-term potentiation. Thus, adiponectin exhibits beneficial effect on hippocampal synaptic plasticity in Alzheimer’s disease mouse model.
Generation of fully functional hepatocyte-like organoids from human induced pluripotent stem cells mixed with Endothelial Cells
Authors: Pettinato Giuseppe , Lehoux Sylvain , Ramanathan Rajesh , Salem Mohamed M. , He Li-Xia , Muse Oluwatoyosi , Flaumenhaft Robert , Thompson Melissa T. , Rouse Emily A. , Cummings Richard D. , Wen Xuejun , Fisher Robert A. 
Published: June 2019

AbstractDespite advances in stem cell research, cell transplantation therapy for liver failure is impeded by a shortage of human primary hepatocytes (HPH), along with current differentiation protocol limitations. Several studies have examined the concept of co-culture of human induced pluripotent cells (hiPSCs) with various types of supporting non-parenchymal cells to attain a higher differentiation yield and to improve hepatocyte-like cell functions both in vitro and in vivo. Co-culturing hiPSCs with human endothelial cells (hECs) is a relatively new technique that requires more detailed studies. Using our 3D human embryoid bodies (hEBs) formation technology, we interlaced Human Adipose Microvascular Endothelial Cells (HAMEC) with hiPSCs, leading to a higher differentiation yield and notable improvements across a wide range of hepatic functions. We conducted a comprehensive gene and protein secretion analysis of our HLCs coagulation factors profile, showing promising results in comparison with HPH. Furthermore, a stage-specific glycomic analysis revealed that the differentiated hepatocyte-like clusters (HLCs) resemble the glycan features of a mature tissue rather than cells in culture. We tested our HLCs in animal models, where the presence of HAMEC in the clusters showed a consistently better performance compared to the hiPSCs only group in regard to persistent albumin secretion post-transplantation.
Experimental Observation of Linear and Rotational Doppler Shifts from Several Designer Surfaces
Authors: Liu Baiyang , Chu Hongchen , Giddens Henry , Li Ronglin , Hao Yang 
Published: June 2019

AbstractAn orbital angular momentum (OAM) carrying beam has the ability to detect a spinning surface from its rotational Doppler effect. However, a mixture of linear and rotational Doppler effects can occur when an OAM beam is illuminated to a target, with not only spins but also vibrations. In this paper, we experimentally observe using OAM carrying beams, both linear and rotational Doppler effects from several designer surfaces. Specifically, a spinning polarization-independent metasurface, helicoidal reflector and propeller are applied respectively in this study. We demonstrate by the use of two microwave beams with opposite OAM to separate rotational Doppler shift from micro-Doppler shift. The proposed method can also be applied to measure the spinning speed of rotational objects, which have wider applications in intelligent sensing, radar and quantum optics.
Cardiovascular alterations in rats with Parkinsonism induced by 6-OHDA and treated with Domperidone
Authors: Rodrigues Laís D. , Oliveira Leandro F. , Shinoda Lucas , Scorza Carla A. , Faber Jean , Ferraz Henrique B. , Britto Luiz R. G. , Scorza Fulvio A. 
Published: June 2019

AbstractAfter Alzheimer, Parkinson disease (PD) is the most frequently occurring progressive, degenerative neurological disease. It affects both sympathetic and parasympathetic nervous systems in a variable fashion. Cardiovascular symptoms are present in almost all stages of PD and narrower heart rate variability is the earliest sign. Administration of Levodopa to PD patients has proven to provide some degree of neurological protection. This drug, however, causes side effects including nausea and vomiting, lessened by the administration of domperidone. Autopsies in PD patients led some researchers to suggest the involvement of the ventricular arrhythmia induced by domperidone. The aim of the present study was to determine the impact of the adjusted human maximal dose of domperidone, on cardiological features of Wistar rats. domperidone was administered to both 6-hydroxydopamine Parkinsonism models and regular Wistar rats. Quantitative analysis of ranges of heart beat variation showed significant abnormal distribution in both groups receiving domperidone as compared with respective sham counterparts. However, qualitative analysis of Poincaré plots showed that 6-hydroxydopamine Parkinsonism models receiving domperidone had the narrowest full range of heart beat and the worst distribution heart beat ranges as compared with all study groups corroborating with previous suggestion that domperidone administration to PD patients is likely to play a role in sudden unexpected death in this group of patients.
Screening DNA-targeted anticancer drug in vitro based on cancer cells DNA-templated silver nanoclusters
Authors: Zhang Feng , Sheng Hao , Wang Shuang , Ma Yu , Cai Changqun 
Published: June 2019

AbstractA reliable and sensitive cancer cells DNA-templated silver nanoclusters probe has been proposed for screening DNA-targeted anticancer drugs in vitro. In this paper, the DNA-templated silver nanoclusters was used to investigate the binding between anthracycline antibiotics and DNA. The template of DNA-templated silver nanoclusters was extracted from human liver carcinoma cells directly, which can express the drug activities against cancer cells more direct than the normal cells DNA. The anti-tumor activities of the four drugs were validated by MTT and apoptotic assay as Mitoxantrone > Epirubicin > Daunorubicin > Adriamycin.
Sleep-like slow oscillations improve visual classification through synaptic homeostasis and memory association in a thalamo-cortical model
Authors: Capone Cristiano , Pastorelli Elena , Golosio Bruno , Paolucci Pier Stanislao 
Published: June 2019

AbstractThe occurrence of sleep passed through the evolutionary sieve and is widespread in animal species. Sleep is known to be beneficial to cognitive and mnemonic tasks, while chronic sleep deprivation is detrimental. Despite the importance of the phenomenon, a complete understanding of its functions and underlying mechanisms is still lacking. In this paper, we show interesting effects of deep-sleep-like slow oscillation activity on a simplified thalamo-cortical model which is trained to encode, retrieve and classify images of handwritten digits. During slow oscillations, spike-timing-dependent-plasticity (STDP) produces a differential homeostatic process. It is characterized by both a specific unsupervised enhancement of connections among groups of neurons associated to instances of the same class (digit) and a simultaneous down-regulation of stronger synapses created by the training. This hierarchical organization of post-sleep internal representations favours higher performances in retrieval and classification tasks. The mechanism is based on the interaction between top-down cortico-thalamic predictions and bottom-up thalamo-cortical projections during deep-sleep-like slow oscillations. Indeed, when learned patterns are replayed during sleep, cortico-thalamo-cortical connections favour the activation of other neurons coding for similar thalamic inputs, promoting their association. Such mechanism hints at possible applications to artificial learning systems.
Energy absorption in the laser-QED regime
Authors: Savin Alex F. , Ross Aimee J. , Aboushelbaya Ramy , Mayr Marko W. , Spiers Ben , Wang Robin H.-W. , Norreys Peter A. 
Published: June 2019

AbstractA theoretical and numerical investigation of non-ponderomotive absorption at laser intensities relevant to quantum electrodynamics is presented. It is predicted that there is a regime change in the dependence of fast electron energy on incident laser energy that coincides with the onset of pair production via the Breit-Wheeler process. This prediction is numerically verified via an extensive campaign of QED-inclusive particle-in-cell simulations. The dramatic nature of the power law shift leads to the conclusion that this process is a candidate for an unambiguous signature that future experiments on multi-petawatt laser facilities have truly entered the QED regime.
Delayed development of the protective IL-17A response following a Giardia muris infection in neonatal mice
Authors: Paerewijck Oonagh , Maertens Brecht , Gagnaire Aurélie , De Bosscher Karolien , Geldhof Peter 
Published: June 2019

AbstractGiardia is an intestinal protozoan parasite that has the ability to infect a wide range of hosts, which can result in the clinical condition ‘giardiasis’. Over the years, experimental research has shown the crucial involvement of IL-17A to steer the protective immune response against Giardia. The development of the protective response, as reflected by a significant drop in cyst secretion, typically takes around 3 to 4 weeks. However, early-life infections often have a more chronic character lasting for several weeks or months. Therefore, the aim of the current study was to investigate the dynamics of a Giardia muris infection and the subsequent host immune response in neonatal mice infected 4 days after birth. The outcome of the study showed that a G. muris infection in pre-weaned mice failed to trigger a protective IL-17A response, which could explain the prolonged course of infection in comparison to older mice. Only after weaning, a protective intestinal immune response started to develop, characterized by an upregulation of IL-17A and Mbl2 and the secretion of parasite-specific IgA.
Improving the electrochemical performances using a V-doped Ni-rich NCM cathode
Authors: Sim Seoung-Ju , Lee Seung-Hwan , Jin Bong-Soo , Kim Hyun-Soo 
Published: June 2019

AbstractNi-rich layered LiNi0.84Co0.10Mn0.06O2 cathode material was modified by doping with vanadium to enhance the electrochemical performances. The XRD, FESEM and XPS analyses were indicated that the vanadium is successfully doped in the crystal lattice of LiNi0.84Co0.10Mn0.06O2 with high crystallinity. 0.05 mol% vanadium doped LiNi0.84Co0.10Mn0.06O2 exhibits superior initial discharge capacity of 204.4 mAh g−1, cycling retention of 88.1% after 80 cycles and rate capability of 86.2% at 2 C compared to those of pristine sample. It can be inferred that the vanadium doping can stabilize the crystal structure and improve the lithium-ion kinetics of the layered cathode materials.
Comparison of the Clinical Sensitivity of the Idylla Platform and the OncoBEAM RAS CRC Assay for KRAS Mutation Detection in Liquid Biopsy Samples
Authors: Vivancos Ana , Aranda Enrique , Benavides Manuel , Élez Elena , Gómez-España Maria Auxiliadora , Toledano Marta , Alvarez Martina , Parrado Maria Rosario Chica , García-Barberán Vanesa , Diaz-Rubio Eduardo 
Published: June 2019

AbstractKRAS mutations are common in colorectal cancer (CRC). In this setting, mutation status determination in circulating-free DNA from blood samples (liquid biopsy) has been shown to be a viable alternative to tissue testing. The objective of this study was to compare the sensitivity of two liquid biopsy methods for detecting KRAS mutations in plasma samples from metastatic CRC patients. Samples with a positive (KRAS-MUT+) result and a mutant allelic fraction (MAF) < 5% according to the OncoBEAM RAS CRC assay were pairly analyzed by the Idylla ctKRAS Mutation Test (n = 116). In a cohort of 71 patients with at least 1 year of follow-up, the progression-free survival (PFS) was determined according to MAF values. Idylla detected KRAS mutations in 81/116 OncoBEAM KRAS-MUT+ samples with MAF < 5% and in 48/79 samples with MAF < 1%. Concordance between OncoBEAM and Idylla significantly improved at higher MAF values. PFS rates at 6 and 12 months tended to be lower in patients with MAF levels between 1% and 5% than in those with levels <1%. OncoBEAM demonstrated greater sensitivity for plasma detection of KRAS mutations than Idylla. Importantly, our data identified a “gray zone” below 1% MAF where Idylla showed reduced KRAS mutation detection, highlighting the importance of an accurate method to provide the mutational status of CRC patients.
Adopting machine learning to automatically identify candidate patients for corneal refractive surgery
Authors: Yoo Tae Keun , Ryu Ik Hee , Lee Geunyoung , Kim Youngnam , Kim Jin Kuk , Lee In Sik , Kim Jung Sub , Rim Tyler Hyungtaek 
Published: June 2019

AbstractRecently, it has become more important to screen candidates that undergo corneal refractive surgery to prevent complications. Until now, there is still no definitive screening method to confront the possibility of a misdiagnosis. We evaluate the possibilities of machine learning as a clinical decision support to determine the suitability to corneal refractive surgery. A machine learning architecture was built with the aim of identifying candidates combining the large multi-instrument data from patients and clinical decisions of highly experienced experts. Five heterogeneous algorithms were used to predict candidates for surgery. Subsequently, an ensemble classifier was developed to improve the performance. Training (10,561 subjects) and internal validation (2640 subjects) were conducted using subjects who had visited between 2016 and 2017. External validation (5279 subjects) was performed using subjects who had visited in 2018. The best model, i.e., the ensemble classifier, had a high prediction performance with the area under the receiver operating characteristic curves of 0.983 (95% CI, 0.977–0.987) and 0.972 (95% CI, 0.967–0.976) when tested in the internal and external validation set, respectively. The machine learning models were statistically superior to classic methods including the percentage of tissue ablated and the Randleman ectatic score. Our model was able to correctly reclassify a patient with postoperative ectasia as an ectasia-risk group. Machine learning algorithms using a wide range of preoperative information achieved a comparable performance to screen candidates for corneal refractive surgery. An automated machine learning analysis of preoperative data can provide a safe and reliable clinical decision for refractive surgery.
ATP binds and inhibits the neurodegeneration-associated fibrillization of the FUS RRM domain
Authors: Kang Jian , Lim Liangzhong , Song Jianxing 
Published: June 2019

AbstractAdenosine triphosphate (ATP) provides energy for cellular processes but has recently been found to act also as a hydrotrope to maintain protein homeostasis. ATP bivalently binds the disordered domain of FUS containing the RG/RGG sequence motif and thereby affects FUS liquid-liquid phase separation. Here, using NMR spectroscopy and molecular docking studies, we report that ATP specifically binds also to the well-folded RRM domain of FUS at physiologically relevant concentrations and with the binding interface overlapping with that of its physiological ssDNA ligand. Importantly, although ATP has little effect on the thermodynamic stability of the RRM domain or its binding to ssDNA, ATP kinetically inhibits the RRM fibrillization that is critical for the gain of cytotoxicity associated with ALS and FTD. Our study provides a previously unappreciated mechanism for ATP to inhibit fibrillization by specific binding, and suggests that ATP may bind additional proteins other than the classic ATP-dependent enzymes.
Membrane curvature induces cardiolipin sorting
Authors: Beltrán-Heredia Elena , Tsai Feng-Ching , Salinas-Almaguer Samuel , Cao Francisco J. , Bassereau Patricia , Monroy Francisco 
Published: June 2019

AbstractCardiolipin is a cone-shaped lipid predominantly localized in curved membrane sites of bacteria and in the mitochondrial cristae. This specific localization has been argued to be geometry-driven, since the CL’s conical shape relaxes curvature frustration. Although previous evidence suggests a coupling between CL concentration and membrane shape in vivo, no precise experimental data are available for curvature-based CL sorting in vitro. Here, we test this hypothesis in experiments that isolate the effects of membrane curvature in lipid-bilayer nanotubes. CL sorting is observed with increasing tube curvature, reaching a maximum at optimal CL concentrations, a fact compatible with self-associative clustering. Observations are compatible with a model of membrane elasticity including van der Waals entropy, from which a negative intrinsic curvature of −1.1 nm−1 is predicted for CL. The results contribute to understanding the physicochemical interplay between membrane curvature and composition, providing key insights into mitochondrial and bacterial membrane organization and dynamics.
Plastoquinone homoeostasis by Arabidopsis proton gradient regulation 6 is essential for photosynthetic efficiency
Authors: Pralon Thibaut , Shanmugabalaji Venkatasalam , Longoni Paolo , Glauser Gaetan , Ksas Brigitte , Collombat Joy , Desmeules Saskia , Havaux Michel , Finazzi Giovanni , Kessler Felix 
Published: June 2019

AbstractPhotosynthesis produces organic carbon via a light-driven electron flow from H2O to CO2 that passes through a pool of plastoquinone molecules. These molecules are either present in the photosynthetic thylakoid membranes, participating in photochemistry (photoactive pool), or stored (non-photoactive pool) in thylakoid-attached lipid droplets, the plastoglobules. The photoactive pool acts also as a signal of photosynthetic activity allowing the adaptation to changes in light condition. Here we show that, in Arabidopsis thaliana, proton gradient regulation 6 (PGR6), a predicted atypical kinase located at plastoglobules, is required for plastoquinone homoeostasis, i.e. to maintain the photoactive plastoquinone pool. In a pgr6 mutant, the photoactive pool is depleted and becomes limiting under high light, affecting short-term acclimation and photosynthetic efficiency. In the long term, pgr6 seedlings fail to adapt to high light and develop a conditional variegated leaf phenotype. Therefore, PGR6 activity, by regulating plastoquinone homoeostasis, is required to cope with high light.