bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution and differential analysis of rat microglial markers in traumatic brain injury: conventional flow cytometric and bioinformatics analysis
Authors: Toledano Furman Naama , Gottlieb Assaf , Prabhakara Karthik S. , Bedi Supinder , Caplan Henry W. , Ruppert Katherine A. , Srivastava Amit K. , Olson Scott D. , Cox Charles S. 
Published: July 2020

AbstractTraumatic brain injury (TBI) results in a cascade of cellular responses, which produce neuroinflammation, partly due to microglial activation. Transforming from surveying to primed phenotypes, microglia undergo considerable molecular changes. However, specific microglial profiles in rat remain elusive due to tedious methodology and limited availability of reagents. Here, we present a flow cytometry-based analysis of rat microglia 24 h after TBI using the controlled cortical impact model, validated with a bioinformatics approach. Isolated microglia are analyzed for morphological changes and their expression of activation markers using flow cytometry, traditional gating-based analysis methods and support the data by employing bioinformatics statistical tools. We use CD45, CD11b/c, and p2y12 receptor to identify microglia and evaluate their activation state using CD32, CD86, RT1B, CD200R, and CD163. The results from logic-gated flow cytometry analysis was validated with bioinformatics-based analysis and machine learning algorithms to detect quantitative changes in morphology and marker expression in microglia due to activation following TBI.
Early detection of type 2 diabetes mellitus using machine learning-based prediction models
Authors: Kopitar Leon , Kocbek Primoz , Cilar Leona , Sheikh Aziz , Stiglic Gregor 
Published: July 2020

AbstractMost screening tests for T2DM in use today were developed using multivariate regression methods that are often further simplified to allow transformation into a scoring formula. The increasing volume of electronically collected data opened the opportunity to develop more complex, accurate prediction models that can be continuously updated using machine learning approaches. This study compares machine learning-based prediction models (i.e. Glmnet, RF, XGBoost, LightGBM) to commonly used regression models for prediction of undiagnosed T2DM. The performance in prediction of fasting plasma glucose level was measured using 100 bootstrap iterations in different subsets of data simulating new incoming data in 6-month batches. With 6 months of data available, simple regression model performed with the lowest average RMSE of 0.838, followed by RF (0.842), LightGBM (0.846), Glmnet (0.859) and XGBoost (0.881). When more data were added, Glmnet improved with the highest rate (+ 3.4%). The highest level of variable selection stability over time was observed with LightGBM models. Our results show no clinically relevant improvement when more sophisticated prediction models were used. Since higher stability of selected variables over time contributes to simpler interpretation of the models, interpretability and model calibration should also be considered in development of clinical prediction models.
A meta-analysis of multiple stressors on seagrasses in the context of marine spatial cumulative impacts assessment
Authors: Stockbridge Jackson , Jones Alice R. , Gillanders Bronwyn M. 
Published: July 2020

AbstractHumans are placing more strain on the world’s oceans than ever before. Furthermore, marine ecosystems are seldom subjected to single stressors, rather they are frequently exposed to multiple, concurrent stressors. When the combined effect of these stressors is calculated and mapped through cumulative impact assessments, it is often assumed that the effects are additive. However, there is increasing evidence that different combinations of stressors can have non-additive impacts, potentially leading to synergistic and unpredictable impacts on ecosystems. Accurately predicting how stressors interact is important in conservation, as removal of certain stressors could provide a greater benefit, or be more detrimental than would be predicted by an additive model. Here, we conduct a meta-analysis to assess the prevalence of additive, synergistic, and antagonistic stressor interaction effects using seagrasses as case study ecosystems. We found that additive interactions were the most commonly reported in seagrass studies. Synergistic and antagonistic interactions were also common, but there was no clear way of predicting where these non-additive interactions occurred. More studies which synthesise the results of stressor interactions are needed to be able to generalise interactions across ecosystem types, which can then be used to improve models for assessing cumulative impacts.
Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma
Authors: Simon Serrano Sonia , Sime Wondossen , Abassi Yasmin , Daams Renée , Massoumi Ramin , Jemaà Mohamed 
Published: July 2020

AbstractNeuroblastoma is the most common paediatric cancer type. Patients diagnosed with high-risk neuroblastoma have poor prognosis and occasionally tumours relapse. As a result, novel treatment strategies are needed for relapse and refractory neuroblastoma patients. Here, we found that high expression of Mps1 kinase (mitotic kinase Monopolar Spindle 1) was associated with relapse-free neuroblastoma patient outcomes and poor overall survival. Silencing and inhibition of Mps1 in neuroblastoma or PDX-derived cells promoted cell apoptosis via the caspase-dependent mitochondrial apoptotic pathway. The mechanism of cell death upon Mps1 inhibition was dependent on the polyploidization/aneuploidization of the cells before undergoing mitotic catastrophe. Furthermore, tumour growth retardation was confirmed in a xenograft mouse model after Mps1-inhibitor treatment. Altogether, these results suggest that Mps1 expression and inhibition can be considered as a novel prognostic marker as well as a therapeutic strategy for the treatment of high-risk neuroblastoma patients.
Structure and co-occurrence patterns of bacterial communities associated with white faeces disease outbreaks in Pacific white-leg shrimp Penaeus vannamei aquaculture
Authors: Alfiansah Yustian Rovi , Peters Sonja , Harder Jens , Hassenrück Christiane , Gärdes Astrid 
Published: July 2020

AbstractBacterial diseases cause production failures in shrimp aquacultures. To understand environmental conditions and bacterial community dynamics contributing to white faeces disease (WFD) events, we analysed water quality and compared bacterial communities in water as well as in intestines and faeces of healthy and diseased shrimps, respectively, via 16S rRNA gene sequencing and qPCR of transmembrane regulatory protein (toxR), thermolabile haemolysin (tlh), and thermostable direct haemolysin genes of pathogenic Vibrio parahaemolyticus as a proxy for virulence. WFD occurred when pH decreased to 7.71–7.84, and Alteromonas, Pseudoalteromonas and Vibrio dominated the aquatic bacterial communities. The disease severity further correlated with increased proportions of Alteromonas, Photobacterium, Pseudoalteromonas and Vibrio in shrimp faeces. These opportunistic pathogenic bacteria constituted up to 60% and 80% of the sequences in samples from the early and advances stages of the disease outbreak, respectively, and exhibited a high degree of co-occurrence. Furthermore, toxR and tlh were detected in water at the disease event only. Notably, bacterial community resilience in water occurred when pH was adjusted to 8. Then WFD ceased without a mortality event. In conclusion, pH was a reliable indicator of the WFD outbreak risk. Dissolved oxygen and compositions of water and intestinal bacteria may also serve as indicators for better prevention of WFD events.
Activation of cerebellum and basal ganglia during the observation and execution of manipulative actions
Authors: Errante Antonino , Fogassi Leonardo 
Published: July 2020

AbstractStudies on action observation mostly described the activation of a network of cortical areas, while less investigation focused specifically on the activation and role of subcortical nodes. In the present fMRI study, we investigated the recruitment of cerebellum and basal ganglia during the execution and observation of object manipulation performed with the right hand. The observation conditions consisted in: (a) observation of manipulative actions; (b) observation of sequences of random finger movements. In the execution conditions, participants had to perform the same actions or movements as in (a) and (b), respectively. The results of conjunction analysis showed significant shared activations during both observation and execution of manipulation in several subcortical structures, including: (1) cerebellar lobules V, VI, crus I, VIIIa and VIIIb (bilaterally); (2) globus pallidus, bilaterally, and left subthalamic nucleus; (3) red nucleus (bilaterally) and left thalamus. These findings support the hypothesis that the action observation/execution network also involves subcortical structures, such as cerebellum and basal ganglia, forming an integrated network. This suggests possible mechanisms, involving these subcortical structures, underlying learning of new motor skills, through action observation and imitation.
Ultra-compact high efficiency and low crosstalk optical interconnection structures based on inverse designed nanophotonic elements
Authors: Li Zikang , Li Guofeng , Huang Jie , Zhang Zhenrong , Yang Junbo , Yang Changming , Qian Yang , Xu Wenjie , Huang Huimin 
Published: July 2020

AbstractIn this paper, we combine inverse design concept and direct binary search algorithm to demonstrate three ultra-compact high efficiency and low crosstalk on-chip integrated optical interconnection basic devices in the entire wavelength range of 1,400–1600 nm based on silicon-on-insulator platform. A 90-degree waveguide bend with a footprint of only 2.4 × 2.4 μm2 is designed, whose transmission efficiency up to 0.18 dB. A waveguide crossing with a footprint of only 2.4 × 2.4 μm2 is designed, which can provide insertion loss of less than 0.5 dB and crosstalk (CL) of lower than − 19 dB. A same direction waveguide crossing with footprint of only 2.4 × 3.6 μm2 is designed, which can provide the insertion loss of less than 0.56 dB and the crosstalk of lower than − 21 dB. Then, we use them to form several ultra-compact optical interconnect basic structures and performed the simulation calculation. They overall achieve high performance. This will significantly improve the integration density.
KRAS(G12C)–AMG 510 interaction dynamics revealed by all-atom molecular dynamics simulations
Authors: Pantsar Tatu 
Published: July 2020

AbstractThe first KRAS(G12C) targeting inhibitor in clinical development, AMG 510, has shown promising antitumor activity in clinical trials. On the molecular level, however, the interaction dynamics of this covalently bound drug–protein complex has been undetermined. Here, we disclose the interaction dynamics of the KRAS(G12C)–AMG 510 complex by long timescale all-atom molecular dynamics (MD) simulations (total of 75 μs). Moreover, we investigated the influence of the recently reported post-translational modification (PTM) of KRAS’ N-terminus, removal of initiator methionine (iMet1) with acetylation of Thr2, to this complex. Our results demonstrate that AMG 510 does not entrap KRAS into a single conformation, as one would expect based on the crystal structure, but rather into an ensemble of conformations. AMG 510 binding is extremely stable regardless of highly dynamic interface of KRAS’ switches. Overall, KRAS(G12C)–AMG 510 complex partially mimic the native dynamics of GDP bound KRAS; however, AMG 510 stabilizes the α3-helix region. N-terminally modified KRAS displays similar interaction dynamics with AMG 510 as when Met1 is present, but this PTM appears to stabilize β2–β3-loop. These results provide novel conformational insights on the molecular level to KRAS(G12C)–AMG 510 interactions and dynamics, providing new perspectives to RAS related drug discovery.
The prognostic role of preoperative serum albumin/globulin ratio in patients with non-metastatic renal cell carcinoma undergoing partial or radical nephrectomy
Authors: Chung Jae-Wook , Park Dong Jin , Chun So Young , Choi Seock Hwan , Lee Jun Nyung , Kim Bum Soo , Kim Hyun Tae , Kim Tae-Hwan , Yoo Eun Sang , Byun Seok-Soo , Hwang Eu Chang , Kang Seok Ho , Hong Sung-Hoo , Chung Jinsoo , Kwak Cheol , Kim Yong- June , Ha Yun-Sok , Kwon Tae Gyun 
Published: July 2020

AbstractThis multi-institutional study sought to clarify the association between the preoperative serum albumin/globulin ratio (AGR) and the prognosis of renal cell carcinoma (RCC) in a large cohort. This study encompassed eight institutions and 2,970 non-metastatic RCC patients who underwent a radical or partial nephrectomy from the Korean RCC (KORCC) database. A low AGR (1,143 patients; 38.5%) was defined as a preoperative AGR of less than 1.47 and a high AGR (1,827 patients; 61.5%) was defined as that 1.47 or greater. In the low AGR group, older age, female gender, the incidence of symptom presentation when diagnosed, diabetes, and hypertension was higher than in the high AGR group. Patients with low AGRs showed more progressive tumor stages with higher Fuhrman nuclear grades (all P-values < 0.05). Patients in the low AGR group had a significantly lower overall survival rate (OS) and recurrence-free survival rate (RFS) in the Kaplan–Meier curves (all P-values < 0.05). AGR was an independent prognostic factor for predicting the OS and RFS in the multivariate analysis (all P-values < 0.05). The preoperative AGR is approachable and economical to use clinically for estimating the prognosis of RCC patients treated with surgery.
Intracellular interplay between cholecystokinin and leptin signalling for satiety control in rats
Authors: Koizumi Hayato , Mohammad Shahid , Ozaki Tomoya , Muto Kiyokazu , Matsuba Nanami , Kim Juhyon , Pan Weihong , Morioka Eri , Mochizuki Takatoshi , Ikeda Masayuki 
Published: July 2020

AbstractCholecystokinin (CCK) and leptin are satiety-controlling peptides, yet their interactive roles remain unclear. Here, we addressed this issue using in vitro and in vivo models. In rat C6 glioma cells, leptin pre-treatment enhanced Ca2+ mobilization by a CCK agonist (CCK-8s). This leptin action was reduced by Janus kinase inhibitor (AG490) or PI3-kinase inhibitor (LY294002). Meanwhile, leptin stimulation alone failed to mobilize Ca2+ even in cells overexpressing leptin receptors (C6-ObRb). Leptin increased nuclear immunoreactivity against phosphorylated STAT3 (pSTAT3) whereas CCK-8s reduced leptin-induced nuclear pSTAT3 accumulation in these cells. In the rat ventromedial hypothalamus (VMH), leptin-induced action potential firing was enhanced, whereas nuclear pSTAT3 was reduced by co-stimulation with CCK-8s. To further analyse in vivo signalling interplay, a CCK-1 antagonist (lorglumide) was intraperitoneally injected in rats following 1-h restricted feeding. Food access was increased 3-h after lorglumide injection. At this timepoint, nuclear pSTAT3 was increased whereas c-Fos was decreased in the VMH. Taken together, these results suggest that leptin and CCK receptors may both contribute to short-term satiety, and leptin could positively modulate CCK signalling. Notably, nuclear pSTAT3 levels in this experimental paradigm were negatively correlated with satiety levels, contrary to the generally described transcriptional regulation for long-term satiety via leptin receptors.
Pinocembrin alleviates ulcerative colitis in mice via regulating gut microbiota, suppressing TLR4/MD2/NF-κB pathway and promoting intestinal barrier
Authors: Yue Bei , Ren Junyu , Yu Zhilun , Luo Xiaoping , Ren Yijing , Zhang Jing , Mani Sridhar , Wang Zhengtao , Dou Wei 
Published: July 2020

Abstract
Pinocembrin, a plant-derived flavonoid, has a variety of pharmacological activities, including anti-infection, anti-cancer, anti-inflammation, cardiovascular protection, etc. However, the mechanism of pinocembrin on the anti-colitis efficacy remains elusive and needs further investigation. Here, we reported that pinocembrin eased the severity of dextran sulfate sodium (DSS)-induced colitis in mice by suppressing the abnormal activation of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signal pathway in vivo. In addition, the gut microbiota was disordered in DSS colitis mice, which was associated with a significant decrease in microbiota diversity and a great shift in bacteria profiles; however, pinocembrin treatment improved the imbalance of gut microbiota and made it similar to that in normal mice. On the other hand, in vitro, pinocembrin down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated macrophages. At the upstream level, pinocembrin competitively inhibited the binding of LPS to myeloid differentiation protein 2 (MD2), thereby blocking the formation of receptor multimer TLR4/MD2·LPS. Furthermore, pinocembrin dose-dependently promoted the expression of tight junction proteins (ZO-1, Claudin-1, Occludin and JAM-A) in Caco-2 cells. In conclusion, our work presented evidence that pinocembrin attenuated DSS-induced colitis in mouse, at least in part, via regulating intestinal microbiota, inhibiting the over-activation of TLR4/MD2/NF-κB signaling pathway, and improving the barriers of intestine.
Stripped-envelope core-collapse supernova 56Ni masses
Authors: Meza N. , Anderson J. P. 
Published: July 2020

Context. The mass of synthesised radioactive material is an important power source for all supernova (SN) types. In addition, the difference of 56Ni yields statistics are relevant to constrain progenitor paths and explosion mechanisms.
Aims. Here, we re-estimate the nucleosynthetic yields of 56Ni for a well-observed and well-defined sample of stripped-envelope SNe (SE-SNe) in a uniform manner. This allows us to investigate whether the observed hydrogen-rich–stripped-envelope (SN II–SE SN) 56Ni separation is due to real differences between these SN types or because of systematic errors in the estimation methods.
Methods. We compiled a sample of well-observed SE-SNe and measured 56Ni masses through three different methods proposed in the literature: first, the classic “Arnett rule”; second the more recent prescription of Khatami & Kasen (2019, ApJ, 878, 56) and third using the tail luminostiy to provide lower limit 56Ni masses. These SE-SN distributions were then compared to those compiled in this article.
Results. Arnett’s rule, as previously shown, gives 56Ni masses for SE-SNe that are considerably higher than SNe II. While for the distributions calculated using both the Khatami & Kasen (2019, ApJ, 878, 56) prescription and Tail 56Ni masses are offset to lower values than “Arnett values”, their 56Ni distributions are still statistically higher than that of SNe II. Our results are strongly driven by a lack of SE-SN with low 56Ni masses, that are, in addition, strictly lower limits. The lowest SE-SN 56Ni mass in our sample is of 0.015 M⊙, below which are more than 25% of SNe II.
Conclusions. We conclude that there exist real, intrinsic differences in the mass of synthesised radioactive material between SNe II and SE-SNe (types IIb, Ib, and Ic). Any proposed current or future CC SN progenitor scenario and explosion mechanism must be able to explain why and how such differences arise or outline a bias in current SN samples yet to be fully explored.
The orbit of Triton with new precise observations and the INPOP19a ephemeris
Authors: Tang K. , Song Y. Z. , Shen K. X. , Qiao R. C. , Tang Z. H. , Yu Y. , Zhang H. Y. , Yan D. 
Published: July 2020

Aims. The Gaia catalogue brings new opportunities and challenges to high-precision astronomy and astrometry. The precision of data reduction is therefore improved by a large number of reference stars with high-precision positions and proper motions. Numerous precise positions for Triton are obtained from the latest observations using the Gaia catalogue. Furthermore, the new INPOP19a planetary ephemeris, which also fits the observations from the Gaia Data Release 2, has recently become available. In this paper, a new orbit of Triton is calculated using the latest precise charge-coupled device (CCD) observations and the INPOP19a ephemeris.
Methods. Triton’s orbital solution is calculated using a numerical integrator, while the orientation of Neptune’s pole in particular is obtained by integrating the simplified Euler’s equations of motion. We determine the orbit of Triton over 170 yr based on 11 040 Earth-based observations made between 1847 and 2016 and on Voyager 2 data. The positions of the Sun and planets are provided by the INPOP19a ephemeris. We compare our results to those from other previous works to check the influences on Triton’s orbit from different planetary ephemerides.
Results. A new orbit of Triton is provided here. The root-mean-square of the residuals for the Earth-based CCD absolute observations are 0.102″ in right ascension and 0.142″ in declination. Although most different planetary ephemerides have large differences in Neptune’s position, the orbits of Triton using different planetary ephemerides are still close, under similar dynamical models. The Voyager 2 data add a constraint on Triton’s orbit here.
GALACTICNUCLEUS: A high angular-resolution JHKs imaging survey of the Galactic centre
Authors: Nogueras-Lara F. , Schödel R. , Neumayer N. , Gallego-Cano E. , Shahzamanian B. , Gallego-Calvente A. T. , Najarro F. 
Published: July 2020

Context. The characterisation of the extinction curve in the near-infrared (NIR) is fundamental to analysing the structure and stellar population of the Galactic centre (GC), whose analysis is hampered by the extreme interstellar extinction (AV ~ 30 mag) that varies on arc-second scales. Recent studies indicate that the behaviour of the extinction curve might be more complex than previously assumed, pointing towards a variation of the extinction curve as a function of wavelength.
Aims. We aim to analyse the variations of the extinction index, α, with wavelength, line-of-sight, and absolute extinction, extending previous analyses to a larger area of the innermost regions of the Galaxy.
Methods. We analysed the whole GALACTICNUCLEUS survey, a high-angular resolution (~0.2″) JHKs NIR survey specially designed to observe the GC in unprecedented detail. It covers a region of ~6000 pc2, comprising fields in the nuclear stellar disc, the inner bulge, and the transition region between them. We applied two independent methods based on red clump (RC) stars to constrain the extinction curve and analysed its variation superseding previous studies.
Results. We used more than 165 000 RC stars and increased the size of the regions analysed significantly to confirm that the extinction curve varies with the wavelength. We estimated a difference Δα = 0.21 ± 0.07 between the obtained extinction indices, αJH = 2.44 ± 0.05 and αHKs = 2.23 ± 0.05. We also concluded that there is no significant variation of the extinction curve with wavelength, with the line-of-sight or the absolute extinction. Finally, we computed the ratios between extinctions, AJ∕AH = 1.87 ± 0.03 and AH/AKs = 1.84 ± 0.03, consistent with all the regions of the GALACTICNUCLEUS catalogue.