bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADrosophilaRNAi screen reveals conserved glioblastoma-related adhesion genes that regulate collective cell migration
Authors: Kotian Nirupama , Troike Katie M. , Curran Kristen N. , Lathia Justin D. , McDonald Jocelyn A. 
Published: August 2021

ABSTRACTMigrating cell collectives are key to embryonic development but also contribute to invasion and metastasis of a variety of cancers. Cell collectives can invade deep into tissues, leading to tumor progression and resistance to therapies. Collective cell invasion is also observed in the lethal brain tumor glioblastoma, which infiltrates the surrounding brain parenchyma leading to tumor growth and poor patient outcomes.Drosophilaborder cells, which migrate as a small cell cluster in the developing ovary, are a well-studied and genetically accessible model used to identify general mechanisms that control collective cell migration within native tissue environments. Most cell collectives remain cohesive through a variety of cell-cell adhesion proteins during their migration through tissues and organs. In this study, we first identified cell adhesion, cell junction, and associated regulatory genes that are expressed in human brain tumors. We performed RNAi knockdown of theDrosophilaorthologs in border cells to evaluate if migration and/or cohesion of the cluster was impaired. From this screen, we identified eight adhesion genes that disrupted border cell collective migration upon RNAi knockdown. Bioinformatics analyses further demonstrated that subsets of the orthologous genes were elevated in the margin and invasive edge of human glioblastoma patient tumors. These data together show that conserved cell adhesion and adhesion regulatory proteins with potential roles in tumor invasion also modulate collective cell migration. This dual screening approach for adhesion genes linked to glioblastoma and border cell migration thus may reveal conserved mechanisms that drive collective tumor cell invasion.
Pseudomonas aeruginosa C-terminal processing protease CtpA assembles into a hexameric structure that requires activation by a spiral-shaped lipoprotein binding partner
Authors: Hsu Hao-Chi , Wang Michelle , Kovach Amanda , Darwin Andrew J. , Li Huilin 
Published: August 2021

ABSTRACTPseudomonas aeruginosa CtpA is a carboxyl terminal-processing protease that partners with the outer membrane lipoprotein LbcA to degrade at least five cell wall-associated proteins, four of which are cell wall hydrolases. This activity plays an important role in supporting P. aeruginosa virulence in a mouse model of acute pneumonia. However, almost nothing is known about the molecular mechanisms underlying CtpA and LbcA function. Here, we used structural analysis to show that CtpA alone assembles into an inactive hexamer comprising a trimer of dimers, which limits its substrate access and prevents nonspecific degradation. The adaptor protein LbcA is a right-handed open spiral with 11 tetratricopeptide repeats, which might wrap around a substrate to deliver it to CtpA for degradation. By structure-guided mutagenesis and functional assays, we also showed that the interfaces of the CtpA trimer-of-dimers, and an N-terminal helix of LbcA, are important for LbcA-mediated substrate degradation by CtpA both in vitro and in vivo. This work improves our understanding of the molecular mechanism of a CTP within the C-terminal processing peptidase-3 group.IMPORTANCECarboxyl-terminal processing proteases (CTPs) are found in all three domains of life. In bacteria, some CTPs have been associated with virulence, raising the possibility that they could be theraputic targets. However, relatively little is known about their molecular mechanisms of action. In Pseudomonas aeruginosa, CtpA supports virulence by working in complex with the outer membrane lipoprotein LbcA to degrade cell wall hydrolases. Here, we report structure-function analyses of CtpA and LbcA, which reveals that CtpA assembles into an inactive hexamer comprising a trimer of dimers. LbcA is monomeric, with an N-terminal region important for binding to and activating CtpA, followed by a spiral structure composed of 11 tetratricopetide repeats, which could wrap around a substrate for delivery to CtpA. This work provides the first structure of a CTP-3 group member, revealing a unique mutimeric arrangement and insight into how this important proteolytic system functions.
Comparative analysis of machine learning and evolutionary optimization algorithms for precision tissue culture ofCannabis sativa: Prediction and validation ofin vitroshoot growth and development based on the optimization of light and carbohydrate sources
Authors: Pepe Marco , Hesami Mohsen , Small Finlay , Jones Andrew Maxwell Phineas 
Published: August 2021

AbstractMicropropagation techniques offer opportunity to proliferate, maintain, and study dynamic plant responses in highly controlled environments without confounding external influences, forming the basis for many biotechnological applications. With medicinal and recreational interests forCannabis sativaL. growing, research related to the optimization ofin vitropractices is needed to improve current methods while boosting our understanding of the underlying physiological processes. Unfortunately, due to the exorbitantly large array of factors influencing tissue culture, existing approaches to optimizein vitromethods are tedious and time-consuming. Therefore, there is great potential to use new computational methodologies for analysing data to develop improved protocols more efficiently. Here, we first tested the effects of light qualities using assorted combinations of Red, Blue, Far Red, and White spanning 0-100 μmol/m2/s in combination with sucrose concentrations ranging from 1-6 % (w/v), totaling 66 treatments, onin vitroshoot growth, root development, number of nodes, shoot emergence, and canopy surface area. Collected data were then assessed using multilayer perceptron (MLP), generalized regression neural network (GRNN), and adaptive neuro-fuzzy inference system (ANFIS) to model and predictin vitro Cannabisgrowth and development. Based on the results, GRNN had better performance than MLP or ANFIS and was consequently selected to link different optimization algorithms (genetic algorithm, biogeography-based optimization, interior search algorithm, and symbiotic organisms search) for prediction of optimal light levels (quality/intensity) and sucrose concentration for various applications. Predictions ofin vitroconditions to refine growth responses were subsequently tested in a validation experiment and data showed no significant differences between predicted optimized values and observed data. Thus, this study demonstrates the potential of machine learning and optimization algorithms to predict the most favourable light combinations and sucrose levels to elicit specific developmental responses. Based on these, recommendations of light and carbohydrate levels to promote specific developmental outcomes forin vitro Cannabisare suggested. Ultimately, this work showcases the importance of light quality and carbohydrate supply in directing plant development as well as the power of machine learning approaches to investigate complex interactions in plant tissue culture.
In vivo study on the healing of bone defect treated with non-thermal atmospheric pressure gas discharge plasma
Authors: Shimatani Akiyoshi , Toyoda Hiromitsu , Orita Kumi , Hirakawa Yoshihiro , Aoki Kodai , Oh Jun-Seok , Shirafuji Tatsuru , Nakamura Hiroaki 
Published: August 2021

AbstractMedical treatment using non-thermal atmospheric pressure gas discharge plasma is rapidly gaining recognition. Gas discharge plasma is thought to generate highly reactive species in an ambient atmosphere, which could be exposed to biological targets (e.g., cells and tissues). If plasma-generated reactive species could stimulate bone regeneration, gas discharge plasma could provide a new treatment opportunity in regenerative medicine. We investigated the impact of plasma on bone regeneration using a large bone defect in model rabbits and simple atmospheric pressure plasma (helium microplasma jet). We tracked the recovery progress of the large bone defects by X-ray imaging over eight weeks. The X-ray results showed a clear difference in the filling of the large bone defect among groups with different plasma treatment times, whereas filling was not substantial in the untreated control group. According to the results of micro-computed tomography analysis at eight weeks, the most successful bone regeneration was achieved using a plasma treatment time of 10 min, wherein the new bone volume was 1.51 times larger than that in the control group. Overall, these results suggest that non-thermal atmospheric pressure gas discharge plasma is promising for fracture treatment.
Investigating the active substance and mechanism of Jing-Fu-Kang granules via mass spectrometry technology and network pharmacology method
Authors: Feng Xin , Bi Yuelin , Gao Xuhua , Wu Hao , Li Tianyi , Liu Runhua , Sun Yu , Wang Jiaqi , Fang Linlin , Zhang Chenning , Sun Yikun 
Published: August 2021

AbstractJing-Fu-Kang granules (JFKG) is a famous Chinese patent medicine for the treatment of cervical spondylosis around the China, whereas the active substance and mechanism are not completely investigated clearly. In the current study, a rapid separation and identification method using UPLC-QE-Orbitrap-MS was established, 97 chemical constituents from JFKG were identified, and 16 prototype components from plasma samples after administration of JFKG were observed within 16 min. The structures of typical compounds were preliminarily speculated by comparing the retention time and fragmentation pattern. Furthermore, multiple databases were used to integrate the compound targets of JFKG, and the disease targets related to cervical spondylosis. After the intersection of the two sets of targets, a protein-protein interaction (PPI) network and a TCM-component-target-pathway-disease network were established, then using the DAVID database to perform gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the common targets to find related pathways. Finally, a total of 531 common targets and 136 pathways were found to participate in the mechanism. Our findings will help to further confirm the mechanism of JFKG for relieving cervical spondylosis, which will improve the scientific rationality of JFKG in clinical use, and can also assist in guiding doctors.
Characterizing the performance of human leg external force control
Authors: Kudzia Pawel , Robinovich Stephen N. , Maxwell Donelan J. 
Published: August 2021

AbstractOur legs act as our primary contact with the surrounding environment, generating external forces that enable agile motion. To be agile, the nervous system has to control both the magnitude of the force that the feet apply to the ground and the point of application of this force. The purpose of this study was to characterize the performance of the healthy human neuromechanical system in controlling the force-magnitude and position of an externally applied force. To accomplish this, we built an apparatus that immobilized participants but allowed them to exert variable but controlled external forces with a single leg onto a ground embedded force plate. We provided real-time visual feedback of either the leg force-magnitude or position that participants were exerting against the force platform and instructed participants to best match their real-time signal to prescribed target step functions. We tested target step functions of a range of sizes and quantified the responsiveness and accuracy of the control. For the control of force-magnitude and for intermediate step sizes of 0.45 bodyweights, we found a bandwidth of 1.8±0.5 Hz, a steady-state error of 2.6±0.9%, and a steady-state variability of 2.7±0.9%. We found similar control performance in terms of responsiveness and accuracy across step sizes and between force-magnitude and position control. Increases in responsiveness correlated with reductions in other measures of control performance, such as a greater magnitude of overshooting. We modelled the observed control performance and found that a second-order model was a good predictor of external leg force control. We discuss how benchmarking force control performance in young healthy humans aids in understanding differences in agility between humans, between humans and other animals, and between humans and engineered systems.
Matthew effect: common species become more common and rare ones become more rare in response to artificial light at night
Authors: Liu Yanjie , Speißer Benedikt , Knop Eva , van Kleunen Mark 
Published: August 2021

AbstractArtificial light at night (ALAN) has been and still is rapidly spreading, and has become an important component of global change. Although numerous studies have tested its potential biological and ecological impacts on animals, fewer have tested its impacts on plants, and very few studies have tested whether it affects alien and native plants differently. Furthermore, common plant species, and particularly common alien species, are often found to benefit more from additional resources than rare native and rare alien species. Whether this is also the case with regard to increasing light due to ALAN is still unknown.Here, we tested how ALAN affects the performance of common and rare alien and native plants directly and indirectly via flying insects. We grew five common alien, six rare alien, five common native and four rare native plant species under four combinations of two ALAN (no ALANvsALAN) and two insect-exclusion (no exclusionvsexclusion) treatments, and compared their biomass production.We found that common plant species, irrespective of whether they are alien or native, produced significantly more biomass than rare species, particularly under ALAN. Furthermore, alien species tended to show a slightly stronger positive response to ALAN than native species (marginally significant origin × ALAN interaction,p= 0.079).Our study shows that common plant species benefited more from ALAN than rare ones. This might lead to shifts in plant diversity and vegetation composition, further propelling global biodiversity decline, when ALAN becomes more widespread. In addition, the slightly more positive response of alien species indicates that ALAN might increase the risk of alien plant invasions.
Associations between different tau-PET patterns and longitudinal atrophy in the Alzheimer’s disease continuum
Authors: Mohanty Rosaleena , Ferreira Daniel , Nordberg Agneta , Westman Eric ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2021

ABSTRACTINTRODUCTIONDifferent subtypes/patterns have been defined using tau-PET and structural-MRI in Alzheimer’s disease (AD), but the relationship between tau pathology and atrophy remains unclear. Our goals were twofold: (a) investigate the association between baseline tau-PET patterns and longitudinal atrophy in the AD continuum; (b) characterizeheterogeneityas a continuous phenomenon over the conventional notion using discrete subgroups.METHODSIn 366 individuals (amyloid-beta-positive: cognitively normal, prodromal AD, AD dementia; amyloid-beta-negative healthy), we examined the association between tau-PET patterns (operationalized as a continuous phenomenon and a discrete phenomenon) and longitudinal sMRI.RESULTSWe observed a differential association between tau-PET patterns and longitudinal atrophy. Heterogeneity, measured continuously, may offer an alternative characterization, sharing correspondence with the conventional subgrouping.DISCUSSIONSite and the rate of atrophy are modulated differentially by tau-PET patterns in the AD continuum. We postulate thatheterogeneitybe treated as a continuous phenomenon for greater sensitivity over the current/conventional discrete subgrouping.
Neuronal mimicry generates an ecosystem critical for brain metastatic growth of SCLC
Authors: Qu Fangfei , Cao Siqi , Michno Wojciech , Madubata Chioma J. , Puno Alyssa , Drainas Alexandros P. , Lee Myung Chang , Yang Dian , Toland Angus , Kong Christina , Das Millie , Winslow Monte M. , Paşca Anca M. , Sage Julien 
Published: August 2021

ABSTRACTBrain metastasis is a major cause of morbidity and mortality in cancer patients. Here we investigated mechanisms allowing small-cell lung cancer (SCLC) cells to grow in the brain. We show that SCLC cells undergo a cell state transition towards neuronal differentiation during tumor progression and metastasis, and that this neuronal mimicry is critical for SCLC growth in the brain. Mechanistically, SCLC cells re-activate astrocytes, which in turn promote SCLC growth by secreting neuronal pro-survival factors such as SERPINE1. We further identify Reelin, a molecule important in brain development, as a factor secreted by SCLC cells to recruit astrocytes to brain metastases in mice. This recruitment of astrocytes by SCLC was recapitulated in assembloids between SCLC aggregates and human cortical spheroids. Thus, SCLC brain metastases grow by co-opting mechanisms involved in reciprocal neuron-astrocyte interactions during development. Targeting such developmental programs activated in this cancer ecosystem may help treat brain metastases.
A two-stage approach for the spatio-temporal analysis of high-throughput phenotyping data
Authors: Pérez-Valencia Diana M. , Rodríguez-Álvarez María Xosé , Boer Martin P. , Kronenberg Lukas , Hund Andreas , Cabrera-Bosquet Llorenç , Millet Emilie J. , van Eeuwijk Fred A. 
Published: August 2021

ABSTRACTHigh throughput phenotyping (HTP) platforms and devices are increasingly used for the characterization of growth and developmental processes for large sets of plant genotypes. Such HTP data require challenging statistical analyses in which longitudinal genetic signals need to be estimated against a background of spatio-temporal noise processes. We propose a two-stage approach for the analysis of such longitudinal HTP data. In a first stage, we correct for design features and spatial trends per time point. In a second stage, we focus on the longitudinal modelling of the spatially corrected data, thereby taking advantage of shared longitudinal features between genotypes and plants within genotypes. We propose a flexible hierarchical three-level P-spline growth curve model, with plants/plots nested in genotypes, and genotypes nested in populations. For selection of genotypes in a plant breeding context, we show how to extract new phenotypes, like growth rates, from the estimated genotypic growth curves and their first-order derivatives. We illustrate our approach on HTP data from the PhenoArch greenhouse platform at INRAE Montpellier and the outdoor Field Phenotyping platform at ETH Zürich.
Implementing solid-phase-enhanced sample preparation for Co-Immunoprecipitation with Mass Spectrometry forC. elegans
Authors: Baytek Gülkiz , Popp Oliver , Mertins Philipp , Tursun Baris 
Published: August 2021

AbstractStudying protein-protein interactionsin vivocan reveal key molecular mechanisms of biological processes. Co-Immunoprecipitation followed by Mass Spectrometry (CoIP-MS) allows detection of protein-protein interactions in high-throughput. The nematodeCaenorhabditis elegans (C. elegans)is a powerful genetic model organism forin vivostudies. Yet, its rigid cuticle and complex tissues require optimization for protein biochemistry applications to ensure robustness and reproducibility of experimental outcomes. Therefore, we optimized CoIP-MS application toC. elegansprotein lysates by combining a native CoIP procedure with an efficient sample preparation method called single-pot, solid-phase-enhanced, sample preparation method (SP3). Our results based on the subunits of the conserved chromatin remodeler FACT demonstrate that our SP3-integrated CoIP-MS procedure forC. eleganssamples is highly accurate and robust. Moreover, in a previous study (Baytek et al. 2021), we extended our technique to studying the chromodomain factor MRG-1 (MRG15 in human), which resulted in unprecedented findings.Method SummaryCombination of cryo-fracture with single-pot, solid-phase-enhanced, sample preparation (SP3) to perform Co-Immuno-Precipitation followed by Mass Spectrometry (CoIP-MS) provides robust assessments of protein-protein interaction usingC. eleganswhole animals.
Transient lightning response to grounding grids buried in horizontal multilayered earth model considering time domain quasi-static complex image method and soil ionization effect
Authors: Li Zhong-Xin , Li Peng , Wang Ke-Chao 
Published: August 2021

PurposeThe purpose of this paper is to propose a fast, accurate and efficient algorithm for assessment of transient behavior of grounding grids buried in horizontal multilayered earth model considering soil ionization effect.Design/methodology/approachThe purpose of this paper is to develop a numerical simulation method to calculate the lightning impulse response of the grounding grid buried in a horizontal multilayered earth model. The mathematical model about the hybrid method based on PI basic function belonging to time domain is proposed in the paper; the mode can precisely calculate the lightning current distribution and lightning impulse response to grounding grids buried in horizontal multilayered soil model considering soil ionization effect. To increase computing efficiency, quasi-static complex image method (QSCIM) and its time-domain Green’s function closed form are introduced in the model.FindingsThe hybrid model is rather stable, with the respect to the number of elements used and with excellent convergence rate. In addition, because this mathematical model belongs to the time domain algorithm, it is very powerful for the simulation of soil ionization caused by high amplitude lightning current.Research limitations/implicationsTo increase computing efficiency, QSCIM and its time domain Green's function closed form are introduced in the model.Practical implicationsThe mathematical model about the hybrid method based on PI basic function can precisely calculate the lightning current distribution and lightning impulse response to grounding grids buried in horizontal multilayered soil model considering the soil ionization effect.Social implicationsConsidering the soil ionization effect, the simulation calculation of lightning impulse response of substation grounding grid buried in the actual horizontal multilayered earth can effectively support the scientific and efficient design of lightning protection performance of substation grounding grid.Originality/valueThe hybrid model in time domain is originally developed by the authors and used to precisely calculate the lightning current distribution and lightning impulse response to grounding grids buried in horizontal multilayered soil model considering soil ionization effect. It is simple and very efficient and can easily be extended to arbitrary grounding configurations.
Budget deficits, money growth and inflation: empirical evidence from Vietnam
Authors: Khieu Hoang Van 
Published: August 2021

PurposeThis paper aims to uncover the nexus between budget deficits, money growth and inflation in Vietnam in the period 1995–2012.Design/methodology/approachThe paper uses a structural vector auto-regressive model of five endogenous variables including inflation, real GDP growth, budget deficit growth, money growth and the interest rate.FindingsIt is found that inflation rose in response to positive shocks to money growth and that budget deficits had no significant impact on money growth and therefore inflation. This empirical evidence supports the hypothesis that fiscal and monetary policies were relatively independent. Money growth significantly decreased in response to a positive shock to inflation; interest rates had no significant effect on inflation but considerably increased in response to positive inflation shocks. This implies that the monetary base was more effective than interest rates in fighting inflation.Originality/valueThis paper sheds light into understanding the link between budget deficits, money growth and inflation in Vietnam during the high-inflation period 1995–2012. The finding supports the hypothesis that fiscal and monetary policies were relatively independent over the period.