bluuebunny/crossref_metadata_2025_split huggingface dataset:
The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress
Authors: Sthijns Mireille M.J.P.E. , Rademakers Timo , Oosterveer Jolien , Geuens Thomas , van Blitterswijk Clemens A. , LaPointe Vanessa L.S. 
Published: September 2021

AbstractThe pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their composition can be optimized to diminish oxidative stress. We investigated how the ratio of the two main islet cell types (alpha and beta cells) and their culture in three-dimensional aggregates could protect against oxidative stress. Monolayer and aggregate cultures were established by seeding the alphaTC1 (alpha) and INS1E (beta) cell lines in varying ratios, and hydrogen peroxide was applied to induce oxidative stress. Viability, oxidative stress, and the level of the antioxidant glutathione were measured. Both aggregation and an increasing prevalence of INS1E cells in the co-cultures conferred greater resistance to cell death induced by oxidative stress. Increasing the prevalence of INS1E cells also decreased the number of alphaTC1 cells experiencing oxidative stress in the monolayer culture. In 3D aggregates, culturing the alphaTC1 and INS1E cells in a ratio of 50:50 prevented oxidative stress in both cell types. Together, the results of this study lead to new insight into how modulating the composition and dimensionality of a co-culture can influence the oxidative stress levels experienced by the cells.
High Temporal Resolution Measurements of Movement Reveal Novel Early-Life Physiological Decline in C. elegans
Authors: Sinha Drew B. , Pincus Zachary S. 
Published: September 2021

AbstractAge-related physiological changes are most notable and best-studied late in life, while the nature of aging in early- or middle-aged individuals has not been explored as thoroughly. In C. elegans, studies of movement vs. age generally delineate three distinct phases: sustained, youthful movement; a discrete onset of rapidly progressing impairment; and gross immobility. We investigated whether this first period of early-life adult movement is simply a sustained “healthy” level of high function followed by a discrete “movement catastrophe” — or whether there are early-life changes in movement that precede future physiological declines. To determine how movement varies during early adult life, we followed isolated individuals throughout life with a previously unachieved combination of duration and temporal resolution. By tracking individuals across the first six days of adulthood, we observed declines in movement starting as early as the first two days of adult life, as well as high interindividual variability in total daily movement. These findings suggest that movement is a highly dynamic behavior early in life, and that factors driving movement decline may begin acting as early as the first day of adulthood. Using simulation studies based on acquired data, we suggest that too infrequent sampling in common movement assays limits observation of early-adult changes in motility, and we propose feasible alternate strategies and a framework for designing assays with increased sensitivity for early movement declines.
External drivers of BOLD signal’s non-stationarity
Authors: Ashourvan Arian , Pequito Sérgio , Bertolero Maxwell , Kim Jason Z. , Bassett Danielle S. , Litt Brian 
Published: September 2021

AbstractA fundamental challenge in neuroscience is to uncover the principles governing how the brain interacts with the external environment. However, assumptions about external stimuli fundamentally constrain current computational models. We show in silico that unknown external stimulation can produce error in the estimated linear time-invariant dynamical system. To address these limitations, we propose an approach to retrieve the external (unknown) input parameters and demonstrate that the estimated system parameters during external input quiescence uncover spatiotemporal profiles of external inputs over external stimulation periods more accurately. Finally, we unveil the expected (and unexpected) sensory and task-related extra-cortical input profiles using functional magnetic resonance imaging data acquired from 96 subjects (Human Connectome Project) during the resting-state and task scans. Together, we provide evidence that this embodied brain activity model offers information about the structure and dimensionality of the BOLD signal’s external drivers and shines light on likely external sources contributing to the BOLD signal’s non-stationarity.
Declining RNA integrity in control autopsy brain tissue is robustly and asymmetrically associated with selective neuronal mRNA signal loss
Authors: Johnson Eleanor S. , Stenzel Kendra E. , Lee Sangderk , Blalock Eric M. 
Published: September 2021

AbstractRNA integrity numbers (RINs) are a standardized method for semi-quantification of RNA degradation, and are used in quality control prior to transcriptional profiling analysis. Recent work has demonstrated that RINs are associated with downstream transcriptional profiling, and correction procedures are typically employed in bioinformatic analysis pipelines to attempt to control for RIN’s influence on gene expression. However, relatively little work has been done to determine whether RIN’s influence is random, or is specifically targeted to a subset of mRNAs. We tested the hypothesis that RIN would be associated with a robust transcriptional profile seen across multiple studies.To test this, we downloaded subsets of raw transcriptional data from six published studies. We only included control, non-pathological post-mortem human brain tissue (n = 383 samples) in which independent subjects’ RIN values were also reported. A robust set of mRNAs consistently and significantly correlated with RIN across multiple studies, appearing to be selectively degraded as RIN declines. Many of the affected gene expression pathways are related to neurons (e.g., vesicle, mRNA transport, synapse, and mitochondria), suggesting that neuronal synaptic mRNA may be particularly vulnerable to degradation. Subsequent analysis of the relationship between RIN and vulnerable mRNA expression revealed most of the decay occurred over a relatively narrow RIN range of 7.2-8.6, with RIN values > 8.6 showing a ceiling effect, and those < 7.2 showing a floor effect on gene expression. Our data suggests that the RIN effect is pathway selective and non-linear, which may be an important consideration for current bioinformatic RIN correcting procedures, particularly in datasets in which declining RIN is confounded with a pathology under study (e.g., in Alzheimer’s disease).
Gene Set Analysis for time-to-event outcome with the Generalized Berk–Jones statistic
Authors: Villain Laura , Ferté Thomas , Thiébaut Rodolphe , Hejblum Boris P. 
Published: September 2021

SummaryGene Set analysis allows to evaluate the impact of groups of genes on an outcome of interest, such as the occurrence of a disease. Through the definition of the gene sets, gene set analysis takes into account biological knowledge and makes it easier to interpret the results, while improving the statistical power compared to a gene-wise analysis. In the time-to-event context, few methods exist, but most of them do not take into account the correlation that occurs inside a gene set, which can be strong. As the Generalized Berk-Jones statistics showed great consistency and includes the correlation inside the test statistic, we adapted this method to the time-to-event context by using a Cox model. We compared our approach to other methods based on the Cox model, and showed that the Generalize Berk-Jones statistic offers great adaptability, meaning that it can be used in all kinds of data structures. We applied the different methods to two different contexts: Gliomas and Breast cancer. In terms of statistical power, we did offer similar results to the other Cox model methods, but with greater accuracy. In the breast cancer framework, we showed better statistical power than methods based on Kernel Machine score.
A unique sulfotransferase-involving strigolactone biosynthetic route in Sorghum
Authors: Wu Sheng , Li Yanran 
Published: September 2021

ABSTRACTLOW GERMINATION STIMULANT 1 (LGS1) plays an important role in strigolactones (SLs) biosynthesis and Striga resistance in sorghum but the catalytic function remains unclear. Using the recently developed SL-producing microbial consortia, we examined the activities of sorghum MAX1 analogs and LGS1. Surprisingly, SbMAX1d (accession # XP_002458367) synthesized 18-hydroxy-carlactonoic acid (18-hydroxy-CLA) directly from carlactone (CL) through four-step oxidations, and addition of LGS1 led to the synthesis of both 5-deoxystrigol (5DS) and 4-deoxyorobanchol (4DO). Further biochemical characterization found that LGS1 functions after SbMAX1d by converting 18-hydroxy-CLA to 18-sulphate-CLA to provide an easier leaving group to afford a spontaneous formation of 5DS and 4DO. The unique functions of SbMAX1 and LGS1 imply a previously unknown synthetic route towards strigolactones.Abstract Figure
Transcriptional regulation of HSCs in Aging and MDS reveals DDIT3 as a Potential Driver of Dyserythropoiesis
Authors: Berastegui Nerea , Ainciburu Marina , Romero Juan P. , Alfonso-Pierola Ana , Philippe Céline , Vilas Amaia , Martin Patxi San , Ordoñez Raquel , Alignani Diego , Sarvide Sarai , Castro Laura , Lamo-Espinosa José M. , San-Julian Mikel , Jimenez Tamara , López Félix , Muntion Sandra , Sanchez-Guijo Fermin , Molero Antonieta , Montoro Julia , Tazón Bárbara , Serrano Guillermo , Diaz-Mazkiaran Aintzane , Hernaez Mikel , Huerga Sofía , Copley Findlay , Rio-Machin Ana , Maurano Matthew T. , Díez-Campelo María , Valcarcel David , Rouault-Pierre Kevin , Lara-Astiaso David , Ezponda Teresa , Prosper Felipe 
Published: September 2021

ABSTRACTMyelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis, with increased incidence in elderly individuals. In this work, we analyzed the transcriptome of human HSCs purified from young and elderly healthy donors, as well as MDS patients, identifying transcriptional alterations following eight different patterns of expression. While aging-associated lesions seemed to predispose HSCs to myeloid transformation, disease-specific alterations may trigger MDS development. Among MDS-specific lesions, we detected the upregulation of the transcription factor DDIT3. Overexpression of DDIT3 in human healthy HSCs induced an MDS-like transcriptional state, and a delay in erythropoiesis. Such effect was associated with downregulation of transcription factors required for normal erythropoiesis, and with a failure in the activation of their transcriptional programs. Moreover, DDIT3 knockdown in CD34+ cells from MDS patients with anemia was able to restore erythropoiesis. These results identify DDIT3 as a driver of dyserythropoiesis, and a potential therapeutic target to restore the inefficient erythropoiesis characterizing MDS patients.STATEMENT OF SIGNIFICANCEThis study defines how human aging and MDS development are characterized by transcriptional alterations in HSCs that follow different patterns, some of which may contribute to myeloid transformation. Among them, we demonstrate how MDS-specific upregulation of DDIT3 in HSCs induces dyserythropoiesis, while its knockdown in HSPCs from MDS patients restores proper erythroid differentiation.
α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization
Authors: Ma Dandan , Wang Rongyi , Wang Fulin , Chen Zhiquan , Huang Ning , Xia Yuqing , Teng Junlin , Chen Jianguo 
Published: September 2021

AbstractThe centrosome, composed of a pair of centrioles (mother and daughter centrioles) and pericentriolar material, is mainly responsible for microtubule nucleation and anchorage in animal cells. The subdistal appendage (SDA) is a centriolar structure located at the subdistal region on the mother centriole, and it functions in microtubule anchorage. However, the molecular composition and detailed structure of SDA remain largely unknown. Here, we identified a-taxilin and r-taxilin as new SDA components, which form a complex via their coiled-coil domains and serve as a new subgroup during SDA hierarchical assembly. Their SDA localization is dependent on ODF2, and α-taxilin recruits CEP170 to the SDA. Functional analyses suggest that α-taxilin and γ-taxilin are responsible for centrosomal microtubule anchorage during interphase, as well as for proper spindle orientation during metaphase. Altogether, our results shed light on the molecular components and functional understanding of the SDA hierarchical assembly and microtubule organization.
Copper selects for siderophore-mediated virulence in Pseudomonas aeruginosa
Authors: Lear Luke , Hesse Elze , Buckling Angus , Vos Michiel 
Published: September 2021

AbstractIron is essential for almost all bacterial pathogens and consequently it is actively withheld by their hosts. However, the production of extracellular siderophores enables iron sequestration by pathogens, increasing their virulence. Another function of siderophores is extracellular detoxification of non-ferrous metals. Here, we experimentally link the detoxification and virulence roles of siderophores by testing whether the opportunistic pathogen Pseudomonas aeruginosa displays greater virulence after exposure to copper. To do this, we incubated P. aeruginosa under different environmentally relevant copper regimes for either two or twelve days. Subsequent growth in a copper-free environment removed phenotypic effects, before we quantified pyoverdine production (the primary siderophore produced by P. aeruginosa), and virulence using the Galleria mellonella infection model. Copper selected for increased pyoverdine production, which was positively correlated with virulence. This effect increased with time, such that populations incubated with high copper for twelve days were the most virulent. Replication of the experiment with a non-pyoverdine producing strain of P. aeruginosa demonstrated that pyoverdine production was largely responsible for the change in virulence. Therefore we here show a direct link between metal stress and bacterial virulence, highlighting another dimension of the detrimental effects of metal pollution on human health.
Finite element study on residual internal pressure strength of corroded oil pipes and prediction method for remaining life
Authors: Yuan Yue , Deng Kuanhai , Zhang Jiangjiang , Zeng Wenguang , Kong Xiangwei , Lin Yuanhua 
Published: September 2021

Purpose
This study aims to provide a theoretical basis to evaluate the suitability and integrity of corrosion pipes.

Design/methodology/approach
The three-dimensional models of the P110S oil pipe with local corrosion damage, general corrosion damage, pitting corrosion damage are established based on the API 579 standard using the nonlinear finite element analysis method for parametric research.

Findings
The reliability of the model is verified based on the experimental data from the existing literature. The effects of the oil pipe’s size and the corrosion damage’s type on the residual internal pressure strength are simulated and obtained. What’s more, a basic method for predicting the remaining life of corrosion damaged pipes is proposed.

Originality/value
The authors evaluated the residual strength of various corroded tubing, compared the tubing with different corrosion types and proposed a basic method for predicting the remaining life of the corroded tubing from the corrosion depth.
Dependence of hydrogen embrittlement on annealing time in medium-Mn steels
Authors: Xu Juanping , Li Jinxu , Wang Zheng , Fu Hao , Wu Ming 
Published: September 2021

PurposeThe purpose of this paper is to investigate the effect of the soft annealing time on the microstructure and hydrogen embrittlement (HE) of Fe-0.22C-11.54Mn-2.05Al steels.Design/methodology/approachSteels A and B with different morphologies were prepared by cold rolling after warm rolling, long/short softening annealing and finally annealing at 700 °C for 30 min. Uncharged and charged samples were subjected to tensile, and HE behavior was studied by electron backscattered diffraction, scanning electron microscopy and X-ray diffraction.FindingsThe two samples exhibited similar tensile strengths. The homogeneous equiaxed microstructure of steel B was found to be more conducive to relieve its HE sensitivity. Steel A exhibited bimodal-grained microstructures – blocky and lath. The formation of crack in the blocky grains of steel A resulted in a significant reduction in its plasticity and tensile strength.Originality/valueThe high HE susceptibility of steel A is mainly connected with the inhomogeneity of martensite transformation.
An investigation on cutting of the cold work steel X153CrMoV12 by WEDM
Authors: Ceritbinmez Ferhat 
Published: September 2021

Purpose
Wire electric discharge machining (WEDM) is a non-conventional machining process, which is used for cutting parts of civil and military aircraft, rotorcraft, satellites and spacecraft. The cold work steel X153CrMoV12 is used in molds that are needed to produce plastic and metal parts used in these areas. It is only possible to produce parts with precise dimensions and quality with the use of mold steels with sensitive surfaces. The purpose of this study is to analyze X153CrMoV12 material by cutting it with WEDM method in precise dimensions.

Design/methodology/approach
The effects of varying cutting parameters on the size of the finished product, surface roughness (SR) and surface hardness were determined by making rough in one pass and precision cuts in different passes. Nikon SMZ745T, Mitutoyo micrometer, Mitutoyo SJ-210 and Insize ISHL-P100 were used for macro-analysis, dimensional control, SR and surface hardness, respectively, to determine the cut qualities.

Findings
According to the hardness measurement results obtained from the steel surface before cutting and from the cut surfaces after cutting, there was no significant change in the surface hardness owing to the use of heat-treated steel. Increasing the wire tension as a result of the increase in the number of cutting passes and the decrease in the amount of rough stock left for the final cut increased the cut quality. Cutting precision has increased by preventing vibration of the wire with zero upper and lower water pressure required for slag cleaning.

Originality/value
There are many studies on WEDM in the literature, but there is no similar study emphasizing the importance of the processing parameters such as the number of cutting passes and rough stock amount. In this study, cold work steel with a hardness of 56–60 HRC was machined as rough cut in one pass, rough and fine cut in double pass, double fine cut after one roughing in three passes. As a result of the cuts, 3 µm measurement precision and 0.998 Ra SR were obtained as well as there was no hardness change in the cut surfaces.
A review of experimental techniques to predict aircraft spin and recovery characteristics
Authors: Malik Bilal , Masud Jehanzeb , Akhtar Suhail 
Published: September 2021

Purpose
This paper aims to provide a detailed review of the experimental research on the prediction of aircraft spin and recovery characteristics using dynamically scaled aircraft models.

Design/methodology/approach
The paper organizes experimental techniques to predict aircraft spin and recovery characteristics into three broad categories: dynamic free-flight tests, dynamic force tests and a relatively novel technique called wind tunnel based virtual flight testing.

Findings
After a thorough review, usefulness, limitations and open problems in the presented techniques are highlighted to provide a useful reference to researchers. The area of application of each technique within the research scope of aircraft spin is also presented.

Originality/value
Previous reviews on the prediction of aircraft spin and recovery characteristics were published many years ago and also have confined scope as they address particular spin technologies. This paper attempts to provide a comprehensive review on the subject and fill the information void regarding the state of the art aircraft spin technologies.
Impacts of inflation on gold price and exchange rate in Vietnam: time-varying vs fixed coefficient cointegrations
Authors: Long Pham Dinh , Hien Bui Quang , Ngoc Pham Thi Bich 
Published: September 2021

PurposeThe paper aims to shed light on the effects of inflation on gold price and exchange rate in Vietnam by using time-varying cointegration.Design/methodology/approachUsing cointegration techniques with fixed coefficient and time-varying coefficient, the study exams the impacts of inflation in models and compares the results through coefficient estimates.FindingsA significant inflation impacts are found with the time-varying cointegration but not with the fixed coefficient cointegration models. Moreover, monetary policy affects exchange rate not only directly via its instruments as money supply and interest rate but indirectly via inflation. Also, interest rate is one of the determinants of gold price.Originality/valueTo the best of our knowledge, this paper is the first to use time-varying cointegration to analyze the impact of inflation on the gold price and exchange rate in Vietnam. Gold price and exchange rate fluctuations are always the essential and striking issues, which have been emphasized by economists and policymakers. In macroeconometric researches, cointegration models are often used to analyze the long-term relations between variables. Attentionally, applied models show a limitation when estimating coefficients are fixed. This characteristic might not really match with the data properties and the variation of the economy. Currently, time-varying cointegration models are emerging method to solve the above issue.