bluuebunny/crossref_metadata_2025_split huggingface dataset:
Template-assisted fabrication of moon-shaped channels for protein breakthrough analysis
Authors: Moorthy Raghu K. , D’Souza Serena , Sunthar P. , Noronha Santosh B. 
Published: September 2023

AbstractCylindrical column with packed stationary phase is the workhorse of liquid chromatography systems. These stationary phases are commonly classified on the basis of different form factors namely, beads and monoliths for protein chromatography. Monolithic rods are one of the important geometries derived from polymers through complex polymerization schemes with additional requirements such as cross-linkers and specific reaction conditions. To address these practical difficulties and enable ease of fabrication at laboratory scale, acrylic copolymers are hypothesized to perform as a monolithic stationary phase suitable for protein chromatography. The present work proposes a rapid fabrication technique to obtain monolithic rods that could be reconditioned without any of the above additional steps. It is characterized with monolith diameter that could be controlled using acrylic copolymer concentration. Formation of the copolymeric stationary phase inside microchannel led to annular geometry and in turn, demonstrated fabrication of moon-shaped channels (MSCs) for the first time in literature. An online monitoring system facilitated tracer breakthrough analysis with MSCs to report sharp peak front and an estimate of channel void volume. Breakthrough curves with single protein validated the selection of blue dextran as tracer and indicated retention of proteins due to electrostatic interactions on the functional copolymer surface.
Macrophage subpopulation identity inDrosophilais modulated by apoptotic cell clearance and related signalling pathways
Authors: Brooks Elliot C. , Zeidler Martin P. , Ong Albert C. M. , Evans Iwan R. 
Published: September 2023

AbstractInDrosophilablood, plasmatocytes of the haemocyte lineage represent the functional equivalent of vertebrate macrophages and have become an establishedin vivomodel with which to study macrophage function and behaviour. However, the use of plasmatocytes as a macrophage model has been limited by a historical perspective that plasmatocytes represent a homogenous population of cells, in contrast to the high levels of heterogeneity of vertebrate macrophages. Recently, a number of groups have reported transcriptomic approaches which suggest the existence of plasmatocyte heterogeneity, while we identified enhancer elements that identify subpopulations of plasmatocytes which exhibit potentially pro-inflammatory behaviours, suggesting conservation of plasmatocyte heterogeneity inDrosophila. These plasmatocyte subpopulations exhibit enhanced responses to wounds and decreased rates of efferocytosis when compared to the overall plasmatocyte population. Interestingly, increasing the phagocytic requirement placed upon plasmatocytes is sufficient to decrease the size of these plasmatocyte subpopulations in the embryo. However, the mechanistic basis for this response was unclear. Here, we examine how plasmatocyte subpopulations are modulated by apoptotic cell clearance (efferocytosis) demands and associated signalling pathways. We show that loss of the phosphatidylserine receptor Simu prevents an increased phagocytic burden from modulating specific subpopulation cells, while blocking other apoptotic cell receptors revealed no such rescue. This suggests that Simu-dependent efferocytosis is specifically involved in determining fate of particular subpopulations. Supportive of our original finding, mutations inamo(theDrosophilahomolog ofPKD2), a calcium-permeable channel which operates downstream of Simu, phenocopysimumutants. Furthermore, we show that Amo is involved in the acidification of the apoptotic cell-containing phagosomes, suggesting that this reduction in pH may be associated with macrophage reprogramming. Additionally, our results also identify Ecdysone receptor signalling, a pathway related to control of cell death during developmental transitions, as a controller of plasmatocyte subpopulation identity. Overall, these results identify fundamental pathways involved in the specification of plasmatocyte subpopulations and so further validateDrosophilaplasmatocytes as a heterogeneous population of macrophage-like cells within this important developmental and immune model.
Olfactory learning inDrosophilarequires O-GlcNAcylation of mushroom body ribosomal subunits
Authors: Yu Haibin , Liu Dandan , Zhang Yaowen , Tang Ruijun , Fan Xunan , Mao Song , Lv Lu , Chen Fang , Qin Hongtao , Zhang Zhuohua , van Aalten Daan M.F. , Yang Bing , Yuan Kai 
Published: September 2023

AbstractO-GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an O-GlcNAc binding activity derived fromClostridium perfringensOGA (CpOGA) with TurboID proximity labeling inDrosophila, we developed an O-GlcNAcylation profiling tool that translates O-GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the O-GlcNAc interactome in major brain regions ofDrosophilaand found that components of the translational machinery, including many ribosomal subunits, were abundantly O-GlcNAcylated in the mushroom body, the computational center of theDrosophilabrain. Hypo-O-GlcNAcylation induced by ectopic expression of activeCpOGA in the mushroom body decreased local ribosomal activity, leading to olfactory learning deficits that could be rescued by increasing ribosome biogenesis. Our study reveals that O-GlcNAcylation contributes to the links between protein synthesis and cognitive function in the brain learning center, and provides a useful tool for future dissection of tissue-specific functions of O-GlcNAcylation inDrosophila.
Modelling Disease progression of Multiple Sclerosis in a South Wales Cohort
Authors: Uzochukwu Emeka C , Harding Katharine E , Hrastelj James , Kreft Karim L , Holmans Peter , Jones Lesley , Robertson Neil P , Tallantyre Emma C , Lawton Michael 
Published: September 2023

AbstractObjectivesTo model multiple sclerosis (MS) disease progression and compare disease trajectories by sex, age of onset, and year of diagnosis.Study Design and settingsLongitudinal EDSS scores were collected since 1985 for relapse-onset MS patients at MS clinics in South Wales and modelled using a multilevel model (MLM). The MLM adjusted for baseline covariates (sex, age of onset, year of diagnosis, and disease modifying treatments (DMTs)), and included interactions between baseline covariates and time variables.ResultsThe optimal model was truncated at 30 years after disease onset and excluded EDSS recorded within 3 months of relapse. As expected, older age of onset was associated with faster disease progression at 15 years (effect size (ES): 0.75; CI: 0.63, 0.86; P: <0.001) and female sex progressed more slowly at 15 years (ES: -0.43; CI: -0.68, -0.18; P: <0.001). Patients diagnosed more recently (defined as 2007-2011 and >2011) progressed more slowly than those diagnosed historically (<2006); (ES: -0.46; CI: -0.75, -0.16; P: 0.006) and (ES: -0.95; CI: -1.20, -0.70; P: <0.001), respectively.ConclusionWe present a novel model of MS outcomes, accounting for the nonlinear trajectory of MS and effects of baseline covariates, validating well-known risk factors (sex and age of onset) associated with disease progression. Also, patients diagnosed more recently progressed more slowly than those diagnosed historically.
HILAMA: High-dimensional multi-omic mediation analysis with latent confounding
Authors: Wang Xinbo , Liu Junyuan , Hu Sheng’en Shawn , Liu Zhonghua , Lu Hui , Liu Lin ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2023

AbstractMotivationThe increasingly available multi-omic datasets have posed both new opportunities and challenges to the development of quantitative methods for discovering novel mechanisms in biomedical research. One natural approach to analyzing such datasets is mediation analysis originated from the causal inference literature. Mediation analysis can help unravel the mechanisms through which exposure(s) exert the effect on outcome(s). However, existing methods fail to consider the case where (1) both exposures and mediators are potentially high-dimensional and (2) it is very likely that some important confounding variables are unmeasured or latent; both issues are quite common in practice. To the best of our knowledge, however, no methods have been developed to address these challenges with statistical guarantees.ResultsIn this article, we propose a new method for HIgh-dimensional LAtent-confounding Mediation Analysis, abbreviated as “HILAMA”, that considers both high-dimensional exposures and mediators, and more importantly, the possible existence of latent confounding variables. HILAMA achieves false discovery rate (FDR) control under finite sample size for multiple mediation effect testing. The proposed method is evaluated through extensive simulation experiments, demonstrating its improved stability in FDR control and superior power in finite sample size compared to existing competitive methods. Furthermore, our method is applied to the proteomics-radiomics data from ADNI, identifying some key proteins and brain regions relating to Alzheimer’s disease. The results show that HILAMA can effectively control FDR and provide valid statistical inference for high dimensional mediation analysis with latent confounding variables.AvailabilityThe R packageHILAMAis publicly available athttps://github.com/Cinbo-Wang/HILAMA.Contactcinbo_w@sjtu.edu.cn
Combining Bulk and Single-Cell RNA Sequencing Data to Identify RNA methylation and Autophagy-Related Signatures in Patients with Chronic Obstructive Pulmonary Disease
Authors: Liao Shixia , Zhang Lanying , Wang Yanwen , He Shuangfei , Liu Maomao , Wen Dongmei , Zhou Jian , Liu Yuting , Sun Pengpeng , Wang Qi , Xu Yang , OuYang Yao 
Published: September 2023

AbstractBackgroundChronic Obstructive Pulmonary Disease (COPD) is a heterogeneous lung condition associated with RNA methylation and autophagy. However, the specific autophagy-related genes and RNA methylation regulators involved in COPD development remain unknown.MethodsWe analyzed COPD and non-COPD patients datasets obtained from the Gene Expression Omnibus database, including Tissue Sequencing Transcriptome (bulk-seq) and single-cell sequencing (scRNA-seq) data. Differentially expressed genes (DEGs) were identified through differential genetic analysis using non-COPD bulk-seq data as the control group and COPD samples were used as the experimental group. Animal experiments were conducted to validate the expression of key genes. COPD model mice were exposed to smoke for four months, and lung function and histopathological changes were assessed. The mRNA and protein expression levels ofFTO, IGF2BP2, DDIT3, DNAJB1, andYTHDF3were measured using RT-qPCR and Western blotting, respectively.ResultsWe identifiedFTO, IGF2BP2, andYTHDF3as key methylation genes, along with autophagy hub genesDDIT3andDNAJB1. Animal experiments showed significantly increased mRNA and protein levels ofFTO, YTHDF3and DNAJB1 and significantly decreased levels ofIGF2BP2in lung tissue of COPD mice compared to the control group.ConclusionOur findings suggest thatDDIT3andDNAJB1as autophagy hub genes, along withFTO, IGF2BP2andYTHDF3as RNA methylation genes, may play crucial roles in the development of COPD. These findings, supported by bulk-seq and scRNA-seq data, contribute novel genetic evidence for understanding the epigenetics of COPD.
c-Src induced vascular malformations require localised matrix degradation at focal adhesions
Authors: Essebier Patricia , Schimmel Lilian , Yordanov Teodor , Keyser Mikaela , Yu Alexander , Noordstra Ivar , Hill Brittany , Yap Alpha S. , Stehbens Samantha J. , Lagendijk Anne K. , Gordon Emma J. 
Published: September 2023

AbstractEndothelial cells lining the blood vessel wall communicate intricately with the surrounding extracellular matrix, translating mechanical cues into biochemical signals. Moreover, vessels require the capability to enzymatically degrade the matrix surrounding them, to facilitate vascular expansion. c-Src plays a key role in blood vessel growth, with its loss in the endothelium reducing vessel sprouting and focal adhesion signalling. Here, we show that constitutive activation of c-Src in endothelial cells results in rapid vascular expansion, operating independently of growth factor stimulation or fluid shear stress forces. This is driven by an increase in focal adhesion signalling and size, with enhancement of localised secretion of matrix metalloproteinases responsible for extracellular matrix remodelling. Inhibition of matrix metalloproteinase activity results in a robust rescue of the vascular expansion elicited by heightened c-Src activity. This supports the premise that moderating focal adhesion-related events and matrix degradation can counteract abnormal vascular expansion, with implications for pathologies driven by unusual vascular morphologies.
Naive primary neutrophils play a dual role in the tumor microenvironment
Authors: Babatunde Kehinde Adebayo , Datta Rupsa , Hendrikse Nathan W , Ayuso Jose M , Huttenlocher Anna , Skala Melissa C. , Beebe David J , Kerr Sheena C 
Published: September 2023

ABSTRACTThe tumor microenvironment (TME) is characterized by a network of cancer cells, recruited immune cells and extracellular matrix (ECM) in a hypoxic microenvironment. However, the specific role of neutrophils during tumor development, and their interactions with other immune cells is still not well understood. Thus, there is a need to investigate the interaction between primary neutrophils and natural killer cells and the resulting effects on tumor development. Here we use both standard well plate culture and an under oil microfluidic (UOM) assay with an integrated extracellular cell matrix (ECM) bridge to elucidate how naive primary neutrophils respond to both patient derived tumor cells and tumor cell lines. Our data demonstrated that both patient derived head and neck squamous cell carcinoma (HNSCC) tumor cells and MDA-MB-231 breast cancer cells trigger cluster formation in neutrophils, and the swarm of neutrophils restricts tumor invasion through the generation of reactive oxygen species (ROS) and neutrophil extracellular trap (NETs) release within the neutrophil cluster. However, we also observed that the presence of neutrophils downregulates granzyme B in NK-92 cells and the resulting NETs can obstruct NK cells from penetrating the tumor massin vitrosuggesting a dual role for neutrophils in the TME. Further, using label-free optical metabolic imaging (OMI) we observed changes in the metabolic activities of primary neutrophils during the different swarming phases when challenged with tumor cells. Finally, our data demonstrates that neutrophils in direct contact, or in close proximity, with tumor cells exhibit greater metabolic activities (lower nicotinamide adenine dinucleotide phosphate (NAD(P)H) mean lifetime) compared to non-contact neutrophils.
The SARS-CoV-2 nucleoprotein associates with anionic lipid membranes
Authors: Dutta Mandira , Su Yuan , Voth Gregory A. , Stahelin Robert V. 
Published: September 2023

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a lipid-enveloped virus that acquires its lipid bilayer from the host cell it infects. SARS-CoV-2 can spread from cell to cell or from patient to patient by undergoing assembly and budding to form new virions. The assembly and budding of SARS-CoV-2 is mediated by several structural proteins known as envelope (E), membrane (M), nucleoprotein (N) and spike (S), which can form virus-like particles (VLPs) when co-expressed in mammalian cells. Assembly and budding of SARS-CoV-2 from the host ER-Golgi intermediate compartment is a critical step in the virus acquiring its lipid bilayer. To date, little information is available on how SARS-CoV-2 assembles and forms new viral particles from host membranes. In this study, we find the N protein can strongly associate with anionic lipids including phosphoinositides and phosphatidylserine. Moreover, lipid binding is shown to occur in the N protein C-terminal domain, which is supported by extensivein silicoanalysis. Anionic lipid binding occurs for both the free and N oligomeric forms suggesting N can associate with membranes in the nucleocapsid form. Herein we present a lipid-dependent model based onin vitro, cellular andin silicodata for the recruitment of N to M assembly sites in the lifecycle of SARS-CoV-2.
Human HYPOMAP: A comprehensive spatio-cellular map of the human hypothalamus
Authors: Tadross John A. , Steuernagel Lukas , Dowsett Georgina K.C. , Kentistou Katherine A. , Lundh Sofia , Porniece-Kumar Marta , Klemm Paul , Rainbow Kara , Hvid Henning , Kania Katarzyna , Polex-Wolf Joseph , Bjerre-Knudsen Lotte , Pyke Charles , Perry John R. B. , Lam Brian Y.H. , Brüning Jens C. , Yeo Giles S.H. 
Published: September 2023

AbstractThe hypothalamus is a brain region that plays a key role in coordinating fundamental biological functions. However, our understanding of the underlying cellular components and circuitry, have, until recently, emerged primarily from rodent studies. Here, we combine a single-nucleus sequencing database of 433,369 human hypothalamic cells, with spatial transcriptomics, to present a comprehensive spatio-cellular transcriptional map of the human hypothalamus, the ‘HYPOMAP’. Analysing hypothalamic leptin melanocortin pathway neuronal populations that play a role in appetite control, we identify spatially distinct populations of arcuate nucleusPOMCandAGRPneurons, and their receptorsMC3RandMC4R. Next, we map the cells expressing incretin receptors, targets of the new generation of anti-obesity medications, and uncover transcriptionally distinctGLP1RandGIPR-expressing cellular populations. Finally, out of the 458 hypothalamic cell types in HYPOMAP, we find 182 neuronal clusters are significantly enriched in expression of BMI GWAS genes. This enrichment is driven by 375 ‘effector’ genes, with rare deleterious variants in 6 of these;MC4R,PCSK1,POMC,CALCR,BSNandCORO1A, the last of which has previously not been linked to obesity; being significantly associated with changes in BMI at the population level. Thus, the HYPOMAP provides a detailed atlas of the human hypothalamus in a spatial context, and serves as an important resource to identify novel druggable targets for treating a wide range of conditions, including reproductive, circadian, and metabolic disorders.
The resilience of German regions facing the crisis in 2008/2009: the effects of innovation, specialisation, qualifications and sectoral structure
Authors: Celebioglu Fatih , Brenner Thomas 
Published: September 2023

Purpose
The purpose of this paper is to explain the effects of innovation, specialisation, qualifications and sectoral structure on the resilience of German regions (municipal level) facing the Great Recession in 2008/2009.

Design/methodology/approach
To calculate the effects of various variables on the resilience of German regions against the Great Recession, the authors use quantile regressions. To measure resilience, the authors create a number of indexes representing different parts of the economy: resistance performance index, recovery performance index, shift-share resistance index, shift-share recovery index, manufacturing resistance index, manufacturing recovery index, service resistance index and service recovery index.

Findings
The results of this study confirm that locations with employment growth before the crisis and with a good industry structure show better employment dynamics during and after the crisis. The authors find evidence for positive relationship between innovativeness, qualification, the share of the service sector, specialisation and resistance. The authors obtain positive results for related variety and both resistance and recovery. The share of the manufacturing sector only shows a positive relationship with recovery.

Originality/value
The authors expand the existing literature in three aspects: First, instead of using regions as observation units, the authors conduct the analyses on the basis of municipalities and their surroundings. By doing so, the authors reduce the modifiable area unit problem because the authors do not rely on regions defined for administrative reasons. Second, the authors apply quantile regressions to detect nonlinear effects. Third, in addition to the resilience of the whole economy, the authors also study the resilience of the manufacturing and service sectors separately and examine the resilience of the local shift effect.
Commodity prices and business cycles in small open economies: the role of news shocks
Authors: Farias Cleyton , Silva Marcelo 
Published: September 2023

PurposeThe authors explore the hypothesis that some movements in commodity prices are anticipated (news shocks) and can trigger aggregate fluctuations in small open emerging economies. This paper aims to discuss the aforementioned objective.Design/methodology/approachThe authors build a multi-sector dynamic stochastic general equilibrium model with endogenous commodity production. There are five exogenous processes: a country-specific interest rate shock that responds to commodity price fluctuations, a productivity (TFP) shock for each sector and a commodity price shock. Both TFP and commodity price shocks are composed of unanticipated and anticipated components.FindingsThe authors show that news shocks to commodity prices lead to higher output, investment and consumption, and a countercyclical movement in the trade-balance-to-output ratio. The authors also show that commodity price news shocks explain about 24% of output aggregate fluctuations in the small open economy.Practical implicationsGiven the importance of both anticipated and unanticipated commodity price shocks, policymakers should pay attention to developments in commodity markets when designing policies to attenuate the business cycles. Future research should investigate the design of optimal fiscal and monetary policies in SOE subject to news shocks in commodity prices.Originality/valueThis paper contributes to the knowledge of the sources of fluctuations in emerging economies highlighting the importance of a new source: news shocks in commodity prices.