bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transitional alveolar epithelial cells and microenvironmental stiffness synergistically drive fibroblast activation in three-dimensional hydrogel lung models
Authors: Caracena Thomas , Blomberg Rachel , Hewawasam Rukshika S. , Riches David W.H. , Magin Chelsea M. 
Published: May 2022

AbstractIdiopathic pulmonary fibrosis (IPF) is a devastating lung disease that progressively and irreversibly alters the lung parenchyma, eventually leading to respiratory failure. The study of this disease has been historically challenging due to the myriad of complex processes that contribute to fibrogenesis and the inherent difficulty in accurately recreating the human pulmonary environmentin vitro. Here, we describe a poly(ethylene glycol) PEG hydrogel-based three-dimensional model for the co-culture of primary murine pulmonary fibroblasts and alveolar epithelial cells that reproduces the micro-architecture, cell placement, and mechanical properties of healthy and fibrotic lung tissue. Co-cultured cells retained normal levels of viability up to at least three weeks and displayed differentiation patterns observedin vivoduring IPF progression. Interrogation of protein and gene expression within this model showed that myofibroblast activation required both extracellular mechanical cues and the presence of transitional epithelial cells. Differences in gene expression indicated that cellular co-culture induced TGF-β signaling and proliferative gene expression, while microenvironmental stiffness upregulated the expression of genes related to cell-ECM interactions. This biomaterial-based cell culture system serves as a significant step forward in the accurate recapitulation of human lung tissuein vitro, and highlights the need to incorporate multiple factors that work together synergisticallyin vivointo models of lung biology of health and disease.
LKB1 is the gatekeeper of carotid body chemo-sensing and the hypoxic ventilatory response
Authors: MacMillan Sandy , Holmes Andrew P. , Dallas Mark L. , Mahmoud Amira D. , Shipston Michael J. ,   the late Chris Peers, Hardie D. Grahame , Kumar Prem , Evans A. Mark 
Published: May 2022

AbstractThe hypoxic ventilatory response (HVR) is critical to breathing and thus oxygen supply to the body and is primarily mediated by the carotid bodies. Here we reveal that carotid body afferent discharge during hypoxia and hypercapnia is determined by the expression of Liver Kinase B1 (LKB1), the principal kinase that activates the AMP-activated protein kinase (AMPK) during metabolic stresses. Conversely, conditional deletion in catecholaminergic cells of AMPK had no effect on carotid body responses to hypoxia or hypercapnia. By contrast, the HVR was attenuated by LKB1 and AMPK deletion. However, in LKB1 knockouts hypoxia evoked hypoventilation, apnoea and Cheyne-Stokes-like breathing, while only hypoventilation and apnoea were observed after AMPK deletion. We therefore identify LKB1 as an essential regulator of carotid body chemosensing and uncover a divergence in dependency on LKB1 and AMPK between the carotid body on one hand and the HVR on the other.
Drosophila Rif1 is critical for repair following P-element excision and influences pathway choice at double-strand breaks
Authors: Blanch Justin R. , Krishnamurthy Manan , Zuckerman Jacob T. , McVey Mitch 
Published: May 2022

AbstractRif1 plays important roles in the repair of DNA double-strand breaks in multiple organisms. In mammals, RIF1 promotes non-homologous end joining and suppresses homologous recombination by interacting with 53BP1 to inhibit resection. In Saccharomyces cerevisiae, Rif1 directly binds DNA to inhibit resection and promote non-homologous end-joining. Yeast Rif1 can also facilitate long-range resection and promote single-strand annealing. Since it is not clear if Rif1 regulates resection-mediated pathway choice in other eukaryotes, we explored the role of Rif1 in double-strand break repair in Drosophila melanogaster. We found that rif1 mutants are not sensitive to ionizing radiation or hydroxyurea, demonstrating that it is not essential for the resolution of DNA damage in Drosophila. However, we show that rif1 null mutants are largely unable to repair a specific type of double-strand break that is induced upon the excision of a P-element transposon. Furthermore, assessment of repair pathway choice at I-SceI-induced breaks revealed Rif1 suppresses homologous recombination and promotes single-strand annealing. Collectively, our findings illustrate Drosophila Rif1 shares functions with both its yeast and mammalian counterparts and serves a unique role in repairing P-element-induced double-strand breaks.
Dissociation of reliability, heritability, and predictivity in coarse- and fine-scale functional connectomes during development
Authors: Busch Erica L. , Rapuano Kristina M. , Anderson Kevin M. , Rosenberg Monica D. , Watts Richard , Casey BJ , Haxby James V. , Feilong Ma 
Published: May 2022

AbstractThe functional connectome supports information transmission through the brain at various spatial scales, from exchange between broad cortical regions to finer–scale, vertex–wise connections that underlie specific information processing mechanisms. In adults, while both the coarse- and fine-scale functional connectomes predict cognition, the fine-scale can predict up to twice the variance as the coarse-scale functional connectome. Yet, past brain-wide association studies, particularly using large developmental samples, focus on the coarse connectome to understand the neural underpinnings of individual differences in cognition. Using a large cohort of children (age 9 – 10 years;n= 1,115 individuals, both sexes, 50% female, including 170 monozygotic and 219 dizygotic twin pairs and 337 unrelated individuals), we examine the reliability, heritability, and behavioral relevance of resting-state functional connectivity computed at different spatial scales. We use connectivity hyperalignment to improve access to reliable fine-scale (vertex–wise) connectivity information and compare the fine-scale connectome with the traditional parcel–wise (coarse scale) functional connectomes. Though individual differences in the fine-scale connectome are more reliable than those in the coarse-scale, they are less heritable. Further, the alignment and scale of connectomes influence their ability to predict behavior, whereby some cognitive traits are equally well predicted by both connectome scales, but other, less heritable cognitive traits are better predicted by the fine-scale connectome. Together, our findings suggest there are dissociable individual differences in information processing represented at different scales of the functional connectome which, in turn, have distinct implications for heritability and cognition.Significance statementYears of human magnetic resonance imaging (MRI) research demonstrate that individual variability in resting-state functional connectivity relates to genetics and cognition. However, the various spatial scales where individual differences in connectivity could occur have yet to be considered in childhood brain– behavior association studies. Here, we use novel machine learning approaches to examine the reliability, heritability, and behavioral relevance of different spatial scales of the resting-state functional connectome during childhood. We show that broad features of the connectome are strongly related to heritability, whereas fine details are more reliable and strongly associated with neurocognitive performance. These data indicate that reliable, heritable, and behaviorally–relevant individual differences exist at dissociable scales of the functional connectome.
Acute COG inactivation unveiled its immediate impact on Golgi and illuminated the nature of intra-Golgi recycling vesicles
Authors: Sumya Farhana Taher , Pokrovskaya Irina D. , D’Souza Zinia , Lupashin Vladimir V. 
Published: May 2022

AbstractConserved Oligomeric Golgi (COG) complex controls Golgi trafficking and glycosylation, but the precise COG mechanism is unknown. The auxin-inducible acute degradation system was employed to investigate initial defects resulting from COG dysfunction. We found that acute COG inactivation caused a massive accumulation of COG-dependent (CCD) vesicles that carry the bulk of Golgi enzymes and resident proteins. v-SNAREs (GS15, GS28) and v-tethers (giantin, golgin84, and TMF1) were relocalized into CCD vesicles, while t-SNAREs (STX5, YKT6), t-tethers (GM130, p115), and most of Rab proteins remained Golgi-associated. Airyscan microscopy and velocity gradient analysis revealed that different Golgi residents are segregated into different populations of CCD vesicles. Acute COG depletion significantly affected three Golgi-based vesicular coats- COPI, AP1, and GGA, suggesting that COG uniquely orchestrates tethering of multiple types of intra-Golgi CCD vesicles produced by different coat machineries. This study provided the first detailed view of primary cellular defects associated with COG dysfunction in human cells.
A humanized yeast model reveals dominant-negative properties of neuropathy-associated alanyl-tRNA synthetase mutations
Authors: Meyer-Schuman Rebecca , Marte Sheila , Smith Tyler J. , Feely Shawna M.E. , Kennerson Marina , Nicholson Garth , Shy Mike E. , Koutmou Kristin S. , Antonellis Anthony 
Published: May 2022

ABSTRACTAminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes that ligate tRNA molecules to their cognate amino acids. Heterozygosity for missense variants or small in-frame deletions in five ARS genes causes axonal peripheral neuropathy, a disorder characterized by impaired neuronal function in the distal extremities. These variants reduce enzyme activity without significantly decreasing protein levels and reside in genes encoding homo-dimeric enzymes. These observations raise the possibility of a dominant-negative effect, in which non-functional mutant ARS subunits dimerize with wild-type ARS subunits and reduce overall ARS activity below 50%, breaching a threshold required for peripheral nerve axons. To test for these dominant-negative properties, we developed a humanized yeast assay to co-express pathogenic human alanyl-tRNA synthetase (AARS1) mutations with wild-type human AARS1. We show that multiple loss-of-function, pathogenic AARS1 variants repress yeast growth in the presence of wild-type human AARS1. This growth defect is rescued when these variants are placed in cis with a mutation that reduces dimerization with the wild-type subunit, demonstrating that the interaction between mutant AARS1 and wild-type AARS1 is responsible for the repressed growth. This demonstrates that neuropathy-associated AARS1 variants exert a dominant-negative effect, which supports a common, loss-of-function mechanism for ARS-mediated dominant peripheral neuropathy.
ReSurveyGermany: Vegetation-plot time-series over the past hundred years in Germany
Authors: Jandt Ute , Bruelheide Helge , Berg Christian , Bernhardt-Römermann Markus , Blüml Volker , Bode Frank , Dengler Jürgen , Diekmann Martin , Dierschke Hartmut , Doerfler Inken , Döring Ute , Dullinger Stefan , Härdtle Werner , Haider Sylvia , Heinken Thilo , Horchler Peter , Jansen Florian , Kudernatsch Thomas , Kuhn Gisbert , Lindner Martin , Matesanz Silvia , Metze Katrin , Meyer Stefan , Müller Frank , Müller Norbert , Naaf Tobias , Peppler-Lisbach Cord , Poschlod Peter , Roscher Christiane , Rosenthal Gert , Rumpf Sabine B. , Schmidt Wolfgang , Schrautzer Joachim , Schwabe Angelika , Schwartze Peter , Sperle Thomas , Stanik Nils , Stroh Hans-Georg , Storm Christian , Voigt Winfried , von Heßberg Andreas , von Oheimb Goddert , Wagner Eva-Rosa , Wegener Uwe , Wesche Karsten , Wittig Burghard , Wulf Monika 
Published: May 2022

AbstractVegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow calculating temporal biodiversity change at the community scale and reach back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century.
Robust and Versatile Arrayed Libraries for Human Genome-Wide CRISPR Activation, Deletion and Silencing
Authors: Yin Jiang-An , Frick Lukas , Scheidmann Manuel C. , Liu Tingting , Trevisan Chiara , Dhingra Ashutosh , Spinelli Anna , Wu Yancheng , Yao Longping , Vena Dalila Laura , Knapp Britta , Cecco Elena De , Ging Kathi , Armani Andrea , Oakeley Edward , Nigsch Florian , Jenzer Joel , Haegele Jasmin , Pikusa Michal , Täger Joachim , Rodriguez-Nieto Salvador , Guo Jingjing , Bouris Vangelis , Ribeiro Rafaela , Baroni Federico , Bedi Manmeet Sakshi , Berry Scott , Losa Marco , Hornemann Simone , Kampmann Martin , Pelkmans Lucas , Hoepfner Dominic , Heutink Peter , Aguzzi Adriano 
Published: May 2022

AbstractArrayed CRISPR libraries extend the scope of gene-perturbation screens but require large numbers of efficacious sgRNA-expressing vectors. Using a newly invented liquid-phase plasmid cloning methodology, we constructed genome-wide arrayed libraries for human gene ablation (19,936 plasmids), activation, and epigenetic silencing (22,442 plasmids). At least 76% of each plasmid preparation encoded an intact array of 4 non-overlapping sgRNAs designed to tolerate most human DNA polymorphisms. We achieved perturbation efficacies of 75-99%, 76-92% and up to 10,000x in deletion, silencing and activation experiments, respectively. Upon conversion into massively parallel lentiviral vectors, an arrayed activation screen of 1,634 human transcription factors yielded 11 novel regulators of the cellular prion protein PrPC. Furthermore, a screen using a pooled version of the ablation library identified 5 novel modifiers of autophagy that went undetected with either of two 1sgRNA libraries. The CRISPR libraries described here represent a powerful resource for the targeted perturbation of human protein-coding genes.
Peripersonal encoding of forelimb proprioception in the mouse somatosensory cortex
Authors: Alonso Ignacio , Scheer Irina , Palacio-Manzano Mélanie , Frézel-Jacob Noémie , Philippides Antoine , Prsa Mario 
Published: May 2022

AbstractConscious perception of limb movements depends on proprioceptive neural responses in the somatosensory cortex. In contrast to tactile sensations, proprioceptive cortical coding is barely studied in the mammalian brain and practically non-existent in rodent research. To understand the cortical representation of this important sensory modality we developed a passive forelimb displacement paradigm in behaving mice and also trained them to perceptually discriminate where their limb is moved in space. We delineated, for the first time, the rodent proprioceptive cortex with wide-field calcium imaging and optogenetic silencing experiments during awake behavior. Our results reveal that proprioception is represented in both sensory and motor cortical areas. In addition, behavioral measurements and responses of layer 2/3 neurons imaged with two-photon microscopy reveal that passive limb movements are both perceived and encoded in the mouse cortex as a spatial direction vector that interfaces the limb with the body’s peripersonal space.
Distinct antigenic properties of the SARS-CoV-2 Omicron lineages BA.4 and BA.5
Authors: Willett Brian J. , Kurshan Ashwini , Thakur Nazia , Newman Joseph , Manali Maria , Tyson Grace , Logan Nicola , Murcia Pablo R. , Snell Luke B. , Edgeworth Jonathan D. , Zhou Jie , Sukhova Ksenia , Amirthalingam Gayatri , Brown Kevin , Charleston Bryan , Malim Michael H. , Thomson Emma C. , Barclay Wendy S. , Bailey Dalan , Doores Katie J. , Peacock Thomas P. 
Published: May 2022

AbstractOver the course of the pandemic variants have arisen at a steady rate. The most recent variants to emerge, BA.4 and BA.5, form part of the Omicron lineage and were first found in Southern Africa where they are driving the current wave of infection.In this report, we perform an in-depth characterisation of the antigenicity of the BA.4/BA.5 Spike protein by comparing sera collected post-vaccination, post-BA.1 or BA.2 infection, or post breakthrough infection of vaccinated individuals with the Omicron variant. In addition, we assess sensitivity to neutralisation by commonly used therapeutic monoclonal antibodies.We find sera collected post-vaccination have a similar ability to neutralise BA.1, BA.2 and BA.4/BA.5. In contrast, in the absence of vaccination, prior infection with BA.2 or, in particular, BA.1 results in an antibody response that neutralises BA.4/BA.5 poorly. Breakthrough infection with Omicron in vaccinees leads to a broad neutralising response against the new variants. The sensitivity of BA.4/BA.5 to neutralisation by therapeutic monoclonal antibodies was similar to that of BA.2.These data suggest BA.4/BA.5 are antigenically distinct from BA.1 and, to a lesser extent, BA.2. The enhanced breadth of neutralisation observed following breakthrough infection with Omicron suggests that vaccination with heterologous or multivalent antigens may represent viable strategies for the development of cross-neutralising antibody responses.
Lipidic cubic phase serial femtosecond crystallography structure of a photosynthetic reaction centre
Authors: Båth Petra , Banacore Analia , Börjesson Per , Bosman Robert , Wickstrand Cecilia , Safari Cecilia , Dods Robert , Ghosh Swagatha , Dahl Peter , Ortolani Giorgia , Björg Ulfarsdottir Tinna , Hammarin Greger , García Bonete María-José , Vallejos Adams , Ostojić Lucija , Edlund Petra , Linse Johanna-Barbara , Andersson Rebecka , Nango Eriko , Owada Shigeki , Tanaka Rie , Tono Kensuke , Joti Yasumasa , Nureki Osamu , Luo Fangjia , James Daniel , Nass Karol , Johnson Philip J. M. , Knopp Gregor , Ozerov Dmitry , Cirelli Claudio , Milne Christopher , Iwata So , Brändén Gisela , Neutze Richard 
Published: May 2022

Serial crystallography is a rapidly growing method that can yield structural insights from microcrystals that were previously considered to be too small to be useful in conventional X-ray crystallography. Here, conditions for growing microcrystals of the photosynthetic reaction centre of Blastochloris viridis within a lipidic cubic phase (LCP) crystallization matrix that employ a seeding protocol utilizing detergent-grown crystals with a different crystal packing are described. LCP microcrystals diffracted to 2.25 Å resolution when exposed to XFEL radiation, which is an improvement of 0.15 Å over previous microcrystal forms. Ubiquinone was incorporated into the LCP crystallization media and the resulting electron density within the mobile QB pocket is comparable to that of other cofactors within the structure. As such, LCP microcrystallization conditions will facilitate time-resolved diffraction studies of electron-transfer reactions to the mobile quinone, potentially allowing the observation of structural changes associated with the two electron-transfer reactions leading to complete reduction of the ubiquinone ligand.
COVID-19 catastrophes and stock market liquidity: evidence from technology industry of four biggest ASEAN capital market
Authors: Priscilla Sherin , Hatane Saarce Elsye , Tarigan Josua 
Published: May 2022

PurposeThis study examines the influence of various COVID-19 catastrophes variables on the stock market liquidity, considering the market depth and market tightness in the technology industry of the four biggest ASEAN capital markets.Design/methodology/approachThe study utilised the panel data regression analysis obtained from 177 listed technology companies across the four ASEAN countries from March 2, 2020 to June 30, 2021 using the random effect and weighted least squares. The study also supported the result with robustness test, implementing the quantile regression to further present companies' segmentation within the variables.FindingsThe regression results indicate that daily growth COVID-19 confirmed cases and stringency that adversely impacted the stock market liquidity. Confirmed deaths were also found to have a detrimental effect on the stock market liquidity. On the other hand, recoveries and vaccination of COVID-19 enhance the stock market liquidity to escalate.Research limitations/implicationsThe study affirms that stock market liquidity is bound to be driven by the COVID-19 variables, but only to be limited to the technology industry observed in four major ASEAN capital markets. Awareness by investors and government could be shifted towards the rise of confirmed cases, recoveries, vaccination and stringency as it improves the liquidity of capital market in aggregate. However, rise of confirmed deaths negatively affect the liquidity. All in all, government and stock market regulator should promote transparency to boost investors' confidence in trading.Originality/valueThis study initiates the investigation in the four biggest ASEAN capital markets, particularly in the technology industry, regarding the COVID-19 catastrophes and stock market liquidity in terms of both market depth and market tightness. Further, this study enriches the impact of COVID-19 by taking the recovery cases and vaccination of COVID-19 as additional consideration.
Prediction method of motor magnetic field based on improved Linknet model
Authors: Jin Liang , Liu Yuankai , Yang Qingxin , Zhang Chuang , Liu Suzhen 
Published: May 2022

Purpose
Under the condition of small data set, a prediction model of motor magnetic field is established based on deep learning method. This paper aims to complete the magnetic field prediction quickly and accurately.

Design/methodology/approach
An improved Linknet model is proposed to predict the motor magnetic field. This is a digital twin technology, which can predict the function values of other points according to the function values of typical sampling points. The results of magnetic field distribution are represented by color images. By predicting the pixels of the image, the corresponding magnetic field distribution is obtained. The model not only considers the correlation between pixels but also retains the spatial information in the original input image and can well learn the mapping relationship between motor structure and magnetic field.

Findings
The model can speed up the calculation while ensuring the accuracy and has obvious advantages in large-scale calculation and real-time simulation.

Originality/value
Under the condition of small data set, the model can well learn the mapping relationship between motor structure and magnetic field, so as to complete the magnetic field prediction quickly and accurately. In the future, according to the characteristics of magnetic field distribution, it will lay a foundation for solving the problems of rapid optimization, real-time simulation and physical field control of electrical equipment.