bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Relationship Between Molecular Rejection and Parenchymal Injury in Heart Transplant Biopsies
Authors: Madill-Thomsen Katelynn S. , Reeve Jeff , Aliabadi-Zuckermann Arezu , Cadeiras Martin , Crespo-Leiro Marisa G. , Depasquale Eugene C. , Deng Mario , Goekler Johannes , Kim Daniel H. , Kobashigawa Jon , Macdonald Peter , Potena Luciano , Shah Keyur , Stehlik Josef , Zuckermann Andreas , Halloran Philip F. 
Published: August 2022

Background.
The INTERHEART study (ClinicalTrials.gov #NCT02670408) used genome-wide microarrays to detect rejection in endomyocardial biopsies; however, many heart transplants with no rejection have late dysfunction and impaired survival. We used the microarray measurements to develop a molecular classification of parenchymal injury.

Methods.
In 1320 endomyocardial biopsies from 645 patients previously studied for rejection-associated transcripts, we measured the expression of 10 injury-induced transcript sets: 5 induced by recent injury; 2 reflecting macrophage infiltration; 2 normal heart transcript sets; and immunoglobulin transcripts, which correlate with time. We used archetypal clustering to assign injury groups.

Results.
Injury transcript sets correlated with impaired function. Archetypal clustering based on the expression of injury transcript sets assigned each biopsy to 1 of 5 injury groups: 87 Severe-injury, 221 Late-injury, and 3 with lesser degrees of injury, 376 No-injury, 526 Mild-injury, and 110 Moderate-injury. Severe-injury had extensive loss of normal transcripts (dedifferentiation) and increase in macrophage and injury-induced transcripts. Late-injury was characterized by high immunoglobulin transcript expression. In Severe- and Late-injury, function was depressed, and short-term graft failure was increased, even in hearts with no rejection. T cell–mediated rejection almost always had parenchymal injury, and 85% had Severe- or Late-injury. In contrast, early antibody-mediated rejection (AMR) had little injury, but late AMR often had the Late-injury state.

Conclusions.
Characterizing heart transplants for their injury state provides new understanding of dysfunction and outcomes and demonstrates the differential impact of T cell–mediated rejection versus AMR on the parenchyma. Slow deterioration from AMR emerges as a major contributor to late dysfunction.
Design, implementation, and functional validation of a new generation of microneedle 3D high-density CMOS multi-electrode array for brain tissue and spheroids
Authors: Mapelli Lisa , Dubochet Olivier , Tedesco Mariateresa , Sciacca Giacomo , Ottaviani Alessandra , Monteverdi Anita , Battaglia Chiara , Tritto Simona , Cardot Francis , Surbled Patrick , Schildknecht Jan , Gandolfo Mauro , Imfeld Kilian , Cervetto Chiara , Marcoli Manuela , D’Angelo Egidio , Maccione Alessandro 
Published: August 2022

AbstractIn the last decades, planar multi-electrode arrays (MEAs) have been widely used to record activity from in vitro neuronal cell cultures and tissue slices. Though successful, this technique bears some limitations, particularly relevant when applied to three-dimensional (3D) tissue, such as brain slices, spheroids or organoids. For example, planar MEAs signals are informative on just one side of a 3D-organized structure. This limits the interpretation of the results in terms of network functions in a complex structured and hyperconnected brain tissue. Moreover, the side in contact with the MEAs often shows lower oxygenation rates and related vitality issues. To overcome these problems, we empowered a CMOS high-density multi-electrode array (HD-MEA) with thousands of microneedles (μneedles) of 65-90 μm height, able to penetrate and record in-tissue signals, providing for the first time a 3D HD-MEA chip. We propose a CMOS-compatible fabrication process to produce arrays of μneedles of different widths mounted on large pedestals to create microchannels underneath the tissue. By using cerebellar and cortico-hippocampal slices as a model, we show that the μneedles efficiently penetrate the 3D tissue while the microchannels allow the flowing of maintenance solutions to increase tissue vitality in the recording sites. These improvements are reflected by the increase in electrodes sensing capabilities, the number of sampled neuronal units (compared to matched planar technology), and the efficiency of compound effects. Importantly, each electrode can also be used to stimulate the tissue with optimal efficiency due to the 3D structure. Furthermore, we demonstrate how the 3D HD-MEA can efficiently penetrate and get outstanding signals from in vitro 3D cellular models as brain spheroids. In conclusion, we describe a new recording device characterized by the highest spatio-temporal resolution reported for a 3D MEA and significant improvements in the quality of recordings, with a high signal-to-noise ratio and improved tissue vitality. The applications of this game-changing technique are countless, opening unprecedented possibilities in the neuroscience field and beyond.
L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits
Authors: Lucente Jacopo Di , Tena Jennyfer , Mendiola Ulises R. , Chen Xi , Lebrilla Carlito B. , Maezawa Izumi , Jin Lee-Way 
Published: August 2022

AbstractWe identified a novel signaling function of L-fucose, a structurally unique monosaccharide. We showed that L-fucose enhanced excitatory neurotransmission and long-term potentiation (LTP) in Schaffer-collateral-CA1 synapses. L-fucose was released by neurons in an activity- and store-dependent manner, and induced rapid signaling changes to enhance presynaptic release. Such effects required L-fucose metabolism through the salvage pathway driven by fucokinase (FUK). Thus, L-fucose could be the first described monosaccharide neuromodulator affecting a metabolic-signaling mechanism. Human Alzheimer’s disease (AD) and 5xFAD mouse brains showed signs of fucose hypometabolism with impaired L-fucose signaling. Such abnormalities could be corrected by exogenous L-fucose, exemplified by rectification of LTPdeficits in 5xFAD hippocampus. Dietary L-fucose supplement, which increased cerebral free L-fucose levels and upregulated FUK to drive the salvage pathway, mitigated synaptic and behavioral deficits of 5xFAD mice. Our data reveals a therapeutic potential of oral L-fucose for AD, which is safe and easy to comply with.
Genome-wide association analysis of hyperspectral reflectance data to dissect growth-related traits genetic architecture in maize under inoculation with plant growth-promoting bacteria
Authors: Yassue Rafael Massahiro , Galli Giovanni , Chen Chun-Peng James , Fritsche-Neto Roberto , Morota Gota 
Published: August 2022

AbstractPlant growth-promoting bacteria (PGPB) may be of use for increasing crop yield and plant resilience to biotic and abiotic stressors. Using hyperspectral reflectance data to assess growth-related traits may shed light on the underlying genetics as such data can help assess biochemical and physiological traits. This study aimed to integrate hyperspectral reflectance data with genome-wide association analyses to examine maize growth-related traits under PGPB inoculation. A total of 360 inbred maize lines with 13,826 single nucleotide polymorphisms (SNPs) were evaluated with and without PGPB inoculation; 150 hyperspectral wavelength reflectances at 386–1,021 nm and 131 hyperspectral indices were used in the analysis. Plant height, stalk diameter, and shoot dry mass were measured manually. Overall, hyperspectral signatures produced similar or higher genomic heritability estimates than those of manually measured phenotypes, and they were genetically correlated with manually measured phenotypes. Furthermore, several hyperspectral reflectance values and spectral indices were identified by genome-wide association analysis as potential markers for growthrelated traits under PGPB inoculation. Eight SNPs were detected, which were associated with manually measured and hyperspectral phenotypes. Moreover, the hyperspectral phenotypes were associated with genes previously reported as candidates for nitrogen uptake efficiency, tolerance to abiotic stressors, and kernel size. In addition, a Shiny web application was developed to explore multi-phenotype genome-wide association results interactively. Taken together, our results demonstrate the usefulness of hyperspectral-based phenotyping for studying maize growth-related traits in response to PGPB inoculation.
Automatic detection, identification and counting of anguilliform fish using in situ acoustic camera data: development of a cross-camera morphological analysis approach
Authors: Le Quinio Azénor , De Oliveira Eric , Girard Alexandre , Guillard Jean , Roussel Jean-Marc , Zaoui Fabrice , Martignac François 
Published: August 2022

AbstractAcoustic cameras are increasingly used in monitoring studies of diadromous fish populations, even though analyzing them is time-consuming. In complex in situ contexts, anguilliform fish may be especially difficult to identify automatically using acoustic camera data because the undulation of their body frequently results in fragmented targets. Our study aimed to develop a method based on a succession of computer vision techniques, in order to automatically detect, identify and count anguilliform fish using data from multiple models of acoustic cameras. Indeed, several models of cameras, owning specific technical characteristics, are used to monitor fish populations, causing major differences in the recorded data shapes and resolutions. The method was applied to two large datasets recorded at two distinct monitoring sites with populations of European eels with different length distributions. The method yielded promising results for large eels, with more than 75% of eels automatically identified successfully using datasets from ARIS and BlueView cameras. However, only 42% of eels shorter than 60 cm were detected, with the best model performances observed for detection ranges of 4-9 m. Although improvements are required to compensate for fish-length limitations, our cross-camera method is promising for automatically detecting and counting large eels in long-term monitoring studies in complex environments.
CD98 is critical for a conserved inflammatory response to diverse injury stimuli relevant to IPF exacerbations and COVID pneumonitis
Authors: Stylianou Panayiota , Rushwan Sara , Wang Wei , Miah M. Azim , Darweesh Omeed , Mackinnon Alison , Roach Katy M. , Hitchman Charles J. , Gonchar Oksana , Thorpe Stephen , Harris Christopher , Haigh Richard , Richards David F , Snetkov Vladimir , Beasley Jessica , Cleary Simon J , Barer Michael , Ward Jeremy PT , Rooney Claire , McCaughan Frank , Bradding Peter , Beale Richard , Knight Martin M , Sethi Tariq , Gooptu Bibek 
Published: August 2022

AbstractProgressive fibrosing interstitial lung diseases (PFILDs) cause substantial morbidity and mortality. Antifibrotic agents slow progression, but most of the clinical need remains unmet. The archetypal PFILD is idiopathic pulmonary fibrosis (IPF). Chronic progression is driven by transforming growth factor (TGF-)β1 signalling. It is punctuated by inflammatory flares known as acute exacerbations (AE-IPF), which are associated with accelerated decline and high mortality. We hypothesized that acute injury responses underlying exacerbations and the mechanisms of chronic fibrosis overlap at the molecular level, via a cell surface assembly nucleated by galectin-3 that we term the ‘gal-3-fibrosome’. We focused upon a putative pro-inflammatory galectin-3 ligand, the CD98:integrin complex. Our data indicate CD98 and β1-integrin co-localise with galectin-3 within epithelial cells in IPF lung tissue, and within 40 nm in human lung tissue treated with TGF-β1 compared to controls. CD98 is required for interleukin (IL-)6 and IL-8 responses to biochemical and biophysical conditions mimicking stimuli of AE-IPF in vivo, ex vivo and in cells, and for an interstitial neutrophilic response in a mouse model. We demonstrate this pathway progresses via intracellular influx of Ca2+ mediated by TRPV4, and NF-κB activation, operating in positive feedback. Lastly we show the CD98- and galectin-3-dependence of IL-6 and IL-8 responses to the SARS-CoV-2 spike protein receptor binding domain and the conservation of this response pattern between lung epithelial cells and monocyte-derived macrophages. Taken together our findings identify CD98 as a key mediator of both pro-fibrotic and acute inflammatory responses in the lung with relevance to AE- and chronic progression of IPF, and the priming of fibrotic lungs for acute inflammatory responses. They similarly implicate CD98 and galectin-3 as mediators of COVID pneumonitis and worse outcomes in ILD patients with COVID.
A human tubular aggregate myopathy mutation unmasks STIM1-independent rapid inactivation of Orai1 channels
Authors: Yeung Priscilla S.-W. , Yamashita Megumi , Prakriya Murali 
Published: August 2022

AbstractCa2+ release-activated Ca2+ (CRAC) channels are activated by direct physical interactions between Orai1, the channel protein, and STIM1, the endoplasmic reticulum Ca2+ sensor. A hallmark of CRAC channels is fast Ca2+-dependent inactivation (CDI) which provides negative feedback to limit Ca2+ entry through CRAC channels. Although STIM1 is thought to be essential for mediating CDI, the molecular mechanism of CDI remains largely unknown. Here, we examined a gain-of-function (GOF) human Orai1 disease mutation, L138F, that causes tubular aggregate myopathy (TAM). Through pairwise mutational analysis, we determine that large amino acid substitutions at either L138 or the neighboring T92 locus evoke highly Ca2+-selective currents in the absence of STIM1. We find that the GOF phenotype arises due to steric clash between L138 on TM2 and T92 located on the pore helix. Surprisingly, strongly activating L138 and T92 mutations also show CDI in the absence of STIM1, contradicting prevailing views that STIM1 is required for inactivation. CDI of constitutively open T92W and L138F mutants occurred with similar kinetics as WT Orai1 but showed enhanced intracellular Ca2+ sensitivity, which could be normalized by the addition of STIM1. Truncation of the Orai1 C-terminus reduced T92W CDI consistent with a key role for the Orai1 C-terminus for CDI. Overall, these results elucidate the molecular basis of the human TAM-linked mutation and indicate that CDI of CRAC channels is mediated by an Orai1-intrinsic mechanism with STIM1 tuning the calcium sensitivity of CDI.
DrosophilapVALIUM10 TRiP RNAi lines cause undesired silencing of Gateway-based transgenes
Authors: Stanković Dimitrije , Csordás Gábor , Uhlirova Mirka 
Published: August 2022

SUMMARYPost-transcriptional gene silencing using double-stranded RNA has revolutionized the field of functional genetics, allowing fast and easy disruption of gene function in various organisms. InDrosophila, many transgenic RNAi lines have been generated in large-scale efforts, including theDrosophilaTransgenic RNAi Project (TRiP), to facilitatein vivoknockdown of virtually anyDrosophilagene with spatial and temporal resolution. The available transgenic RNAi lines represent a fundamental resource for the fly community, providing an unprecedented opportunity to address a vast range of biological questions relevant to basic and biomedical research fields. However, caution should be applied regarding the efficiency and specificity of the RNAi approach. Here, we demonstrate that pVALIUM10-based RNAi lines, representing ~13% of the total TRiP collection (1,808 out of 13,410 TRiP pVALIUM-based RNAi lines), cause unintended off-target silencing of transgenes expressed from Gateway destination vectors generated via site-specific recombination. The silencing is mediated by targeting attB1 and attB2 sequences generated in the recombination reaction and included in the transcribed mRNA. Deleting these attB sites from the Gateway expression vector prevents silencing and restores expected transgene expression.
Attenuated foreign body response to subcutaneous implant in regenerative spiny mice (Acomys)
Authors: Gaire Janak , Dill Michele , Supper Valentina , Simmons Chelsey S. 
Published: August 2022

AbstractSpiny mice (Acomys) can regenerate after injury with minimal fibrosis. Whether Acomys retains the fibrosis-free feature in response to implanted devices is unknown, so we implanted polydimethylsiloxane (PDMS) subcutaneously in Acomys and Mus, a non-regenerative counterpart. In Acomys, we found reduced myeloid cell infiltration, fibroblast activation, and collagen deposition around the PDMS implant. These results suggest that Acomys can regulate FBR and may hold the key to improving implant lifetime and functionality.
Lipids Maintain Genomic Stability and Developmental Potency of Murine Pluripotent Stem Cells
Authors: Zhong Liangwen , Gordillo Miriam , Wang Xingyi , Qin Yiren , Huang Yuanyuan , Soshnev Alexey , Kumar Ritu , Nanjangud Gouri , James Daylon , Allis C. David , Evans Todd , Carey Bryce , Wen Duancheng 
Published: August 2022

ABSTRACTLipids play vital roles in cellular homeostasis and regulate pluripotency of human stem cells. However, the impact of lipids on murine pluripotent stem cells is unclear. While Mek1/2 and Gsk3β inhibition (“2i”) supports the maintenance of murine embryonic stem cells (ESCs) in a homogenous naïve state, prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impairs developmental potential. Additionally, 2i fails to support derivation and culture of fully potent female ESCs. Here we find that mouse ESCs cultured in 2i/LIF supplemented with lipid-rich albumin (AlbuMAX) undergo pluripotency transition yet maintain genomic stability and full potency over long-term culture. Mechanistically, lipids in AlbuMAX impact intracellular metabolism including nucleotide biosynthesis, lipid biogenesis, and TCA cycle intermediates, with enhanced expression of ZCAN4 and DNMT3s that prevent telomere shortening and DNA hypomethylation. In concert with 2i, lipids induce a formative-like pluripotent state through direct stimulation of Mek-mediated Erk2 phosphorylation, which also alleviates X chromosome loss in female ESCs. Importantly, both male and female “all-ESC” mice can be generated fromde novoderived ESCs using AlbuMAX-based media. Our findings underscore the importance of lipids to pluripotency and link nutrient cues to genome integrity in early development.
STAT3 signaling in B cells controls germinal center zone organization and recycling
Authors: Fike Adam J , Chodisetti Sathi Babu , Wright Nathaniel E , Bricker Kristen N , Domeier Phillip P , Maienschein-Cline Mark , Rosenfeld Aaron M , Luckenbill Sara A , Weber Julia L , Choi Nicholas M , Luning Prak Eline T , Mandal Malay , Clark Marcus R , Rahman Ziaur SM 
Published: August 2022

AbstractGerminal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we uncovered a B cell intrinsic role for STAT3 in GC DZ and LZ organization. Altered zonal organization of STAT3-deficient GCs dampened GC output of long-lived plasma cells (LL-PCs) but increased memory B cells (MBCs). Tfh-GC B cell interaction drive STAT3 tyrosine 705 and serine 727 phosphorylation in LZ B cells, facilitating their recycling into the DZ. An inducible system confirmed STAT3 is not involved in initiating or maintaining the GC but sustains GC zonal organization by regulating GC B cell recycling. RNAseq and ChIPseq analysis identified genes regulated by STAT3 that are critical for LZ cell recycling and transiting through the DZ proliferation and differentiation phases of the DZ. Thus, STAT3 signaling in B cells controls GC zone organization and recycling, and GC egress of LL-PCs, but negatively regulates MBC output.SummaryFike et al. describe a previously unrecognized mechanism by which B cell intrinsic STAT3 signaling controls the germinal center (GC) dark and light zone organization, GC B cell recycling, and GC output of long-lived plasma cells but negatively regulates memory B cells.
SIRT-1 is required for release of enveloped enteroviruses
Authors: Jassey Alagie , Logue James , Weston Stuart , Wagner Michael A. , Galitska Ganna , Miller Katelyn , Frieman Matthew B. , Jackson William T. 
Published: August 2022

ABSTRACTEnterovirus D68 is a re-emerging enterovirus that causes acute respiratory illness in infants and has recently been linked to Acute Flaccid Myelitis. Here, we show that the histone deacetylase, SIRT-1, is essential for autophagy and EV-D68 infection. Knockdown of SIRT-1 inhibits autophagy and reduces EV-D68 extracellular titers. The proviral activity of SIRT-1 does not require its deacetylase activity or functional autophagy. SIRT-1’s proviral activity is, we demonstrate, mediated through the repression of ER stress. Inducing ER stress through thapsigargin treatment or SERCA2A knockdown in SIRT-1 knockdown cells had no additional effect on EV-D68 extracellular titers. Knockdown of SIRT-1 also decreases poliovirus and SARS-CoV-2 titers but not coxsackievirus B3. In non-lytic conditions, EV-D68 is primarily released in an enveloped form, and SIRT-1 is required for this process. Our data show that SIRT-1, through its translocation to the cytosol, is critical to promote the release of enveloped EV-D68 viral particles.
CGIAR BARLEY BREEDING TOOLBOX: A diversity panel to facilitate breeding and genomic research in the Developing World
Authors: Bouhlal O. , Visioni A. , Verma R.P.S. , Kandil M. , Gyawali S. , Capettini F. , Sanchez-Garcia M. 
Published: August 2022

AbstractDespite the reduced cost of the new genotyping technologies, many public and private breeding programs, mostly in developing countries, still cannot afford them, hindering their research. The objective of the present study was to identify and assemble an Association Mapping panel of widely diverse barley genotypes to serve as a barley breeding toolbox, especially for the Developing World. The main criteria were: i) to be representative of the germplasm grown in the Developing World; ii) to cover a wide range of genetic variability and iii) to be of public domain. For it, we assembled and genotyped a Global Barley Panel (GBP) of 530 genotypes representing a wide range of row-types, end-uses, growth habits, geographical origins and environmental conditions. The GBP accessions were genotyped using the barley Infinium iSelect 50K chip. A total of 40,342 SNP markers were polymorphic and displayed an average polymorphism information content (PIC) of 0.35, with 66% of them exceeding PIC=0.25. The analysis of the population structure identified 8 sub-populations mostly linked to the geographical origin of the lines (Europe, Australia, USA, Canada, Africa, Latin-America, ICARDA and others), four of them of significant ICARDA origin. The 16 allele combinations at 4 major flowering genes (HvVRN-H3, HvPPD-H1, HvVRN-H1 and HvCEN) explained 11.07% genetic variation and were linked to the geographic origins of the lines studied. Among origins, ICARDA material (n= 257) showed wide diversity as revealed by the highest number of polymorphic loci (99.76% of all polymorphic SNPs in GBP), number of private alleles and Nei’s gene diversity and the fact that ICARDA lines were present in all 8 sub-populations and carried all 16 allelic combinations at phenology genes. Due to their genetic diversity and their representativity of the germplasm adapted to the Developing World, 312 ICARDA lines and cultivated landraces were pre-selected to form the CGIAR Barley Breeding Toolbox (CBBT). Using the genotypic data and the Mean of Transformed Kinships method, we assembled the CBBT, an Association Mapping panel of 250 accessions capturing most of the allelic diversity in the global panel. The CBBT preserves a good balance between row types as well as a good representation of both allelic combinations identified at most important phenological loci and sub-populations of the GBP. The CBBT lines together with their genotypic data will be made available to breeders and researchers worldwide to serve as a collaborative tool to underpin the genetic mechanisms of traits of interest for barley cultivation.