bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting developmental relationships of tumor resident and circulating T cells in ovarian cancer
Authors: Carneiro Mayra S. , Bareche Yacine , Zhao Cheng , Thébault Pamela , Rahimi Kurosh , Provencher Diane , Samouélian Vanessa , Cormier Béatrice , Cailhier Jean-François , Mes-Masson Anne-Marie , Petropoulos Sophie , Stagg John , Lapointe Réjean 
Published: March 2023

ABSTRACTCharacterizing T cell populations and understanding their developmental relationships may help design more effective cancer immunotherapies. We coupled single-cell transcriptomics and T cell receptor (TCR) αβ profiling of intratumoral and peripheral T cells in ovarian cancer patients to identify transcriptional programs and infer their relationship by trajectory and TCR overlap analyses. We proposed a model of differentiation pathway from an intermediate GZMH-expressing CD8 T cell subset found in the blood and tumor that progressively reinforces the exhaustion and tissue residency programs from aCCL4-expressing cluster towardsXCL1- andCXCL13-expressing terminally exhausted cells. Inferred cell communication analysis suggests that interaction withCXCL13-expressing CD4 T cells, which we refer to as Tfh-like cells, sustains the effector function of this intermediate GZMH-expressing CD8 T cell subset. Moreover, our results suggest that Tfh-like cells attract cells expressingGPR183through the production of its ligand 7α,25 dihydroxycholesterol (7α,25-HC). Finally, we demonstrated thatGPR183is highly expressed in a subset of pre-effectorGZMK-expressing CD8 T cells and plasmacytoid dendritic cells. Collectively, our results suggest that Tfh-like cells expressing IL-21 help promote antitumor immunity against ovarian tumors by coordinating the action of immune cells responsive to 7α,25-HC.
Mapping global marine biodiversity under sparse data conditions
Authors: Righetti Damiano , Vogt Meike , Gruber Nicolas , Zimmermann Niklaus E. 
Published: March 2023

AbstractSparse and spatiotemporally highly uneven sampling efforts pose major challenges to obtaining accurate species and biodiversity distributions. Here, we demonstrate how limited surveys can be integrated with global models to uncover hotspots and distributions of marine biodiversity. We test the skill of recent and advanced species distribution model setups to predict the global biodiversity of >560 phytoplankton species from 183,000 samples. Recent setups attain quasi-null skill, while models optimized for sparse data explain up to 91% of directly observed species richness variations. Using a refined spatial cross-validation approach to address data sparsity at multiple temporal resolutions we find that background choices are the most critical step. Predictor variables selected from broad sets of drivers and tuned for each species individually improve the models’ ability in identifying richness hotspots and latitude gradients. Optimal setups identify tropical hotspots, while common ones lead to polar hotspots disjunct from general marine diversity. Our results show that unless great care is taken to validate models, conservation areas in the ocean may be misplaced. Yet a game-changing advance in mapping diversity can be achieved by addressing data-sparse conditions that prevail for >80% of extant marine species.Authorship statementAll authors designed the research and contributed to the writing. D.R. designed the multiscale validation and predictor selection methods, developed the figures with input by M.V. and N.E.Z., performed research, and wrote the first draft.
Brain Organoid Computing for Artificial Intelligence
Authors: Cai Hongwei , Ao Zheng , Tian Chunhui , Wu Zhuhao , Liu Hongcheng , Tchieu Jason , Gu Mingxia , Mackie Ken , Guo Feng 
Published: March 2023

AbstractBrain-inspired hardware emulates the structure and working principles of a biological brain and may address the hardware bottleneck for fast-growing artificial intelligence (AI). Current brain-inspired silicon chips are promising but still limit their power to fully mimic brain function for AI computing. Here, we developBrainoware, living AI hardware that harnesses the computation power of 3D biological neural networks in a brain organoid. Brain-like 3Din vitrocultures compute by receiving and sending information via a multielectrode array. Applying spatiotemporal electrical stimulation, this approach not only exhibits nonlinear dynamics and fading memory properties but also learns from training data. Further experiments demonstrate real-world applications in solving non-linear equations. This approach may provide new insights into AI hardware.
Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes
Authors: Nagy Nadine , Kaber Gernot , Sunkari Vivekananda G. , Marshall Payton L. , Hargil Aviv , Kuipers Hedwich F. , Ishak Heather D. , Bogdani Marika , Hull Rebecca L. , Grandoch Maria , Fischer Jens W. , McLaughlin Tracey L. , Wight Thomas N. , Bollyky Paul L. 
Published: March 2023

ABSTRACTPancreatic β-cell dysfunction and death are central to the pathogenesis of type 2 diabetes (T2D). We have identified a novel role for the inflammatory extracellular matrix polymer hyaluronan (HA) in this pathophysiology. Low levels of HA are present in healthy pancreatic islets. However, HA substantially accumulates in cadaveric islets of human T2D and islets of the db/db mouse model of T2D in response to hyperglycemia. Treatment with 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, or the deletion of the major HA receptor CD44, preserve glycemic control and insulin levels in db/db mice despite ongoing weight gain, indicating a critical role for this pathway in T2D pathogenesis. 4-MU treatment and the deletion of CD44 likewise preserve glycemic control in other settings of β-cell injury including streptozotocin treatment and islet transplantation. Mechanistically, we find that 4-MU increases the expression of the apoptosis inhibitor survivin, a downstream transcriptional target of CD44 dependent on HA/CD44 signaling, on β-cells such that caspase 3 activation does not result in β-cell apoptosis. These data indicate a role for HA accumulation in diabetes pathogenesis and suggest that it may be a viable target to ameliorate β-cell loss in T2D. These data are particularly exciting, because 4-MU is already an approved drug (also known as hymecromone), which could accelerate translation of these findings to clinical studies.
An intact amber-free HIV-1 system for in-virus protein bioorthogonal click labeling that delineates envelope conformational dynamics
Authors: Ao Yuanyun , Grover Jonathan R. , Han Yang , Zhong Guohua , Qin Wenyi , Ghimire Dibya , Haque Anzarul , Bhattacharjee Rajanya , Zhang Baoshan , Arthos James , Lemke Edward A. , Kwong Peter D. , Lu Maolin 
Published: March 2023

AbstractThe HIV-1 envelope (Env) glycoprotein is conformationally dynamic and mediates membrane fusion required for cell entry. Single-molecule fluorescence resonance energy transfer (smFRET) of Env using peptide tags has provided mechanistic insights into the dynamics of Env conformations. Nevertheless, using peptide tags risks potential effects on structural integrity. Here, we aim to establish minimally invasive smFRET systems of Env on the virus by combining genetic code expansion and bioorthogonal click chemistry. Amber stop-codon suppression allows site-specifically incorporating noncanonical/unnatural amino acids (ncAAs) at introduced amber sites into proteins. However, ncAA incorporation into Env (or other HIV-1 proteins) in the virus context has been challenging due to low copies of Env on virions and incomplete amber suppression in mammalian cells. Here, we developed an intact amber-free virus system that overcomes impediments from preexisting ambers in HIV-1. Using this system, we successfully incorporated dual ncAAs at amber-introduced sites into Env on intact virions. Dual-ncAA incorporated Env retained similar neutralization sensitivities to neutralizing antibodies as wildtype. smFRET of click-labeled Env on intact amber-free virions recapitulated conformational profiles of Env. The amber-free HIV-1 infectious system also permits in-virus protein bioorthogonal labeling, compatible with various advanced microscopic studies of virus entry, trafficking, and egress in living cells.Amber-free HIV-1 infectious systems actualized minimal invasive Env tagging for smFRET, versatile for in-virus bioorthogonal click labeling in advanced microscopic studies of virus-host interactions.
ClockBase: a comprehensive platform for biological age profiling in human and mouse
Authors: Ying Kejun , Tyshkovskiy Alexander , Trapp Alexandre , Liu Hanna , Moqri Mahdi , Kerepesi Csaba , Gladyshev Vadim N. 
Published: March 2023

ABSTRACTAging represents the greatest risk factor for chronic diseases and mortality, but to understand it we need the ability to measure biological age. In recent years, many machine learning algorithms based on omics data, termed aging clocks, have been developed that can accurately predict the age of biological samples. However, there is currently no resource for systematic profiling of biological age. Here, we describeClockBase, a platform that features biological age estimates based on multiple aging clock models applied to more than 2,000 DNA methylation datasets and nearly 200,000 samples. We further provide an online interface for statistical analyses and visualization of the data. To show how this resource could facilitate the discovery of biological age-modifying factors, we describe a novel anti-aging drug candidate, zebularine, which reduces the biological age estimates based on all aging clock models tested. We also show that pulmonary fibrosis accelerates epigenetic age. Together,ClockBaseprovides a resource for the scientific community to quantify and explore biological ages of samples, thus facilitating discovery of new longevity interventions and age-accelerating conditions.
COVID-19 adenoviral vector vaccination elicits a robust memory B cell response with the capacity to recognize Omicron BA.2 and BA.5 variants
Authors: Fryer Holly A. , Hartley Gemma E. , Edwards Emily S.J. , Varese Nirupama , Boo Irene , Bornheimer Scott J. , Hogarth P. Mark , Drummer Heidi E. , O’Hehir Robyn E. , van Zelm Menno C. 
Published: March 2023

AbstractFollowing the COVID-19 pandemic caused by SARS-CoV-2, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe disease may be mediated by immune memory cells. We here evaluated plasma antibody and memory B cells (Bmem) targeting the Spike receptor binding domain (RBD) elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, and compared this to the response elicited by the mRNA vaccine BNT162b2 (Pfizer-BioNTech). Whole blood was sampled from 31 healthy adults pre-vaccination, and four weeks after dose one and dose two of ChAdOx1. Neutralizing antibodies (NAb) against SARS-CoV-2 were quantified at each timepoint. Recombinant RBDs of the Wuhan-Hu-1 (WH1), Delta, BA.2, and BA.5 variants were produced for ELISA-based quantification of plasma IgG and incorporated separately into fluorescent tetramers for flow cytometric identification of RBD-specific Bmem. NAb and RBD-specific IgG levels were over eight times lower following ChAdOx1 vaccination than BNT162b2. In ChAdOx1-vaccinated individuals, median plasma IgG recognition of BA.2 and BA.5 as a proportion of WH1-specific IgG was 26% and 17%, respectively. All donors generated resting RBD-specific Bmem, which were boosted after the second dose of ChAdOx1, and were similar in number to those produced by BNT162b2. The second dose of ChAdOx1 boosted Bmem that recognized VoC, and 37% and 39% of WH1-specific Bmem recognized BA.2 and BA.5, respectively. These data uncover mechanisms by which ChAdOx1 elicits immune memory to confer effective protection against severe COVID-19.
OsNLP4-OsD3 module integrates nitrogen-iron nutrient signals to promote rice tillering by repressing strigolactone signaling
Authors: Song Ying , Wan Guang-Yu , Wang Jing-Xian , Yu Lin-Hui , Wu Jie , Xiang Cheng-Bin 
Published: March 2023

AbstractRice tillers are a major yield component regulated by phytohormones and nutrients. How nutrients interact with phytohormones to control tillering remains largely elusive. Here, we report a novel mechanism by which the transcription factor NIN-like protein 4 (OsNLP4) integrates nitrogen (N)-iron (Fe) nutrient signals to promote tillering by repressingOsD3in strigolactone (SL) signaling. We show that the N-Fe balance modulates OsNLP4 nuclear accumulation, which is increased by Fe through H2O2reduction. Furthermore, OsNLP4 upregulates multiple H2O2scavenging genes, providing a positive regulatory loop for OsNLP4 nuclear accumulation. Our findings uncover a fundamental mechanism by which the OsNLP4-OsD3 module integrates N-Fe nutrient signals to downregulate SL signaling and thereby promote rice tillering and yield, thus facilitating sustainable agriculture worldwide.
Type I interferon signaling induces a delayed antiproliferative response in Calu-3 cells during SARS-CoV-2 infection
Authors: Cunha Juliana Bragazzi , Leix Kyle , Sherman Emily J. , Mirabelli Carmen , Kennedy Andrew A. , Lauring Adam S. , Tai Andrew W. , Wobus Christiane E. , Emmer Brian T. 
Published: March 2023

ABSTRACTDisease progression during SARS-CoV-2 infection is tightly linked to the fate of lung epithelial cells, with severe cases of COVID-19 characterized by direct injury of the alveolar epithelium and an impairment in its regeneration from progenitor cells. The molecular pathways that govern respiratory epithelial cell death and proliferation during SARS-CoV-2 infection, however, remain poorly understood. We now report a high-throughput CRISPR screen for host genetic modifiers of the survival and proliferation of SARS-CoV-2-infected Calu-3 respiratory epithelial cells. The top 4 genes identified in our screen encode components of the same type I interferon signaling complex –IFNAR1,IFNAR2,JAK1, andTYK2. The 5thgene,ACE2, was an expected control encoding the SARS-CoV-2 viral receptor. Surprisingly, despite the antiviral properties of IFN-I signaling, its disruption in our screen was associated with an increase in Calu-3 cell fitness. We validated this effect and found that IFN-I signaling did not sensitize SARS-CoV-2-infected cultures to cell death but rather inhibited the proliferation of surviving cells after the early peak of viral replication and cytopathic effect. We also found that IFN-I signaling alone, in the absence of viral infection, was sufficient to induce this delayed antiproliferative response. Together, these findings highlight a cell autonomous antiproliferative response by respiratory epithelial cells to persistent IFN-I signaling during SARS-CoV-2 infection. This response may contribute to the deficient alveolar regeneration that has been associated with COVID-19 lung injury and represents a promising area for host-targeted therapeutic development.
Reconstruction of the molecular evolution of Usutu virus in Germany: Insights into virus emersion and circulation
Authors: Bergmann Felicitas , Holicki Cora M. , Michel Friederike , Bock Sabine , Scuda Nelly , Priemer Grit , Kenklies Susanne , Siempelkamp Timo , Skuballa Jasmin , Sauerwald Claudia , Herms Louise , Muluneh Aemero , Peters Martin , Hlinak Andreas , Groschup Martin H. , Sadeghi Balal , Ziegler Ute 
Published: March 2023

AbstractUsutu virus (USUV) is a mosquito-borne flavivirus that is widely distributed in southern and central Europe. The zoonotic virus circulates primarily between birds and mosquitoes, can, however, in rare cases infect other mammals including humans. In the past USUV has been associated with mass mortalities in birds, formerly blackbirds and owls. Birds commonly succumb either due to the peracute nature of the infection or due to severe encephalitis. In Germany, USUV has spread rapidly since its first detection in 2010 in mosquitoes under the presence of susceptible host and vector species.Nonetheless, there is to date limited access to whole genome sequences resulting in the absence of in-depth phylogenetic and phylodynamic analyses. In this study, 118 wild and captive birds were screened using a nanopore sequencing platform with prior target enrichment via amplicons. Due to the high abundancy of Europe 3 and Africa 3 in Germany an ample quantity of associated whole genome sequences was generated and the most recent common ancestor could be determined for each lineage. The corresponding clock phylogeny revealed an introduction of USUV Europe 3 and Africa 3 into Germany three years prior to their first isolation in the avifauna in 2011 and 2014, respectively. Based on the clustering and temporal history of the lineages, evidence exists for the genetic evolution of USUV within Germany as well as new introductions thereof into the country.
“Ferric carboxymaltose has a higher distribution into myocardium than gadobutrol – a quantitative T1 mapping study in healthy volunteers”
Authors: Abdula Goran , Lundin Magnus , Nickander Jannike , Sörensson Peder , Sigfridsson Andreas , Themudo Raquel , Ugander Martin 
Published: March 2023

AbstractBackgroundThe dynamic tissue distribution of the clinically available intravenous iron substitution agent ferric carboxymaltose (FCM) is largely unknown. Notably, T1 mapping cardiovascular magnetic resonance (CMR) is highly sensitive for detecting myocardial iron.PurposeTo evaluate and quantify the dynamic tissue distribution of FCM using CMR.Materials and methodsT1 mapping was prospectively performed to determine T1 and the partition coefficient (lambda) in myocardium, liver, spleen and skeletal muscle up to 60 minutes after onset of a 15-minute-long infusion of 20 ml (50 mg iron/ml) FCM in healthy male volunteers. For comparison, myocardial lambda for gadobutrol (0.2 mmol/kg) was measured in a separate group of age-matched healthy male volunteers. The t-test was used for group comparisons.ResultsA total of 25 healthy male participants (mean±SD age 27±3 years) were evaluated. Subjects underwent CMR with intravenous FCM (n=8) or gadobutrol (n=17, age matched). T1 values of myocardium, blood, liver, spleen and skeletal muscle were all shortened after intravenous injection of FCM (p<0.001 for all). Lambda for FCM in myocardium and spleen remained constant over time after injection of FCM (mean±SEM 64±8% and 81±20%, respectively, 30 minutes after injection start), while lambda for FCM in liver and skeletal muscle increased over time. Myocardial lambda for FCM was higher than myocardial lambda for gadobutrol (64±8 vs 45±1%, p=0.003).ConclusionsT1 mapping can detect and quantify the dynamic tissue distribution of iron from ferric carboxymaltose in the myocardium, liver, spleen and skeletal muscle. Lambda in healthy myocardium for ferric carboxymaltose was markedly higher than lambda for gadobutrol, indicating that ferric carboxymaltose distributes to a greater extent into the myocardium than extracellular contrast agents, most likely due to additional distribution into the intracellular space.
Cerebrospinal fluid 2-hydroxyglutarate (2-HG) as a monitoring biomarker for IDH-mutant gliomas
Authors: Riviere-Cazaux Cecile , Lacey Jean M. , Carlstrom Lucas P. , Laxen William J. , Munoz-Casabella Amanda , Hoplin Matthew D. , Ikram Samar , Zubair Abdullah Bin , Andersen Katherine M. , Warrington Arthur E. , Decker Paul A. , Kaufmann Timothy J. , Campian Jian L. , Eckel-Passow Jeanette E. , Kizilbash Sani H. , Tortorelli Silvia , Burns Terry C. 
Published: March 2023

AbstractD-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas1,2, no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples from consenting patients during their disease course via intra-operative collection and Ommaya reservoirs. D-2-HG and D/L-2-HG consistently decreased following tumor resection and throughout chemoradiation in patients monitored longitudinally. Our early experience with this strategy demonstrates the potential for intracranial CSF D-2-HG as a monitoring biomarker for IDH-mutant gliomas.
Proteins and transcriptional dysregulation of the brain extracellular matrix in Parkinson’s disease: A systematic review
Authors: Rike Wote , Stern Shani 
Published: March 2023

AbstractThe extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural, organizational and functional changes in these macromolecules due to genetic variation or environmental stressors are thought to affect the cellular functions, and may result in disease. Most mechanistic studies to date usually focus on the cellular aspects of diseases and pay less attention to the relevance of the processes governing the dynamic nature of the extracellular matrix on disease pathogenesis. Here in this review, we gathered postmortem brain tissue and induced pluripotent stem cell (iPSC)-related studies from PubMed and Google scholar to identify, summarize and describe common macromolecular alterations in the expression of brain ECM components in Parkinson’s disease (PD). According to proteomic studies, proteins such as collagens, fibronectin, annexins and tenascins were recognized to be differentially expressed in Parkinson’s disease. Transcriptomic studies displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, and cell adhesion molecules in Parkinson’s disease. Limited number of relevant studies were accessed from our search indicating that much work still remains to be done to better understand the roles of the ECM in neurodegeneration and Parkinson’s disease. However, we believe that our review will elicit focused primary studies and thus, support the ongoing efforts of the discovery and development of diagnostic biomarkers as well as therapeutic agents for Parkinson’s disease.