bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA-1273 Vaccine-elicited Neutralization of SARS-CoV-2 Omicron in Adolescents and Children
Authors: Girard Bethany , Tomassini Joanne E , Deng Weiping , Maglinao Maha , Zhou Honghong , Figueroa Amparo , Ghamloush Sabine Schnyder , Montefiori David C , Das Rituparna , Pajon Rolando 
Published: January 2022

AbstractBackgroundThe highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron variant is a global concern. This study assessed the neutralization activity of two-dose regimens of mRNA-1273 vaccination against Omicron in adults, adolescents and children.MethodsNeutralizing activity against the Omicron variant was evaluated in serum samples from adults (≥18 years) in the phase 3, Coronavirus Efficacy (COVE) and from adolescents (12-17 years) in the TeenCOVE trials following a two-dose regimen of 100 µg mRNA-1273 and from children (6-<12 years) in the KidCOVE trial administered two doses of 50 µg mRNA-1273. Neutralizing antibody geometric mean ID50 titers (GMT) were measured using a lentivirus-based pseudovirus neutralizing assay at day 1 and 4 weeks (day 57) following the second mRNA-1273 dose, compared with wild-type (D614G).ResultsAt 4 weeks following a second dose of mRNA-1273 (100 µg), the GMT was reduced 28.8-fold compared with D614G in adults (≥18 years). In adolescents (12-17 years), the GMT was 11.8-fold lower than D614G, 4 weeks after a second dose of mRNA-1273 (100 µg), and compared with adults, were 1.5- and 3.8-fold higher for D614G and the Omicron variant, respectively. In children (6-<12 years), 4 weeks post-second dose of 50 µg mRNA-1273, Omicron GMTs were reduced 22.1-fold versus D614G and were 2.0-fold higher for D614G and 2.5-fold higher for Omicron compared with adults.ConclusionsA two-dose regimen of 100 µg mRNA-1273 in adolescents and of 50 µg in children elicited neutralization responses against the Omicron variant that were reduced compared with the wild-type D614G, and numerically higher than those in adults.
The MU Study of Seropositivity and Risk for SARS-CoV-2 and COVID-19: Crucial Behavioral and Immunological Data from Midwestern College Students
Authors: Myroniuk Tyler W. , Hermsen Joan M. , Hamilton Christal , David Ifeolu , Teti Michelle , Ranjit Yerina S. , Woodrey Shannen N. , Stilley Julie A.W. , Teixeiro Emma , Guan Yue , Daniels Mark , Schatz Enid 
Published: January 2022

AbstractObjectiveWe describe our Fall 2020 study of college students’ COVID-19 related behaviors, attitudes, and antibody test results.ParticipantsThe study included 1,446 randomly selected and self-enrolled undergraduate and graduate students from a midwestern university.MethodsAn online survey was distributed to a sample of students, between September and December 2020. A sub-group also participated in a SARS-CoV-2 antibody blood draw.ResultsNearly half of students reported a prior COVID-19 test with 22% indicating a positive test, which represents an 11% positivity rate across all student participants. Of those who participated in antibody testing, 15.1% tested positive for SARS-CoV-2 antibodies. Seventy-seven percent of participants said they would get vaccinated. One-third of students reported moderate to severe generalized anxiety disorder and 13% reported moderate to severe depression.ConclusionsThis study informed campus decisions in Fall 2020. The importance of effective public health messaging on campus should continue in the future.
Childhood vaccination coverage by socioeconomic, geographic, maternal, child, and healthcare characteristics in Nigeria: equity impact analysis
Authors: Williams Sarah V , Akande Tanimola , Abbas Kaja 
Published: January 2022

AbstractBackgroundNigeria has a high proportion of the world’s underimmunised children. We estimated the inequities in childhood immunisation coverage associated with socioeconomic, geographic, maternal, child, and healthcare characteristics among children aged 12-23 months in Nigeria using a social determinants of health perspective.MethodsWe first conducted a systematic review focused on inequities in childhood immunisation in low- and middle-income countries to identify the social determinants of childhood immunisation. To identify inequities in basic vaccination coverage in Nigeria (1-dose BCG, 3-dose DTP-HepB-Hib (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B), 3-dose polio, and 1-dose measles) of 6,059 children aged 12-23 months using the 2018 Nigeria Demographic and Health Survey, we conducted multiple logistic regression to analyse the association of basic vaccination with these determinants.ResultsWe identified social determinants of immunisation: household wealth, religion, and ethnicity (socioeconomic characteristics); region and place of residence (geographic characteristics); maternal age at birth, maternal education, and maternal household head status (maternal characteristics); sex of child, and birth order (child characteristics); antenatal care and birth setting (healthcare characteristics). While basic vaccination coverage was 31% (95% CI: 29–33), 19% (95% CI:18–21) of children aged 12-23 months had received none of the basic vaccines. After controlling for background characteristics, there was a significant increase in the odds of basic vaccination by household wealth, antenatal care, delivery in a health facility, maternal age and maternal education. Children of Fulani ethnicity in comparison to children of Igbo ethnicity had lower odds of receiving basic vaccinations.ConclusionsChildren from the poorest households, of Fulani ethnicity, who were born in home settings, and with young mothers with no formal education nor antenatal care, were associated with lower odds of basic vaccination in Nigeria. Basic vaccination coverage is below target levels for all groups and we recommend a proportionate universalism approach for addressing the immunisation barriers.
Massive covidization of research citations and the citation elite
Authors: Ioannidis John P.A. , Bendavid Eran , Salholz-Hillel Maia , Boyack Kevin W. , Baas Jeroen 
Published: January 2022

ABSTRACTMassive scientific productivity accompanied the COVID-19 pandemic. We evaluated the citation impact of COVID-19 publications relative to all scientific work published in 2020-2021 and assessed the impact on scientist citation profiles. Using Scopus data until August 1, 2021, COVID-19 items accounted for 4% of papers published, 20% of citations received to papers published in 2020-2021 and >30% of citations received in 36 of the 174 disciplines of science (up to 79.3% in General and Internal Medicine). Across science, 98 of the 100 most-cited papers published in 2020-2021 were related to COVID-19. 110 scientists received >=10,000 citations for COVID-19 work, but none received >=10,000 citations for non-COVID-19 work published in 2020-2021. For many scientists, citations to their COVID-19 work already accounted for more than half of their total career citation count. Overall, these data show a strong covidization of research citations across science with major impact on shaping the citation elite.
Observing non-covalent interactions in experimental electron density for macromolecular systems: A novel perspective for protein–ligand interaction research
Authors: Ding Kang , Yin Shiqiu , Li Zhongwei , Jiang Shiju , Yang Yang , Zhou Wenbiao , Zhang Yingsheng , Huang Bo 
Published: January 2022

ABSTRACTWe report for the first time the use of experimental electron density (ED) in the Protein Data Bank for modeling non-covalent interactions (NCIs) for protein–ligand complexes. Our methodology is based on the reduced electron density gradient (RDG) theory describing intermolecular NCI by ED and its first derivative. We established a database called the Experimental NCI Database (ExptNCI;http://ncidatabase.stonewise.cn/#/nci) containing ED saddle points, indicating ~200,000 NCIs from over 12,000 protein–ligand complexes. We also demonstrated the use of the database for depicting amide–π interactions in a protein–ligand binding system. In summary, the database provides details on experimentally observed NCIs for protein–ligand complexes and can support future studies, including studies on rarely documented NCIs and the development of artificial intelligent models for protein–ligand binding prediction.
Close relatives of MERS-CoV in bats use ACE2 as their functional receptors
Authors: Xiong Qing , Cao Lei , Ma Chengbao , Liu Chen , Si Junyu , Liu Peng , Gu Mengxue , Wang Chunli , Shi Lulu , Tong Fei , Huang Meiling , Li Jing , Zhao Chufeng , Shen Chao , Chen Yu , Zhao Huabin , Lan Ke , Wang Xiangxi , Yan Huan 
Published: January 2022

SummaryMiddle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors1–4. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic5. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes’ S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using “MERS-CoV-2” with both high fatality and transmission rate.
Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype
Authors: O’Shea T.M. , Ao Y. , Wang S. , Wollenberg A.L. , Kim J.H. , Ramos Espinoza R.A. , Czechanski A. , Reinholdt L.G , Deming T.J. , Sofroniew M.V. 
Published: January 2022

AbstractNeural progenitor cells (NPC) represent potential cell transplantation therapies for CNS injuries. To understand how lesion environments influence transplanted NPC fate in vivo, we derived NPC expressing a ribosomal protein-hemagglutinin tag (RiboTag) for transcriptional profiling of transplanted NPC. Here, we show that NPC grafted into uninjured CNS generate cells that are transcriptionally similar to healthy astrocytes and oligodendrocyte lineages. In striking contrast, NPC transplanted into serum-exposed CNS lesions after stroke or spinal cord injury generate cells that share transcriptional, morphological and functional features with newly proliferated host astroglia that restrict inflammation and fibrosis and thereby protect adjacent neural tissue. Our findings reveal overlapping differentiation potentials of grafted NPC and proliferating host astrocytes; and show that in the absence of other interventions, non-cell autonomous cues in CNS lesions direct the differentiation of grafted NPC predominantly towards a naturally occurring neuroprotective wound repair astroglial phenotype.
Cytotoxic T lymphocytes targeting a conserved SARS-CoV-2 spike epitope are efficient serial killers
Authors: Fathi Mohsen , Charley Lindsey , Cooper Laurence J.N. , Varadarajan Navin , Meyer Daniel 
Published: January 2022

AbstractUnderstanding the cellular immune response to infections, cancers and vaccines lags behind the investigation of humoral responses. While neutralizing antibody responses wane over time, the ability of T cells to recognize viruses including SARS-CoV-2 is instrumental to providing long-term immunity. Although T-cell receptor (TCR) repertoire screening can provide insights into the skewing of a T-cell response elicited upon vaccination or infection, they unfortunately provide no assessment into the functional capacity of T cells or their ability to eliminate virally infected targets. We have used time-lapse imaging microscopy in nanowell grids (TIMING) to integrate the migration of individual T cells with analysis of effector functions including cytokine secretion and cytotoxicity. Machine learning is then applied to study thousands of videos of dynamic interactions as T cells with specificity for SARS-CoV-2 eliminate targets bearing spike protein as a surrogate for viral infection. Our data provide the first direct evidence that cytotoxic T lymphocytes from a convalescent patient targeting an epitope conserved across all known variants of concern (VoC) are serial killers capable of eliminating multiple infected targets. These data have implications for development of vaccines to provide broad and sustained cellular immunity and for the recovery and monitoring of individuals who have been exposed to SARS-CoV-2.Multidisciplinary abstractWe present an imaging platform that uses artificial intelligence (AI) to track thousands of individual cell-cell interactions within nanowell arrays. We apply this platform to quantify how the T cell component of adaptive immunity responds to infections. Our results show that T cells specific for a conserved epitope within the SARS-CoV-2 spike protein are serial killers that can rapidly eliminate virally infected targets. The ability to map the functional capacity of T cells and their ability to kill infected cells provides fundamental insights into the immunology of vaccines and recovery from infections.Graphical Abstract
Biomolecular Tau condensation is linked to Tau accumulation at the nuclear envelope
Authors: Hochmair Janine , Exner Christian , Franck Maximilian , Dominguez-Baquero Alvaro , Diez Lisa , Brognaro Hévila , Kraushar Matthew , Mielke Thorsten , Radbruch Helena , Kaniyappan Senthil , Falke Sven , Mandelkow Eckhard , Betzel Christian , Wegmann Susanne 
Published: January 2022

AbstractBiomolecular condensation of the neuronal microtubule-associated protein Tau (MAPT) can be induced by coacervation with polyanions like RNA, or by molecular crowding. Tau condensates have been linked to both functional microtubule binding and pathological aggregation in neurodegenerative diseases. We find that molecular crowding and coacervation with RNA, likely coexisting in the cytosol, synergize to enable Tau condensation at physiological buffer conditions and produce condensates with a strong affinity to charged surfaces. During condensate-mediated microtubule polymerization, this synergy enhances bundling and spatially arranges microtubules. We further show that different Tau condensates efficiently induce pathological Tau in cells, including small accumulations at the nuclear envelope that correlate with nucleocytoplasmic transport deficits. Fluorescent lifetime imaging reveals different molecular packing densities of Tau in cellular accumulations, and a condensate-like density for nuclear envelope Tau. These findings suggest that a complex interplay between interaction partners, post-translational modifications, and molecular crowding regulates the formation and function of Tau condensates. Conditions leading to prolonged existence of Tau condensates may induce the formation of seeding-competent Tau and lead to distinct cellular Tau accumulations.
Songbird parents coordinate offspring provisioning at fine spatio-temporal scales
Authors: Baldan Davide , Van Loon E. Emiel 
Published: January 2022

AbstractFor parents, rearing offspring together is far from a purely cooperative exercise, as a conflict of interest (‘sexual conflict’) exists over their optimum level of care. Recent theory emphasises that sexual conflict can be evolutionarily resolved, and complete parental cooperation can occur if parents directly respond (‘negotiate’) to each other and coordinate their level of care. Despite numerous experiments show that parents are responsive to each other, we still lack empirical evidence of the behavioural mechanisms by which this negotiation occurs. In this study, we investigated the spatio-temporal coordination of parental provisioning behaviour as a possible mechanism of negotiation over parental care. We deployed an automated radio-tracking technology to track the provisioning activity of wild great tit (Parus major) pairs during chick rearing. Our analyses represent the first detailed spatial and temporal description of foraging coordination in songbird parents in a natural context. We demonstrate that the foraging behaviour of the two parents is highly coordinated in space and time, with parents changing their foraging locations in conjunction with their partners’ movements. Therefore, foraging coordination could be a mechanism by which parents directly monitor and respond to each other’s level of investment.
HNRNPK is retained in the cytoplasm by Keratin 19 to stabilize target mRNAs
Authors: Fallatah Arwa , Anastasakis Dimitrios G. , Manzourolajdad Amirhossein , Sharma Pooja , Wang Xiantao , Jacob Alexis , Alsharif Sarah , Elgerbi Ahmed , Coulombe Pierre A. , Hafner Markus , Chung Byung Min 
Published: January 2022

AbstractHeterogeneous nuclear ribonucleoprotein K (HNRNPK) regulates pre-mRNA processing and long non-coding RNA localization in the nucleus. It was previously shown that shuttling of HNRNPK to the cytoplasm promotes cell proliferation and cancer metastasis. However, the mechanism of HNRNPK cytoplasmic localization, its cytoplasmic RNA ligands, and impact on posttranscriptional gene regulation remain uncharacterized. Here we show that the intermediate filament protein Keratin 19 (K19) directly interacts with HNRNPK and sequesters it in the cytoplasm. Correspondingly, in K19 knockout breast cancer cells, HNRNPK does not localize in the cytoplasm, resulting in reduced cell proliferation. We mapped cytoplasmic HNRNPK target mRNAs using PAR-CLIP where transcriptome data to show that, in the cytoplasm, HNRNPK stabilizes target mRNAs bound to the 3’ untranslated region at the expected C-rich sequence elements. Furthermore, these mRNAs are typically involved in cancer progression and include the p53 signaling pathway that is dysregulated upon HNRNPK knockdown or K19 knockout. This study identifies how a cytoskeletal protein can directly regulate gene expression by controlling subcellular localization of RNA binding proteins to support pathways involved in cancer progression.
CGRP Administration into the Cerebellum Evokes Migraine-like Behaviors Predominately in Female Mice
Authors: Wang Mengya , Duong Thomas L. , Rea Brandon J. , Waite Jayme S. , Huebner Michael W. , Flinn Harold C. , Russo Andrew F. , Sowers Levi P. 
Published: January 2022

AbstractThe neuropeptide calcitonin gene-related peptide (CGRP) is a major player in migraine pathophysiology. Previous preclinical studies demonstrated that intracerebroventricular administration of CGRP caused migraine-like behaviors in mice, but the sites of action in the brain remain unidentified. The cerebellum has the most CGRP binding sites in the central nervous system and is increasingly recognized as both a sensory and motor integration center. The objective of this study was to test whether the cerebellum, particularly the medial cerebellar nuclei (MN), might be a site of CGRP action. In this study, CGRP was directly injected into the right MN of C57BL/6J mice via a cannula. A battery of behavioral tests was done to assess migraine-like behaviors. CGRP caused light aversion measured as decreased time in the light zone even with dim light. The mice also spent more time resting in the dark zone, but not the light, along with decreased rearing and transitions between zones. These behaviors were similar for both sexes. In contrast, significant responses to CGRP were seen only with female mice in the open field assay, von Frey test, and automated squint assay, indicating anxiety, tactile hypersensitivity, and spontaneous pain, respectively. In male mice, the responses had the same trend as females but did not reach statistical significance. No detectable effect of CGRP on gait was observed in either sex. These results suggest that CGRP in the MN causes light aversion in males, while in females, light aversion is accompanied by increased anxiety, tactile hypersensitivity, and spontaneous pain. A caveat is that we cannot exclude contributions from other cerebellar regions in addition to the MN due to diffusion of the injected peptide. These results reveal the cerebellum as a new site of CGRP actions that may contribute to migraine pathophysiology and possibly its prevalence in females.
Repressing ABCB7 Potentiates Cisplatin Response in Pediatric Group 3 Medulloblastoma by Triggering Ferroptosis
Authors: Kanchan Ranjana K. , Perumal Naveenkumar , Khan Parvez , Doss David , Gopalakrishnan Prakadeeshwari , Venkata Ramakanth Chirravuri , Thapa Ishwor , Vengoji Raghupathy , Kaushal Jyoti B. , Siddiqui Jawed A. , Nasser Mohd Wasim , Batra Surinder K. , Mahapatra Sidharth 
Published: January 2022

AbstractMedulloblastomas (MB) are the most common malignant pediatric brain tumor and a leading cause of childhood mortality. Aggressive tumors belonging to group 3 (G3MB) are distinguished by a marked reduction in programmed cell death by ferroptosis. These aggressive tumors also enrich iron transport and glutathione metabolism. A highly enriched pathway in these tumors is iron-sulfur (Fe-S) cluster binding corresponding to significant upregulation of ABCB7, a poor prognostic feature linked with accelerated mortality. This study elucidated whether repressing ABCB7 activates ferroptosis to mitigate G3MB aggressiveness and whether this pathway is pharmacologically targetable.In silicoandin vitroanalyses confirmed upregulation of ABCB7 and GPX4, the central regulator of ferroptosis, in G3MB cell lines and tumors. Repressing ABCB7 (miR-1253OE, siABCB7, sh-ABCB7) induced iron overload, elicited oxidative stress, and triggered lipid peroxidation, leading to an abrogation of medullosphere formation and cell death by ferroptosis. Intriguingly, fractionation studies revealed that ABCB7 repression abrogated GPX4 expression, most likely by GSH depletion. Repressing ABCB7 induced mitochondrial dysfunction and reduced oxidative phosphorylation. Cisplatin, a chemotherapeutic mainstay of G3MB, induces cell death by DNA crosslinking. In ABCB7 repressed cell lines, the IC50of cisplatin was halved, resulting in augmented oxidative stress and lipid peroxidation, culminating in a higher index of ferroptosis. Artesunate, an anti-malarial drug capable of triggering ferroptosis, was shown to synergize with cisplatin, reducing tumor burden and significantly prolonging survival. Taken together, the current study illustrates how targeting iron transport can augment ferroptosis in G3MBs. It further identifies an FDA-approved drug capable of recapitulating these effects and potentiating mainstay chemotherapy.