bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner
Authors: Keeton Roanne , Richardson Simone I. , Moyo-Gwete Thandeka , Hermanus Tandile , Tincho Marius B. , Benede Ntombi , Manamela Nelia P. , Baguma Richard , Makhado Zanele , Ngomti Amkele , Motlou Thopisang , Mennen Mathilda , Chinhoyi Lionel , Skelem Sango , Maboreke Hazel , Doolabh Deelan , Iranzadeh Arash , Otter Ashley D. , Brooks Tim , Noursadeghi Mahdad , Moon James , Grifoni Alba , Weiskopf Daniela , Sette Alessandro , Blackburn Jonathan , Hsiao Nei-Yuan , Williamson Carolyn , Riou Catherine , Goga Ameena , Garrett Nigel , Bekker Linda-Gail , Gray Glenda , Ntusi Ntobeko A. B. , Moore Penny L. , Burgers Wendy A. 
Published: July 2021

SummaryThe Johnson and Johnson Ad26.COV2.S single dose vaccine represents an attractive option for COVID-19 vaccination in resource limited countries. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naïve with those either infected with the ancestral D614G virus, or infected in the second wave when Beta predominated. Prior infection significantly boosted spike binding antibodies, antibody-dependent cellular cytotoxicity and neutralizing antibodies against D614G, Beta and Delta, however neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses were induced after vaccination, regardless of prior infection. T cell recognition of variants was largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination following infection may result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.
Metabolomics and microbiome reveal impacts of rhizosphere metabolites on alfalfa continuous cropping
Authors: Wang Ruiting , Liu Jinxin , Jiang Wanyi , Ji Pingsheng , Li Yonggang 
Published: July 2021

AbstractAlfalfa long-term continuous cropping (CC) can pose a serious threat to alfalfa production. However, the mechanism of alfalfa CC obstacle is unclear as of today. In this study, we determined physic-chemical property, microbial population structure, and metabolite differences of alfalfa rhizosphere soils with CC for 1, 7, and 14-years based on analysis of metabolomics and microbiomics. Shifts of functional microorganisms in rhizosphere soil were analyzed, key metabolites and their effects on alfalfa seeds, seedlings and root rot pathogens were assessed. Based on anlysis, p-coumaric acid and ferulic acid on alfalfa seed and seedling growth and root rot pathogens were basically consistent with the influence of CC obstacles in the field. With the increase of CC years, the microbial community in soils changed from fungal to bacterial, and beneficial microorganisms decreased with the increase of CC years, which echoed the performance of alfalfa CC obstacles. The autotoxicity of p-coumaric acid was the strongest.This study fully proved that the continuous accumulation of autotoxic substances in alfalfa rhizosphere was the key factor causing alfalfa CC obstacles.
Cash versus Lotteries: COVID-19 Vaccine Incentives Experiment*
Authors: Duch Raymond M. , Barnett Adrian , Filipek Maciej , Roope Laurence , Violato Mara , Clarke Philip 
Published: July 2021

AbstractGovernments are considering financial incentives to increase vaccine uptake to end the COVID-19 pandemic. Incentives being offered include cash-equivalents such as vouchers or being entered into lotteries. Our experiment involved random assignment of 1,628 unvaccinated participants in the United States to one of three 45 second informational videos promoting vaccination with messages about: (a) health benefits of COVID-19 vaccines (control); (b) being entered into lotteries; or (c) receiving cash equivalent vouchers. After seeing the control health information video, 16% of individuals wanted information on where to get vaccinated. This compared with 14% of those assigned to the lottery video (odds ratio of 0.82 relative to control: 95% credible interval 0.57-1.17) and 22% of those assigned to the cash voucher video (odds ratio of 1.53 relative to control: 95% credible interval 1.11-2.11). These results support greater use of cash vouchers to promote COVID-19 vaccine uptake and do not support the use of lottery incentives.
CC- chemokine ligand 25 mediates inflammatory crosstalk between adipose and liver in non-alcoholic fatty liver disease
Authors: Parker Richard , Drake J , Weston CJ , Adams DH 
Published: July 2021

AbstractBackground and AimsObesity is closely associated with non-alcoholic fatty liver disease (NAFLD). We investigated expression of the CC-chemokine CCL25 in adipose tissue (AT) and its relation to hepatic inflammation.MethodsPrimary human tissue was used for all experiments. CCL25 concentration in serum was measured with enzyme-linked immunosorbent assay (ELISA). Gene expression of CCL25 was measured with polymerase chain reaction. Protein expression was assessed with ELISA and immunohistochemistry. Leukocyte trafficking was investigated in a dynamic assay to model the hepatic sinusoid. Expression of CCR9 on liver-infiltrating leukocytes analysed with flow cytometry.ResultsCirculating CCL25 was increased in obesity. Gene expression of CCL25 in AT was several-fold higher than in liver, although protein levels of CCL25 were comparable. Soluble CCL25 in flow media increased leukocyte trafficking across hepatic endothelium. Greater numbers of CCR9+ cells were seen in liver tissue from patients with NAFLD, where the greatest difference was in the number of CD14+CD16+ monocytes.ConclusionsCCL25 and its cognate receptor CCR9 mediate a novel pathway of inflammatory crosstalk between adipose and liver tissue in NAFLD.
Immune responses to a single dose of the AZD1222/Covishield vaccine at 16 weeks in individuals in Sri Lanka
Authors: Jeewandara Chandima , Guruge Dinuka , Pushpakumara Pradeep Darshana , Kamaladasa Achala , Aberathna Inoka Sepali , Tanussiya Shyrar , Banuri Gunasekera B , Wijesinghe Ayesha , Dissanayake Osanda , Kuruppu Heshan , Ranasinghe Thushali , Jayathilaka Deshni , Dayarathna Shashika , Ekanayake Dinithi , Jayamali MPDJ , Gamalath Nayanathara , Mudumkotuwa Anushika , Somathilake Gayasha , Dissanayake Madhushika , Harvie Michael , Nimasha Thashmi , Madusanka Deshan , Jayadas Tibutius , Wijayamuni Ruwan , Schimanski Lisa , Rijal Pramila , Tan Tiong .K. , Townsend Alain , Ogg Graham S. , Malavige Gathsaurie Neelika 
Published: July 2021

AbstractIntroductionDue to limited access to vaccines, many countries have only administered a single dose of the AZD1222, while the dosage intervals have increased ≥ weeks. We sought to investigate the immunogenicity of a single dose of vaccine at ≥ 16 weeks.MethodsSARS-CoV-2 specific antibodies in 553 individuals and antibodies to the receptor binding domain (RBD) of the Wuhan virus (WT) and the variants of concern (VOCs), ACE2 receptor blocking antibodies, ex vivo and cultured IFNγ T cell responses and B cell ELISpot responses were investigated in a sub-cohort.ResultsThe seropositivity rates in those >70 years of age (93.7%) was not significantly different compared to other age groups (97.7 to 98.2, Pearson Chi-Square = 7.8, p-value = 0.05). The antibody titres (antibody index) significantly declined (p<0.0001) with increase in age. 18/69 (26.1%) of individuals did not have ACE2 receptor blocking antibodies, while responses to the RBD of WT (p=0.03), B.1.1.7 (p=0.04) and B.1.617.2 (p=0.02) were significantly lower in those who were >60 years. Ex vivo IFN γ T cell ELISpot responses were seen in 10/66 (15.1%), while only a few expressed CD107a. However, >85% had a high frequency of cultured IFNγ T cell ELISpot responses and B cell ELISpots.ConclusionVirus specific antibodies were maintained at ≥ 16 weeks after receiving a single dose of AZD1222, although levels were lower to VOCs, especially in older individuals. A single dose induced a high frequency of memory T and B cell responses.
Vaccine effectiveness when combining the ChAdOx1 vaccine as the first dose with an mRNA COVID-19 vaccine as the second dose
Authors: Gram Mie Agermose , Nielsen Jens , Schelde Astrid Blicher , Nielsen Katrine Finderup , Moustsen-Helms Ida Rask , Bjørkholt Sørensen Anne Katrine , Valentiner-Branth Palle , Emborg Hanne-Dorthe 
Published: July 2021

AbstractBackgroundThe recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different vaccine types, which necessitates new knowledge on vaccine effectiveness (VE). In this study, we aimed to estimate the VE when combining the ChAdOx1 vaccine as the first dose and an mRNA vaccine as the second dose.MethodsThis nationwide population-based cohort study estimated VE against SARS-CoV-2 infection, all-cause and COVID-19 related hospitalization and death after receiving the ChAdOx1 vaccine as the first dose followed by an mRNA vaccine as the second dose. VE estimates were obtained using a Cox regression with calendar time as underlying time and adjusted for sex, age, comorbidity, heritage and hospital admission. Information on all individuals was extracted and linked from high-quality national registries.ResultsA total of 5,542,079 individuals were included in the analyses (97.6% of the total Danish population). A total of 144,360 were vaccinated with the ChAdOx1 vaccine as the first dose and of these 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 cases of SARS-CoV-2 infection were included. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% confidence interval (CI): 83; 92) 14 days after the second dose and onwards. There were no COVID-19 related hospitalizations and deaths among the individuals vaccinated with the combination of the ChAdOx1 and an mRNA vaccine during the study period.ConclusionIn conclusion, this study found a reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals. This is similar to the VE of two doses of an mRNA vaccine. Longer follow-up time is needed to confirm vaccine induced protection against severe events, such as COVID-19 related hospitalization and death.
Higher serological responses and increased vaccine effectiveness demonstrate the value of extended vaccine schedules in combatting COVID-19 in England
Authors: Amirthalingam Gayatri , Bernal Jamie Lopez , Andrews Nick J , Whitaker Heather , Gower Charlotte , Stowe Julia , Tessier Elise , Subbarao Vani , Ireland Georgina , Baawuah Frances , Linley Ezra , Warrener Lenesha , O’Brien Michelle , Whillock Corinne , Moss Paul , Ladhani Shamez N , Brown Kevin E , Ramsay Mary E 
Published: July 2021

AbstractIntroductionIn January 2021, the UK decided to prioritise the delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval until the second dose up to 12 weeks.MethodsSerological responses were compared after BNT162b2 and AZD1222 vaccination with varying intervals in uninfected and previously-infected adults aged 50-89 years. These findings are evaluated against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England.ResultsWe recruited 750 participants aged 50-89 years, including 126 (16.8%) with evidence of previous infection; 421 received BNT162b2 and 329 and AZD1222. For both vaccines, over 95% had seroconverted 35-55 days after dose one, and 100% seroconverted 7+ days after dose 2. Following a 65-84 day interval between two doses, geometric mean titres (GMTs) at 14-34 days were 6-fold higher for BNT162b2 (6703; 95%CI, 5887-7633) than AZD1222 (1093; 806-1483), which in turn were higher than those receiving BNT162b2 19-29 days apart (694; 540 - 893). For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with interval between doses. Higher two-dose VE was observed with >6 week intervals between BNT162b2 doses compared to the authorised 3-week schedule, including ≥80 year-olds.ConclusionOur findings support the UK approach of prioritising the first dose of COVID-19 vaccines, with evidence of higher protection following extended schedules. Given global vaccine constraints, these results are relevant to policymakers, especially with highly transmissible variants and rising incidence in many countries.FundingPublic Health England
ESCRT-I controls lysosomal membrane protein homeostasis and restricts MCOLN1-dependent TFEB/TFE3 signaling
Authors: Wróbel Marta , Szymańska Ewelina , Budick-Harmelin Noga , Kolmus Krzysztof , Goryca Krzysztof , Dąbrowska Michalina , Paziewska Agnieszka , Mikula Michał , Cendrowski Jarosław , Miączyńska Marta 
Published: July 2021

AbstractWithin the endolysosomal pathway in mammalian cells, ESCRT complexes facilitate degradation of proteins residing in endosomal membranes. Recent studies revealed that yeast ESCRT machinery also sorts ubiquitinated proteins from the vacuolar membrane for degradation in the vacuole lumen. However, whether mammalian ESCRTs perform a similar function at lysosomes remained unknown. Here, we show that ESCRT-I restricts the size of lysosomes and promotes degradation of proteins from lysosomal membranes, including MCOLN1, a Ca2+ channel protein. Upon ESCRT-I depletion, the lysosomal accumulation of non-degraded proteins coincided with elevated expression of genes annotated to cholesterol biosynthesis and biogenesis of lysosomes, indicative of response to lysosomal stress. Accordingly, the lack of ESCRT-I promoted abnormal cholesterol accumulation in lysosomes and activated TFEB/TFE3 transcription factors. Finally, we discovered that in contrast to basal TFEB/TFE3 signaling that depended on the availability of exogenous lipids, the stress-induced activation of this pathway was Ca2+-MCOLN1-dependent. Hence, we provide evidence that ESCRT-I is crucial for maintaining lysosomal homeostasis and we elucidate mechanisms distinguishing basal from lysosomal stress-induced TFEB/TFE3 signaling.
The role of trade-offs and feedbacks in shaping integrated plasticity and behavioral correlations
Authors: Dochtermann Ned A. 
Published: July 2021

ABSTRACTHow behaviors vary among individuals and covary with other behaviors has been a major topic of interest over the last two decades. Unfortunately, proposed theoretical and conceptual frameworks explaining the seemingly ubiquitous observation of behavioral (co)variation have rarely successfully generalized. Two observations perhaps explain this failure: First, phenotypic correlations between behaviors are more strongly influenced by correlated and reversible plastic changes in behavior than by “behavioral syndromes”. Second, while trait correlations are frequently assumed to arise via trade-offs, the observed pattern of correlations is not consistent with simple pair-wise trade-offs. A possible resolution to the apparent inconsistency between observed correlations and a role for trade-offs is provided by state-behavior feedbacks. This is critical because the inconsistency between data and theory represents a major failure in our understanding of behavioral evolution. These two primary observations emphasize the importance of an increased research focus on correlated reversible plasticity in behavior—frequently estimated and then disregarded as within-individual covariances.LAY SUMMARYCorrelations between behaviors are common but observed patterns of these correlations are, at least superficially, inconsistent with expectations of trade-offs. This mismatch is potentially resolved via feedbacks between behaviors and energy availability, suggesting important new research directions.DATA AND MODEL AVAILABILITYModel code, as well as the data associated with Figures 2 & 3, are available at github.com/DochtermannLab/FeedbacksModel. Both code and data will be made available at Dryad if accepted.
Site-specific recognition of SARS-CoV-2 nsp1 protein with a tailored titanium dioxide nanoparticle
Authors: Agback P. , Agback T. , Dominguez F. , Frolova E.I. , Seisenbaeva G. , Kessler V. 
Published: July 2021

AbstractThe ongoing world-wide Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic shows the need for new sensing and therapeutic means against the CoV viruses. The SARS-CoV-2 nsp1 protein is important, both for replication and pathogenesis, making it an attractive target for intervention. In recent years nanoparticles have been shown to interact with peptides, ranging in size from single amino acids up to proteins. These nanoparticles can be tailor-made with specific functions and properties including bioavailability. To the best of our knowledge, in this study we show for the first time that a tailored titanium oxide nanoparticle interacts specifically with a unique site of the full-length SARS-CoV-2 nsp1 protein. This can be developed potentially into a tool for selective control of viral protein functions.
Application of Modular Response Analysis to Medium- to Large-Size Biological Systems
Authors: Mekedem Meriem , Ravel Patrice , Colinge Jacques 
Published: July 2021

AbstractThe development of high-throughput genomic technologies associated with recent genetic perturbation techniques such as short hairpin RNA (shRNA), gene trapping, or gene editing (CRISPR/Cas9) has made it possible to obtain large perturbation data sets. These data sets are invaluable sources of information regarding the function of genes, and they offer unique opportunities to reverse engineer gene regulatory networks in specific cell types. Modular response analysis (MRA) is a well-accepted mathematical modeling method that is precisely aimed at such network inference tasks, but its use has been limited to rather small biological systems so far. In this study, we show that MRA can be employed on large systems with almost 1,000 network components. In particular, we show that MRA performance surpasses general-purpose mutual information-based algorithms. Part of these competitive results was obtained by the application of a novel heuristic that pruned MRA-inferred interactionsa posteriori. We also exploited a block structure in MRA linear algebra to parallelize large system resolutions.Author SummaryThe knowledge of gene and protein regulatory networks in specific cell types, including pathologic cells, is an important endeavor in the post-genomic era. A particular type of data obtained through the systematic perturbation of the actors of such networks enables the reconstruction of the latter and is becoming available at a large scale (networks comprised of almost 1,000 genes). In this work, we benchmark the performance of a classical methodology for such data called modular response analysis, which has been so far applied to networks of modest sizes. We also propose improvements to increase performance and to accelerate computations on large problems.
MAFB surrogates the glucocorticoid receptor ability to induce tolerogenesis in dendritic cells
Authors: Morante-Palacios Octavio , Ciudad Laura , Micheroli Raphael , de la Calle-Fabregat Carlos , Li Tianlu , Barbisan Gisela , Houtman Miranda , Edalat Sam , Frank-Bertoncelj Mojca , Ospelt Caroline , Ballestar Esteban 
Published: July 2021

AbstractGlucocorticoids (GCs) exert potent anti-inflammatory effects in immune cells through the glucocorticoid receptor (GR). Dendritic cells (DCs), central actors for coordinating immune responses, acquire tolerogenic properties in response to GCs. Tolerogenic DCs (tolDCs) have emerged as a potential treatment for various inflammatory diseases. To date, the underlying cell type-specific regulatory mechanisms orchestrating GC-mediated acquisition of immunosuppressive properties remain poorly understood. In this study, we investigated the transcriptomic and epigenomic remodeling associated with differentiation to DCs in the presence of GCs. Our analysis demonstrates a major role of MAFB in this process, in synergy with GR. GR and MAFB both interact with methylcytosine dioxygenase TET2 and bind to genomic loci that undergo specific demethylation in tolDCs. We also show that the role of MAFB is more extensive, binding to thousands of genomic loci in tolDCs. Finally, MAFB knockdown erases the tolerogenic properties of tolDCs and reverts the specific DNA demethylation and gene upregulation. The preeminent role of MAFB is also demonstrated in vivo for myeloid cells from synovium in rheumatoid arthritis following GC treatment. Our results imply that, once directly activated by GR, MAFB takes over the main roles to orchestrate the epigenomic and transcriptomic remodeling that define the tolerogenic phenotype.
Isolating the Sources of Pipeline-Variability in Group-Level Task-fMRI results
Authors: Bowring Alexander , Nichols Thomas E. , Maumet Camille 
Published: July 2021

AbstractWhile the development of tools and techniques has broadened our horizons for comprehending the complexities of the human brain, a growing body of research has highlighted the pitfalls of such methodological plurality. In a recent study, we found that the choice of software package used to run the analysis pipeline can have a considerable impact on the final group-level results of a task-fMRI investigation (Bowring et al., 2019, BMN). Here we revisit our work, seeking to identify the stages of the pipeline where the greatest variation between analysis software is induced. We carry out further analyses on the three datasets evaluated in BMN, employing a common processing strategy across parts of the analysis workflow and then utilizing procedures from three software packages (AFNI, FSL and SPM) across the remaining steps of the pipeline. We use quantitative methods to compare the statistical maps and isolate the main stages of the workflow where the three packages diverge. Across all datasets, we find that variation between the packages’ results is largely attributable to a handful of individual analysis stages, and that these sources of variability were heterogeneous across the datasets (e.g. choice of first-level signal model had the most impact for the ds000001 dataset, while first-level noise model was more influential for ds000109 dataset). We also observe areas of the analysis workflow where changing the software package causes minimal differences in the final results, finding that the group-level results were largely unaffected by which software package is used to model the low-frequency fMRI drifts.