bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infectious SARS-CoV-2 Virus in Symptomatic COVID-19 Outpatients: Host, Disease, and Viral Correlates
Authors: Mollan Katie R. , Eron Joseph J. , Krajewski Taylor J. , Painter Wendy , Duke Elizabeth R. , Morse Caryn G. , Goecker Erin A. , Premkumar Lakshmanane , Wolfe Cameron R. , Szewczyk Laura J. , Alabanza Paul L. , Loftis Amy James , Degli-Angeli Emily J. , Brown Ariane J. , Dragavon Joan A. , Won John J. , Keys Jessica , Hudgens Michael G. , Fang Lei , Wohl David A. , Cohen Myron S. , Baric Ralph S. , Coombs Robert W. , Sheahan Timothy P. , Fischer William A. 
Published: June 2021

AbstractBackgroundWhile SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection.MethodsCOVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay.ResultsAmong 204 participants with mild-to-moderate symptomatic COVID19, the median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (IgA, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001).ConclusionsThe presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion.ClinicalTrials.gov IdentifierNCT04405570Key Points (Summary)Among COVID-19 outpatients within 7 days of symptom onset, the presence of SARS-CoV-2-specific antibodies was strongly associated with clearance of infectious virus. Seropositivity appears to be more reliable marker of infectious virus clearance than subjective measure of COVID-19 symptoms.
Robust Characterization of Non-Invasive Post-Traumatic Osteoarthritis Mouse Model
Authors: Bhatti Fazal-Ur-Rehman , Jeong Yong-Hoon , Kim Do-Gyoon , Brand David D. , Hasty Karen A. , Cho Hongsik 
Published: May 2021

AbstractObjectiveBiochemical and molecular changes involved in the pathophysiology of post-traumatic arthritis (PTOA) have not been fully understood. This study used non-invasive mouse models to study biochemical, biomechanical and pain-related behavior changes induced in mice following repetitive mechanical knee loading. Mouse models were used to reflect the effects of the early stages of PTOA in humans.MethodsForty-eight twelve week old male mice were obtained for three groups: normal control without mechanical loading, trauma (24 hours after loading), and PTOA (early OA) groups. For the non-invasive PTOA mouse model, cyclic comprehensive loading (9 N) was applied on the left knee joint of each mouse. Biochemical and molecular changes induced by mechanical loading were analyzed after loading was completed. Blood and cartilage were collected and further examined using gene expression analysis. Grading of the tissue sections was completed using the osteoarthritis research society international (OARSI) scale. Biomechanical features of mechanically loaded knee joints were determined after 24 hours (Trauma) and three weeks (PTOA) post-mechanical loading sessions to examine the development of PTOA, respectively.ResultsThe loaded left knee joint showed a greater ROS/RNS signal than the right knee that was not loaded. There was an increase in cartilage damage and MMP activity in the affected knee as the intensity of MabCII680 and MMP750 signal increased in the mechanical loaded joints as compared to unloaded control knee joints. There was also an increase in the difference of viscoelastic energy dissipation ability (tan δ) in PTOA. The OA score increased significantly in mechanically loaded knee joints.ConclusionThis study showed that biomechanical, biochemical, and behavioral characteristics of the murine PTOA groups are significantly different from the control group. These results validate that the current mouse model can be used for translational studies to examine PTOA.
Association between individual and country-level socioeconomic factors and work participation in spondyloarthritis including psoriatic arthritis: analysis of the ASAS-perSpA study
Authors: Zhao Sizheng Steven , Nikiphorou Elena , Boonen Annelies , López-Medina Clementina , Dougados Maxime , Ramiro Sofia 
Published: June 2021

AbstractObjectiveTo examine whether associations between socioeconomic factors and work outcomes in spondyloarthritis (SpA) differ across axial (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA), and whether associations for individual-level socioeconomic factors are modified by country-level factors.MethodsPatients with a physician diagnosis of SpA within working age (18-65 years) were included. Associations between individual- (age, gender, education, marital status) and country-level factors (Human Development Index, Health Care Expenditure (HCE), Gross Domestic Product, percentage unemployed) with work outcomes (employment status, absenteeism, presenteeism) were assessed using multivariable mixed-effects models. Associations between individual factors and outcomes were compared according to SpA phenotypes and country-level factors using interaction terms.ResultsA total of 3835 patients (mean age 42 years, 61% males) from 23 countries worldwide were included (66% axSpA, 10% pSpA, 23% PsA). Being employed was associated with gender (male vs. female OR 2.5; 95%CI 1.9-3.2), education (university vs. primary OR 3.7; 2.9-4.7), marital status (married vs. single OR 1.3; 1.04-1.6), and age in a non-linear manner. University (vs primary) education was associated with lower odds of absenteeism (OR 0.7; 0.5-0.96) and presenteeism (OR 0.5; 0.3-0.7). Associations were similar across SpA phenotypes. Higher HCE was associated with more favourable work outcomes, e.g., higher odds of employment (OR 2.5; 1.5-4.1). Gender discrepancy in odds of employment was greater in countries with lower socioeconomic development.ConclusionHigher educational attainment and higher HCE were associated with more favourable work outcomes, independently of SpA phenotype. The disadvantageous effect of female gender on employment is particularly strong in countries with lower socioeconomic development.
Eosinophils are an integral component of the pulmonary granulocyte response in Tuberculosis and promote host resistance in mice
Authors: Bohrer Andrea C. , Castro Ehydel , Hu Zhidong , Queiroz Artur T.L. , Tocheny Claire E. , Assmann Maike , Sakai Shunsuke , Nelson Christine , Baker Paul J. , Ma Hui , Wang Lin , Zilu Wen , du Bruyn Elsa , Riou Catherine , Kauffman Keith D. ,   Tuberculosis Imaging Program, Moore Ian N. , Nonno Franca Del , Petrone Linda , Goletti Delia , Martineau Adrian R. , Lowe David M. , Cronan Mark R. , Wilkinson Robert J. , Barry Clifton E. , Via Laura E. , Barber Daniel L. , Klion Amy D. , Andrade Bruno B. , Song Yanzheng , Wong Ka-Wing , Mayer-Barber Katrin D. 
Published: June 2021

ABSTRACTHost resistance to Mycobacterium tuberculosis infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. Influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, employing complementary genetic models of eosinophil deficiency, we demonstrate that, in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice.
Biofouling Characteristics of Graphene Oxide Membrane in a Protein-rich Environment
Authors: Rode Richard , Moghaddam Saeed 
Published: May 2021

AbstractMembrane biofouling has inhibited permselective separation processes for decades, requiring frequent membrane backwash treatment or replacement to maintain efficacy. However, frequent treatment is not viable for devices with a continuous blood flow such as a wearable or implantable dialyzer. In this study, the biofouling characteristics of a highly hemocompatible graphene oxide (GO) membrane developed through a novel self-assembly process is studied in a protein-rich environment and compared with performance of a state-of-the-art commercial polymer membrane dialyzer. The studies are conducted in phosphate-buffered saline (PBS) environment using human serum albumin (HSA), which represents 60% of the blood protein, at the nominal blood protein concentration of 1 g L-1. Protein aggregation on the membrane surface is evaluated by monitoring the change in the membrane flux and SEM imaging. The GO membrane water flux declined only ~10% over a week-long test whereas the polymer membrane flux declined by 50% during the same period. The SEM images show that HSA primarily aggerates over the graphitic regions of nanoplatelets, away from the charged hydrophilic edges. This phenomenon leaves the open areas of the membrane formed between the nanoplatelets edges, through which the species pass, relatively intact. In contrast, HSA completely plugs the polymer membrane pores resulting in a steady decline in membrane permeability.
Aerosol SARS-CoV-2 in hospitals and long-term care homes during the COVID-19 pandemic
Authors: Mallach Gary , Kasloff Samantha B. , Kovesi Tom , Kumar Anand , Kulka Ryan , Krishnan Jay , Robert Benoit , McGuinty Michaeline , Otter-Moore Sophia den , Yazji Bashour , Cutts Todd 
Published: June 2021

AbstractBackgroundFew studies have quantified aerosol concentrations of SARS-CoV-2 in hospitals and long-term care homes, and fewer still have examined samples for viability. This information is needed to clarify transmission risks beyond close contact.MethodsWe deployed particulate air samplers in rooms with COVID-19 positive patients in hospital ward and ICU rooms, rooms in long-term care homes experiencing outbreaks, and a correctional facility experiencing an outbreak. Samplers were placed between 2 and 3 meters from the patient. Aerosol (small liquid particles suspended in air) samples were collected onto gelatin filters by Ultrasonic Personal Air Samplers (UPAS) fitted with <2.5µm (micrometer) and <10 µm size-selective inlets operated for 16 hours (total 1.92m3), and with a Coriolis Biosampler over 10 minutes (total 1.5m3). Samples were assayed for viable SARS-CoV-2 virus and for the viral genome by multiplex PCR using the E and N protein target sequences. We validated the sampling methods by inoculating gelatin filters with viable vesicular stomatitis virus (VSV), and with three concentrations of viable SARS-CoV-2, operating personal samplers for 16hrs, and quantifying viable virus recovery by TCID50 assay.ResultsIn total, 138 samples were collected from 99 rooms. RNA samples were positive in 9.1% (6/66) of samples obtained with the UPAS 2.5µm samplers, 13.5% (7/52) with the UPAS 10µm samplers, and 10.0% (2/20) samples obtained with the Coriolis samplers. Culturable virus was not recovered in any samples. Viral RNA was detected in 10.9% of the rooms sampled. There was no significant difference in viral RNA recovery between the different room locations or samplers. Method development experiments indicated minimal loss of SARS-CoV-2 viability via the personal air sampler operation.Key FindingsAlthough a subset of aerosol samples exhibited detectable SARS-CoV-2 RNA at low titres, the presence of viable SARS-CoV-2 virus in aerosols appears to be infrequent at >2m distance.
Correlation of vaccine-elicited antibody levels and neutralizing activities against SARS-CoV-2 and its variants
Authors: Liu Jinbiao , Bodnar Brittany H , Wang Xu , Wang Peng , Meng Fengzhen , Khan Adil I , Saribas A Sami , Padhiar Nigam H , McCluskey Elizabeth , Shah Sahil , Luo Jin Jun , Hu Wen-Hui , Ho Wen-Zhe 
Published: June 2021

AbstractBoth Pfizer-BNT162b2 and Moderna-mRNA-1273 vaccines can elicit an effective immune response against SARS-CoV-2 infection. However, the elicited serum antibody levels vary substantially and longitudinally decrease after vaccination. We examined the correlation of vaccination-induced IgG levels and neutralization titers against newly emerged variants remains and demonstrate a significant reduction of neutralization activities against the variants (B.1.1.7, B.1.525, and B.1.351) in Pfizer or Moderna vaccined sera. There was a significant and positive correlation between serum IgG levels and ID50 titers for not only SARS-CoV-2 WT but also the variants. These findings indicate that a high level of anti-spike IgG may offer better protection against infection from SARS-CoV-2 and its variants. Therefore, it is necessary to longitudinally monitor specific serum IgG level for evaluating the protective efficacy of the vaccines against SARS-CoV-2 and its new variants.
Breaching the cell-envelope barriers of gram-positive and fungal microbes by a type VI secretion system in Acidovorax citrulli
Authors: Pei Tong-Tong , Kan Yumin , Wang Zeng-Hang , Tang Ming-Xuan , Li Hao , Yan Shuangquan , Cui Yang , Zheng Hao-Yu , Luo Han , Dong Tao G. 
Published: May 2021

AbstractThe type VI secretion system (T6SS) is a double-tubular toxin-injection nanomachine widely found in gram-negative human and plant pathogens. The current model depicts that the T6SS spear-like Hcp tube is powered by the contraction of an outer sheath to drill through the envelope of a neighboring cell, achieving cytosol to cytosol delivery. However, gram-positive bacteria seem to be impenetrable to such T6SS action. Here we report that a plant pathogen Acidovorax citrulli (AC) deploys a highly potent T6SS to kill a range of bacteria including Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Mycobacterium smegmatis as well as fungal species including Candida albicans and Pichia pastoris. Using bioinformatic and biochemical assays, we identified a group of T6SS effectors and characterized one effector RhsB that is critical for interspecies interaction. We report that RhsB contains a conserved YD-repeat domain and a C-terminal nuclease domain. Toxicity of RhsB was neutralized by its downstream immunity proteins through direct interaction. RhsB was cleaved at the C-terminal end and a catalytic mutation within the internal aspartic protease abolished such cleavage. Collectively, the T6SS of AC displays potent activities to penetrate the cell envelope barriers of gram-positive and fungal species, highlighting the greatly expanded capabilities of T6SS in modulating microbiome compositions in complex environments.
The genetic impact of an Ebola outbreak on a wild gorilla population
Authors: Fontsere Claudia , Frandsen Peter , Hernandez-Rodriguez Jessica , Niemann Jonas , Scharff-Olsen Camilla Hjorth , Vallet Dominique , Gouar Pascaline Le , Ménard Nelly , Navarro Arcadi , Siegismund Hans R. , Hvilsom Christina , Gilbert M. Thomas P. , Kuhlwilm Martin , Hughes David , Marques-Bonet Tomas 
Published: June 2021

AbstractBackgroundNumerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population.ResultsAssociations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival.ConclusionThis study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival.
Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP
Authors: Carbone Christine E. , Loveland Anna B. , Gamper Howard , Hou Ya-Ming , Demo Gabriel , Korostelev Andrei A. 
Published: June 2021

AbstractDuring translation, a conserved GTPase elongation factor—EF-G in bacteria or eEF2 in eukaryotes—translocates tRNA and mRNA through the ribosome. EF-G has been proposed to act as a flexible motor that propels tRNA and mRNA movement, as a rigid pawl that biases unidirectional translocation resulting from ribosome rearrangements, or by various combinations of motor- and pawl-like mechanisms. Using time-resolved cryo-EM, we visualized GTP-catalyzed translocation without inhibitors, capturing elusive structures of ribosome•EF-G intermediates at near-atomic resolution. Prior to translocation, EF-G binds near peptidyl-tRNA, while the rotated 30S subunit stabilizes the EF-G GTPase center. Reverse 30S rotation releases Pi and translocates peptidyl-tRNA and EF-G by ∼20 Å. An additional 4-Å translocation initiates EF-G dissociation from a transient ribosome state with highly swiveled 30S head. The structures visualize how nearly rigid EF-G rectifies inherent and spontaneous ribosomal dynamics into tRNA-mRNA translocation, whereas GTP hydrolysis and Pi release drive EF-G dissociation.
Prediction of residue-specific contributions to binding and thermal stability using yeast surface display
Authors: Ahmed Shahbaz , Bhasin Munmun , Manjunath Kavyashree , Varadarajan Raghavan 
Published: June 2021

AbstractAccurate prediction of residue burial as well as quantitative prediction of residue-specific contributions to protein stability and activity is challenging, especially in the absence of experimental structural information. This is important for prediction and understanding of disease causing mutations, and for protein stabilization and design. Using yeast surface display of a saturation mutagenesis library of the bacterial toxin CcdB, we probe the relationship between ligand binding and expression level of displayed protein, within vivosolubility inE.coliandin vitrothermal stability. We find that both the stability and solubility correlate well with the total amount of active protein on the yeast cell surface but not with total amount of expressed protein. We coupled FACS and deep sequencing to reconstruct the binding and expression mean fluorescent intensity of each mutant. The reconstructed mean fluorescence intensity (MFIseq) was used to differentiate between buried site, exposed non active-site and exposed active-site positions with high accuracy. The MFIseqwas also used as a criterion to identify destabilized as well as stabilized mutants in the library, and to predict the melting temperatures of destabilized mutants. These predictions were experimentally validated and were more accurate than those of various computational predictors. The approach was extended to successfully identify buried and active-site residues in the receptor binding domain of the spike protein of SARS-CoV-2, suggesting it has general applicability.
Microfabricated disk technology: rapid scale up in midbrain organoid generation
Authors: Mohamed Nguyen-Vi , Lépine Paula , Lacalle-Aurioles María , Sirois Julien , Mathur Meghna , Reintsch Wolfgang , Beitel Lenore K. , Fon Edward A. , Durcan Thomas M. 
Published: June 2021

ABSTRACTBy providing a three-dimensional in vitro culture system with key features of the substantia nigra region in the brain, 3D neuronal organoids derived from human induced pluripotent stem cells (iPSCs) provide living neuronal tissue resembling the midbrain region of the brain. However, a major limitation of conventional brain organoid culture is that it is often labor-intensive, requiring highly specialized personnel for moderate throughput. Additionally, the methods published for long-term cultures require time-consuming maintenance to generate brain organoids in large numbers. With the increasing need for human midbrain organoids (hMOs) to better understand and model Parkinson’s disease (PD) in a dish, there is a need to implement new workflows and methods to both generate and maintain hMOs, while minimizing batch to batch variation. In this study, we developed a method with microfabricated disks to scale up the generation of hMOs. This opens up the possibility to generate larger numbers of hMOs, in a manner that minimizes the amount of labor required, while decreasing variability and maintaining the viability of these hMOs over time. Taken together, producing hMOs in this manner opens up the potential for these to be used to further PD studies.
A low repeated dose of Δ9-tetrahydrocannabinol affects memory performance through serotonergic signalling in mice
Authors: Galera-López Lorena , Salgado-Mendialdúa Victòria , Moreno Estefanía , Bergadà-Martínez Araceli , Hoffman Alexander F. , Manzanares-Sierra Irene , Busquets-Garcia Arnau , Casadó Vicent , Lupica Carl R. , Maldonado Rafael , Ozaita Andrés 
Published: June 2021

AbstractCannabis is the most widely used illicit drug worldwide. Its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), acts as a partial agonist of the main cannabinoid receptor in the brain, the cannabinoid type-1 receptor (CB1R), that is responsible for the central effects of THC including memory impairment. CB1Rs may form heterodimers with the serotonin 5-HT2A receptor (5-HT2AR) which were found responsible for the memory impairment produced by acute high dose of THC in mice. In this study we investigated whether a repeated low dose of THC (1 mg/kg), with no acute consequence on memory performance, could eventually have deleterious cognitive effects. We found that this dose of THC impaired novel object-recognition memory and fear conditioning memory 24 h after the last of 7 consecutive daily treatments. At that time, a general enhancement of c-Fos expression was also observed in several brain regions of THC-exposed animals, as well as a decreased dendritic spine density on hippocampal CA1 pyramidal neurons that was accompanied by reduced long-term potentiation (LTP) at Schaffer collateral-CA1 synapses. Interestingly, an up-regulation in the expression of CB1R/5-HT2AR heterodimers was observed in the hippocampus after THC exposure and pre-treatment with the 5-HT2AR antagonist MDL 100,907 (0.01 mg/kg) prevented the enhanced heterodimerization and the THC-associated memory impairment. Together, these results reveal the significance of serotonergic signalling through 5-HT2ARs in the memory-impairing effects of repeated low doses of THC.