bluuebunny/crossref_metadata_2025_split huggingface dataset:
High seroprevalence of Immunoglobulin G (IgG) and IgM antibodies to SARS-CoV-2 in asymptomatic and symptomatic individuals amidst vaccination roll-out in western Kenya
Authors: Awandu Shehu Shagari , Ochieng Alfred , Onyango Benson , Magwanga Richard Odongo , Were Pamella , Ochung Angeline , Okumu Fredrick , Oloo Marceline Adhiambo , Katieno Jim Seth , Lidechi Shirley , Ogutu Fredrick , Awuor Dorothy , Kirungu Joy Nyangasi , Omoto Francis Orata , Midega Justine , Oure Bonface , Nyunja Regina , Muok Eric M O , Munga Steven , Estambale Benson 
Published: July 2022

AbstractBackgroundThe population’s antibody response is a key factor in comprehending SARS-CoV-2 epidemiology. This is especially important in African settings where COVID-19 impact, and vaccination rates are relatively low. This study aimed at characterizing the Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in both SARS-CoV-2 asymptomatic and symptomatic individuals in Kisumu and Siaya counties in Western Kenya using enzyme linked immunosorbent assays.ResultsThe IgG and IgM overall seroprevalence in 98 symptomatic and asymptomatic individuals in western Kenya between December 2021-March 2022 was 76.5% (95% CI =66.9-84.5) and 31.6% (95% CI =22.6-41.8) respectively. In terms of gender, males had slightly higher IgG positivity 87.8% (36/41) than females 68.4% (39/57). Amidst the ongoing vaccination roll-out during the study period, over half of the study participants (55.1%, 95% CI= 44.7-65.2) had not received any vaccine. About one third, (30.6%, 95% CI= 21.7-40.7) of the study participants had been fully vaccinated, with close to a quarter (14.3% 95% CI=8.04-22.8) partially vaccinated. When considering the vaccination status and seroprevalence, out of the 30 fully vaccinated individuals, IgG seropositivity was 86.7% (95% CI =69.3-96.2) and IgM seropositivity was 40% (95% CI =22.7-59.4). Out of the participants that had not been vaccinated at all, IgG seroprevalence was 70.3% (95% CI 56.4-82.0) with 20.4% (95% CI 10.6-33.5) seropositivity of IgM antibodies. SARs-CoV-2 PCR positivity did not significantly predict IgG (p = 0.457 [95% CI 0.514-4.371]) and IgM (p = 0.858 [95% CI 0.350-2.395]) positivity.ConclusionOur data indicate a high seroprevalence of antibodies to SARS-CoV-2 in western Kenya. This suggests larger fraction of the population were infected with SARS-CoV-2 within the defined period than what PCR testing could cover.
Evolution of SARS-CoV-2 Shedding in Exhaled Breath Aerosols
Authors: Lai Jianyu , Coleman Kristen K. , Sheldon Tai S.-H. , German Jennifer , Hong Filbert , Albert Barbara , Esparza Yi , Srikakulapu Aditya K. , Schanz Maria , Maldonado Isabel Sierra , Oertel Molly , Fadul Naja , Gold T. Louie , Weston Stuart , Mullins Kristin , McPhaul Kathleen M. , Frieman Matthew , Milton Donald K. 
Published: July 2022

AbstractAerosol inhalation is increasingly well recognized as a major if not primary mode of transmission of SARS-CoV-21,2. Over the course of the COVID-19 pandemic, three highly transmissible lineages evolved and became globally dominant3. One hypothesis to explain increased transmissibility is that natural selection favours variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. Here, we demonstrate that viral shedding (measured as RNA copies) into exhaled breath aerosol was significantly greater during infections with Alpha, Delta, and Omicron than with ancestral strains and variants not associated with increased transmissibility. The three highly transmissible variants independently evolved a high viral aerosol shedding phenotype, demonstrating convergent evolution. We did not observe statistically significant differences in rates of shedding between Alpha, Delta, and Omicron infections. The highest shedder in our study, however, had an Omicron infection and shed three orders of magnitude more viral RNA copies than the maximum observed for Delta and Alpha4. Our results also show that fully vaccinated and boosted individuals, when infected, can shed infectious SARS-CoV-2 via exhaled breath aerosols. These findings provide additional evidence that inhalation of infectious aerosols is the dominant mode of transmission and emphasize the importance of ventilation, filtration, and air disinfection to mitigate the pandemic and protect vulnerable populations. We anticipate that monitoring aerosol shedding from new SARS-CoV-2 variants and emerging pathogens will be an important component of future threat assessments and will help guide interventions to prevent transmission via inhalation exposure.
The Association of Fear of Movement and Postural Sway in People with Low Back Pain
Authors: Meinke Anita , Maschio Cinzia , Meier Michael , Karlen Walter , Swanenburg Jaap 
Published: July 2022

AbstractBackgroundFear of movement is thought to interfere with the recovery from low back pain (LBP). To date, the relationship between fear of movement and postural balance has not been adequately elucidated. Recent findings suggest that more specific fears need to be assessed and put in relation to a specific movement task. We propose that the fear to bend the trunk in a certain direction is distinctly related to the amount of postural sway in different directions. Therefore, our aim was to investigate whether fear of movement in general and fear of bending the trunk in a certain plane is related to postural sway.MethodsData was collected from participants with LBP during two assessments approximately three weeks apart. Postural sway was measured with a force-platform during quiet standing with the eyes closed. Fear of movement was assessed with an abbreviated version of the Tampa Scale of Kinesiophobia (TSK-11) and custom items referring to fear of bending the trunk in the sagittal and the frontal plane.ResultsBased on data from 25 participants, fear of bending the trunk in the frontal plane was positively related to displacement in the sagittal and frontal plane and to velocity in the frontal plane (X2=4.35, P=.04; X2=8.15, P=.004; X2=9.79, P=.002). Fear of bending the trunk in the sagittal plane was not associated with any direction specific measure of sway. A positive relation of the TSK-11 with velocity of the frontal plane (X2=7.14, P=.008) was found, but no association with undirected measures of sway.DiscussionFear of bending the trunk in the frontal plane may be especially relevant to postural sway under the investigated stance conditions. It is possible that fear of bending the trunk in the frontal plane could interfere with balance control at the hip, shifting the weight from side to side to control balance.ConclusionFor the first time the directional relationship of fear of movement and postural sway was studied. Fear of bending the trunk in the frontal plane was positively associated with several measures of postural sway.
Chromatin accessibility profiling in tissue sections by spatial ATAC
Authors: Llorens-Bobadilla Enric , Zamboni Margherita , Marklund Maja , Bhalla Nayanika , Chen Xinsong , Hartman Johan , Frisén Jonas , Ståhl Patrik L 
Published: July 2022

AbstractCurrent methods for epigenomic profiling are limited in the ability to obtain genome wide information with spatial resolution. Here we introduce spatial ATAC, a method that integrates transposase-accessible chromatin profiling in tissue sections with barcoded solid-phase capture to perform spatially resolved epigenomics. We show that spatial ATAC enables the discovery of the regulatory programs underlying spatial gene expression during mouse organogenesis, lineage differentiation and in human pathological samples.
Regulation of cell size and Wee1 by elevated levels of Cdr2
Authors: Berg Rachel A. , Moseley James B. 
Published: July 2022

AbstractMany cell cycle regulatory proteins catalyze cell cycle progression in a concentration-dependent manner. In fission yeast S. pombe, the protein kinase Cdr2 promotes mitotic entry by organizing cortical oligomeric nodes that lead to inhibition of Wee1, which itself inhibits Cdk1. cdr2Δ cells lack nodes and divide at increased size due to overactive Wee1, but it has not been known how increased Cdr2 levels might impact Wee1 and cell size. Using a Tetracycline-inducible expression system, we found that a 6X increase in Cdr2 expression caused hyperphosphorylation of Wee1 and reduction in cell size. This overexpressed Cdr2 formed clusters that sequestered Wee1 adjacent to the nuclear envelope. Cdr2 mutants that disrupt either kinase activity or clustering ability failed to sequester Wee1 and to reduce cell size. We propose that Cdr2 acts as a dosage-dependent regulator of cell size by sequestering its substrate Wee1 away from Cdk1 in the nucleus. This mechanism has implications for other clustered kinases, which may act similarly by sequestering substrates.
Hierarchical cell-type identifier accurately distinguishes immune-cell subtypes enabling precise profiling of tissue microenvironment with single-cell RNA-sequencing
Authors: Lee Joongho , Kim Minsoo , Kang Keunsoo , Yang Chul-Su , Yoon Seokhyun 
Published: July 2022

AbstractSingle-cell RNA-seq enabled in-depth study on tissue micro-environment and immune-profiling, where a crucial step is to annotate cell identity. Immune cells play key roles in many diseases while their activities are hard to track due to diverse and highly variable nature. Existing cell-type identifiers had limited performance for this purpose. We present HiCAT, a hierarchical, marker-based cell-type identifier utilizing gene set analysis for statistical scoring for given markers. It features successive identification of major-type, minor-type and subsets utilizing subset markers structured in a three-level taxonomy tree. Comparison with manual annotation and pairwise match test showed HiCAT outperforms others in major- and minor-type identification. For subsets, we qualitatively evaluated marker expression profile demonstrating that HiCAT provide most clear immune cell landscape. HiCAT was also used for immune cell profiling in ulcerative colitis and discovered distinct features of the disease in macrophage and T cell subsets that could not be identified previously.
Combined SPT and FCS methods reveal a mechanism of RNAP II oversampling in cell nuclei
Authors: Fournier Marie , Leclerc Pierre , Leray Aymeric , Champelovier Dorian , Agbazahou Florence , Bidaux Gabriel , Furlan Alessandro , Héliot Laurent 
Published: July 2022

ABSTRACTGene expression orchestration is a key question in fundamental and applied research. Different models for transcription regulation were proposed, yet the dynamic regulation of RNA polymerase II (RNAP II) activity remains a matter of debate. To improve our knowledge of this topic, we investigated RNAP II motility in eukaryotic cells by combining Single Particle Tracking (SPT) and Fluorescence Correlation Spectroscopy (FCS) techniques, to take advantage of their different sensitivities in order to analyze together slow and fast molecular movements. Thanks to calibrated samples, we developed a benchmark for quantitative analysis of molecular dynamics, to eliminate the main potential instrumental biases. We applied this workflow to study the diffusion of RPB1, the catalytic subunit of RNAP II. By a cross-analysis of FCS and SPT, we could highlight different RPB1 motility states and identifyed a stationary state, a slow diffusion state, and two different modes of subdiffusion. Interestingly, our analysis also unveiled the oversampling by RPB1 of nuclear subdomains. Based on these data, we propose a novel model of spatio-temporal transcription regulation. Altogether, our results highlight the importance of combining microscopy approaches at different time scales to get a full insight into the real complexity of molecular diffusion kinetics in cells.
Retromer oligomerization drives SNX-BAR coat assembly and membrane constriction
Authors: Gopaldass Navin , De Leo Maria Giovanna , Courtellemont Thibault , Mercier Vincent , Bissig Christin , Roux Aurélien , Mayer Andreas 
Published: July 2022

AbstractThe retromer coat mediates protein exit from endosomes and impacts many signaling pathways, lysosomal biogenesis, and diseases such as Parkinson’s, Alzheimer’s and COVID-19. Retromer complexes (CSC in yeast) form coats by interconnecting sorting nexins (SNX). The dynamics of this process is poorly explored. Here, we analyze the oligomerization of CSC/SNX-BAR retromer coats on oriented synthetic lipid tubules. SNX-BARs and CSC assemble a static tubular coat that does not exchange subunits. Coat formation proceeds bidirectionally, adding new subunits at both ends of the coat. High concentrations of SNX-BARs alone suffice to constrict membrane tubes to an invariant radius of 19 nm. At lower concentrations, CSC-complexes must drive constriction, which requires their oligomerization. CSCs populate the SNX-BAR layer at densities that increase with the starting radius of the membrane tube. We hence propose that retromer-mediated crosslinking of SNX-BARs at variable densities tunes the coat according to the energy required to deform the membrane. This model is supported by the effects of mutations interfering with retromer oligomerization, which impair retromer function in yeast and human cells.
Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone
Authors: Zhong Leilei , Lu Jiawei , Fang Jiankang , Yao Lutian , Yu Wei , Gui Tao , Holdreith Nicholas , Bautista Catherine , Choi Yongwon , Jiang Jean X. , Yang Shuying , Tong Wei , Dyment Nathaniel , Qin Ling 
Published: July 2022

AbstractColony stimulating factor 1 (Csf1) is an essential growth factor for osteoclast progenitors and thus an important regulator for bone resorption. It remains elusive which mesenchymal cells synthesizeCsf1stimulating osteoclastogenesis. We recently identified a novel mesenchymal cell population, marrow adipogenic lineage precursors (MALPs), in bone. Single cell RNA- sequencing indicated specific expression ofCsf1in MALPs, which is further increased during aging. To investigate its role, we constructedCsf1 CKOmice usingAdipoq-Cre. These mice showed increased femoral trabecular bone over time, but their cortical bone appeared normal. In comparison, depletion of Csf1 in the entire mesenchymal lineage usingPrx1-Creled to a more striking high bone mass phenotype, suggesting that additional mesenchymal subpopulations secrete Csf1. TRAP staining revealed diminished osteoclasts in the femoral secondary spongiosa region ofCsf1 CKOAdipoqmice, but not at the chondral-osseous junction nor at the endosteal surface of cortical bone. Moreover,Csf1 CKOAdipoqmice were resistant to LPS-induced calvarial osteolysis. Bone marrow cellularity, hematopoietic progenitors, and macrophages were also reduced in these mice. Taken together, our studies demonstrate that MALPs are a critical player in controlling bone remodeling and hematopoiesis.
Metagenomic profiling pipelines improve taxonomic classification for 16S amplicon sequencing data
Authors: Faits Tyler , Odom-Mabey Aubrey R. , Castro-Nallar Eduardo , Crandall Keith A. , Johnson W. Evan 
Published: July 2022

AbstractMost experiments studying bacterial microbiomes rely on the PCR amplification of all or part of the gene for the 16S rRNA subunit, which serves as a biomarker for identifying and quantifying the various taxa present in a microbiome sample. Several computational methods exist for analyzing 16S amplicon-based metagenomics. However, the most-used bioinformatics tools cannot produce quality genus-level or species-level taxonomic calls and may underestimate the degree to which these calls are possible. We used 16S sequencing data from mock bacterial communities to evaluate the sensitivity and specificity of several bioinformatics pipelines and genomic reference libraries used for microbiome analyses, concentrating on measuring the accuracy of species-level taxonomic assignments of 16S amplicon reads. We evaluated the tools Qiime 2, Mothur, PathoScope 2, and Kraken 2 in conjunction with reference libraries from Greengenes, Silva, Kraken, and RefSeq. Profiling tools were compared using publicly available mock community data from several sources, comprising 136 samples with varied species richness and evenness, several different amplified regions within the 16S gene, and both DNA spike-ins and cDNA from collections of plated cells. PathoScope 2 and Kraken 2, both tools designed for whole-genome metagenomics, outperformed Qiime 2 using the DADA2 plugin and Mothur, both of which are theoretically specialized for 16S analyses.
Hoverfly (Eristalis tenax) pursuit of artificial targets
Authors: Thyselius Malin , Ogawa Yuri , Leibbrandt Richard , Wardill Trevor J. , Gonzalez-Bellido Paloma T. , Nordström Karin 
Published: July 2022

AbstractThe ability to visualize small moving objects is vital for the survival of many animals, as these could represent predators or prey. For example, predatory insects, including dragonflies, robber flies and killer flies, perform elegant, high-speed pursuits of both biological and artificial targets. Many non-predatory insects, including male hoverflies and blowflies, also pursue targets during territorial or courtship interactions. To date, most hoverfly pursuits were studied outdoors. To investigate naturalistic hoverfly (Eristalis tenax) pursuits under more controlled settings, we constructed an indoor arena that was large enough to encourage naturalistic behavior. We presented artificial beads of different sizes, moving at different speeds, and filmed pursuits with two cameras, allowing subsequent 3D reconstruction of the hoverfly and bead position as a function of time. We show that maleE. tenaxhoverflies are unlikely to use strict heuristic rules based on angular size or speed to determine when to start pursuit, at least in our indoor setting. We found that hoverflies pursued faster beads when the trajectory involved flying downwards towards the bead. Furthermore, we show that target pursuit behavior can be broken down into two stages. In the first stage the hoverfly attempts to rapidly decreases the distance to the target by intercepting it at high speed. During the second stage the hoverfly’s forward speed is correlated with the speed of the bead, so that the hoverfly remains close, but without catching it. This may be similar to dragonfly shadowing behavior, previously coined ‘motion camouflage’.
Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice
Authors: Rashidieh Behnam , Bain Amanda Louise , Tria Simon Manuel , Sharma Sowmya , Stewart Cameron Allan , Simmons Jacinta Ley , Apaja Pirjo M. , Duijf Pascal H.G. , Finnie John , Khanna Kum Kum 
Published: July 2022

AbstractαB-Crystallin is a heat shock chaperone protein which binds to misfolded proteins to prevent their aggregation. It is overexpressed in a wide-variety of cancers. Previous studies using human cancer cell lines and human xenograft models have reported tumor suppressor or tumor promoter (oncogene) roles for αB-Crystallin depending on cellular context and environmental conditions. To determine the causal relationship between CRYAB overexpression and cancer, we generated a Cryab overexpression knock-in mouse model. This model revealed that constitutive overexpression of Cryab results in the formation of a variety of lethal spontaneous primary and metastatic tumors in mice. In vivo, the overexpression of Cryab correlated with the upregulation of epithelial-to-mesenchymal (EMT) markers, angiogenesis and some oncogenic proteins including Basigin. In vitro, using E1A/Ras transformed mouse embryonic fibroblasts (MEFs), we observed that the overexpression of Cryab led to the promotion of cell survival via upregulation of Akt signaling and downregulation of pro-apoptotic pathway mediator JNK, with subsequent attenuation of apoptosis as assessed by cleaved caspase-3. Overall, through the generation and characterization of Cryab overexpression model, we provide evidence supporting the role of αB-Crystallin as an oncogene, where its upregulation is sufficient to induce tumors, promote cell survival and inhibit apoptosis.
Challenges and considerations for reproducibility of STARR-seq assays
Authors: Das Maitreya , Hossain Ayaan , Banerjee Deepro , Praul Craig Alan , Girirajan Santhosh 
Published: July 2022

AbstractHigh-throughput methods such as RNA-seq, ChIP-seq and ATAC-seq have well-established guidelines, commercial kits, and analysis pipelines that enable consistency and wider adoption for understanding genome function and regulation. STARR-seq, a popular assay for directly quantifying activity of thousands of enhancer sequences simultaneously, has seen limited standardization across studies. The assay is long with >250 steps, and frequent customization of the protocol and variations in bioinformatics methods raise concerns for reproducibility of STARR-seq studies. Here, we assess each step of the protocol and analysis pipelines from published sources and in-house assays, and identify critical steps and QC checkpoints necessary for reproducibility of the assay. We also provide guidelines for experimental design, protocol scaling, customization, and analysis pipelines for better adoption of the assay. These resources will allow better optimization of STARR-seq for specific research needs, enable comparisons and integration across studies, and improve reproducibility of results.
Impairments in the mechanical effectiveness of reactive balance control strategies during walking in people post-stroke
Authors: Liu Chang , McNitt-Gray Jill L. , Finley James 
Published: August 2022

AbstractPeople post-stroke have an increased risk of falls compared to neurotypical individuals, partly resulting from an inability to generate appropriate reactions to restore balance. However, few studies investigated the effect of paretic deficits on the mechanics of reactive control strategies following forward losses of balance during walking. Here, we characterized the biomechanical consequences of reactive control strategies following perturbations induced by the treadmill belt accelerations. Thirty-eight post-stroke participants and thirteen age-matched and speed-matched neurotypical participants walked on a dual-belt treadmill while receiving perturbations that induced a forward loss of balance. We computed whole-body angular momentum and angular impulse using segment kinematics and reaction forces to quantify the effect of impulse generation by both the leading and trailing limbs in response to perturbations in the sagittal plane. We found that perturbations to the paretic limb led to larger increases in forward angular momentum during the perturbation step than perturbations to the non-paretic limb or to neurotypical individuals. To recover from the forward loss of balance, neurotypical individuals coordinated reaction forces generated by both legs to decrease the forward angular impulse relative to the pre-perturbation step. They first decreased the forward pitch angular impulse during the perturbation step. Then, during the first recovery step, they increased the backward angular impulse by the leading limb and decreased the forward angular impulse by the trailing limb. In contrast to neurotypical participants, people post-stroke did not reduce the forward angular impulse generated by the stance limb during the perturbed step. They also did not increase leading limb angular impulse or decrease the forward trailing limb angular impulse using their paretic limb during the first recovery step. Lastly, post-stroke individuals who scored poorer on clinical assessments of balance and had greater motor impairment made less use of the paretic limb to reduce forward momentum. Overall, these results suggest that paretic deficits limit the ability to recover from forward loss of balance. Future perturbation-based balance training targeting reactive stepping response in stroke populations may benefit from improving the ability to modulate paretic ground reaction forces to better control whole-body dynamics.