bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic comparison of current bioinformatic tools for glycoproteomics data
Authors: Rangel-Angarita Valentina , Mahoney Keira E. , Ince Deniz , Malaker Stacy A. 
Published: March 2022

AbstractGlycosylation is one of the most common post-translational modifications and generates an enormous amount of proteomic diversity; changes in glycosylation are associated with nearly all disease states. Intact glycoproteomics seeks to determine the site-localization and composition of glycans along a protein backbone via mass spectrometry. Following data acquisition, raw files are analyzed using search algorithms to define peptide sequence, glycan composition, and site localization. Glycoproteomics is rapidly expanding, creating the pressing need to establish bioinformatic community standards. Recently, several new search algorithms were released, many of which vary in terms of search strategy, localization system, score cutoffs, and glycan databases, thus warranting a comprehensive comparison of these new programs along with existing programs. Here, we analyzed three common samples: an enriched cell lysate, a mixture of 6 glycoproteins, and a mucin-domain glycoprotein. All raw files were searched with comparable parameters among software and the results were extensively manually validated to compare accuracy and completion of the output. Our results highlight the continued need for manual validation of glycopeptide spectral matches, especially for O-glycopeptides. Despite this, O-Pair outperformed all other programs in correct identification of O-glycopeptides and its localization system proved to be useful. On the other hand, Byonic and pGlyco performed best for N-glycoproteomics; the former was best for proteome-wide searches, but the latter identified more N-glycosites in less complex samples. Overall, we summarize the strengths, weaknesses, and potential improvements for these search algorithms.TOC Figure
Feasibility and Sensitivity of Saliva GeneXpert MTB/RIF Ultra for Tuberculosis Diagnosis in Adults in Uganda
Authors: Byanyima Patrick , Kaswabuli Sylvia , Musisi Emmanuel , Nabakiibi Catherine , Zawedde Josephine , Sanyu Ingvar , Sessolo Abdul , Andama Alfred , Worodria William , Huang Laurence , Davis J. Lucian 
Published: March 2022

ABSTRACTThe objective of this prospective, observational study carried out at China-Uganda Friendship Hospital-Naguru in Kampala, Uganda, was to determine the performance of GeneXpert MTB/RIF Ultra (Xpert) testing on saliva for active tuberculosis (TB) disease among consecutive adults undergoing diagnostic evaluation. We calculated sensitivity to determine the diagnostic performance in comparison to that of the composite reference standard of Mycobacterium tuberculosis liquid and solid cultures on two spot sputum specimens. GeneXpert Ultra on saliva had a sensitivity of 90% (95% confidence interval [CI], 81-96%); this was similar to that of sputum fluorescence smear microscopy (FM) of 87% (95% CI, 77-94%). Sensitivity was 24% lower (95% CI for difference 2-48%, p=0.003) among persons living with HIV (71%, 95%CI 44-90%) than among persons living without HIV (95%, 95%CI 86-99%) and 46% lower (95% CI for difference 14-77%, p<0.0001) among sputum microscopy positive (96%, 95% CI 87-99%) than among sputum microscopy negative patients (50%, 95% CI 19-81%). Semi-quantitative Xpert grade was higher in sputum than in paired saliva samples from the same patient. In conclusion, saliva specimens appear to be feasible and similarly sensitive to sputum for active TB diagnosis using molecular testing, suggesting promise as a non-sputum diagnostic test for active TB in high-burden settings.
Enabling Health Outcomes of Nature-based Interventions: A Systematic Scoping Review
Authors: Nejade Rachel , Grace Daniel , Bowman Leigh R. 
Published: March 2022

AbstractBackgroundThe burden of poor mental health and non-communicable disease is increasing, and some practitioners are turning to nature to provide the solution. Nature-based interventions could offer cost-effective solutions that benefit both human health and the environment by reconnecting individuals with nature. Importantly, the relative success of these interventions depends upon the accessibility of green and blue spaces, and the way in which people engage with them.Aims and ObjectivesA scoping review was conducted to establish the evidence base for nature-based interventions as a treatment for poor mental and physical health, and to assess whether and how enablers influence engagement with natural outdoor environments.MethodsThis scoping review followed the PRISMA-ScR and the associated Cochrane guidelines for scoping reviews. A literature search was performed across five databases and the grey literature, and articles were selected based on key inclusion and exclusion criteria. Exposure was the active engagement with natural environments. The primary outcome was mental health and the secondary outcome was physical health, both defined using established metrics. All data was extracted to a charting table and reported as a narrative synthesis.ResultsThe final analysis included thirty-nine studies. Most of these focused on green spaces, with only five dedicated to blue spaces. Six nature-based health intervention types were identified: (i) educational interventions, (ii) physical activity in nature, (iii) wilderness therapy, (iv) leisure activities, (v) gardening and (vi) changes to the built environment. Of the 39 studies, 92.2% demonstrated consistent improvements across health outcomes when individuals engaged with natural outdoor environments (NOEs). Furthermore, of 153 enablers that were found to influence engagement, 78% facilitated engagement while 22% reduced engagement. Aspects such as the sense of wilderness, accessibility, opportunities for physical activity and the absence of noise/ air pollution all increased engagement.ConclusionFurther research is still needed to establish the magnitude and relative effect of nature- based interventions, as well as to quantify the compounding effect of enablers on mental and physical health. This must be accompanied by a global improvement in study design. Nevertheless, this review has documented the increasing body of heterogeneous evidence in support of NBIs as effective tools to improve mental, physical, and cognitive health outcomes. Enablers that facilitate greater engagement with natural outdoor environments, such as improved biodiversity, sense of wilderness and accessibility, as well as opportunities for physical activity and an absence of pollution, will likely improve the impact of nature-based interventions and further reduce public health inequalities.
Human cell-camouflaged nanomagnetic scavengers restore immune homeostasis in a rodent model with bacteremia
Authors: Park Sung Jin , Kwon Seyong , Lee Min Seok , Jang Bong Hwan , Guzmán-Cedillo Axel E. , Kang Joo H. 
Published: March 2022

AbstractBloodstream infection caused by antimicrobial resistance pathogens is a global concern because it is difficult to treat with conventional therapy. Here we report scavenger magnetic nanoparticles enveloped by nanovesicles derived from blood cells (MNVs), which magnetically eradicate an extreme range of pathogens in an extracorporeal circuit. We quantitatively reveal that glycophorin A and complement receptor (CR) 1 on red blood cell (RBC)-MNVs predominantly capture human fecal bacteria, carbapenem-resistant (CR)E. coli, and extended-spectrum beta-lactamases-positive (ESBL-positive)E. coli, vancomycin-intermediateS. aureus(VISA), endotoxins, and proinflammatory cytokines in human blood. Additionally, CR3 and CR1 on white blood cell-MNVs mainly contribute to depleting the virus envelope proteins of Zika, SARS-CoV-2, and their variants in human blood. Supplementing opsonins into the blood significantly augments the pathogen removal efficiency due to its combinatorial interactions between pathogens and CR1 and CR3 on MNVs. The extracorporeal blood cleansing enables full recovery of lethally infected rodent animals within seven days by treating them twice in series. We also validate that parameters reflecting immune homeostasis, such as blood cell counts, cytokine levels, and transcriptomics changes, are restored in blood of the fatally infected rats after treatment.
Should individuals be paid to participate in mass drug administration to control malaria?
Authors: Fryer Helen , Peyton-Jones Meg 
Published: March 2022

AbstractMass drug administration (MDA) is a malaria control strategy in which antimalarial drugs are offered to a whole community. Although MDA can potentially clear malaria from a community, it is not routinely used in eradication efforts because of ethical concerns and past failures to achieve lasting elimination. One potential means to improving the outcome of MDA is to incentivize individuals to participate, for example, through monetary payments. In this study our aim is to inform the decision to use MDA to eradicate malaria and explore whether individuals should be incentivized to participate. Through the lens of a mathematical model, we clarify how the costs and benefits of MDA are context-dependent. We highlight that in a community experiencing a good improvement in clinical case management – relative to the prevalence of malaria in the community – the addition of MDA can catalyze stable elimination. However, participation rates are critical and individuals who avoid every round of treatment can prevent elimination. We explore how, in this scenario, individual incentives could change the cost-benefit breakdown, measured at three levels – personal, local community and wider community.
Severe Acute Respiratory Coronavirus-2 Antibody and T cell response after a third vaccine dose in hemodialysis patients compared with healthy controls
Authors: Simon Benedikt , Rubey Harald , Gromann Martin , Knopf-Völkerer Astrid , Hemedi Boris , Zehetmayer Sonja , Kirsch Bernhard 
Published: March 2022

1.AbstractHemodialysis patients (HD patients) have a high health risk from Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) infection. In this study, we assess the impact of a third vaccine dose (3D) on antibody levels and T cell response in HD patients and compare the results to those of a healthy control group.We conducted a prospective cohort study consisting of 60 HD patients and 65 healthy controls. All of them received two doses of the Comirnaty mRNA vaccine and a third mRNA vaccine dose (Spikevax or Comirnaty). The SARS-CoV-2 S antibody response in all participants was measured 6 months after the second vaccine dose and 6 to 8 weeks after administration of the 3D. We also assessed INF-γ secretion 6–8 weeks after the 3D in 24 healthy controls, 17 HD patients with a normal and 20 HD patients with a low or no antibody response after the second dose. The groups were compared using univariate quantile regressions and multiple analyses. The adverse effects of vaccines were assessed via a questionnaire.After the 3D, the SARS-CoV-2-specific antibody and INF-γ titers of most HD patients were comparable to those of healthy controls. A subgroup of HD patients who had shown a diminished antibody response after the first two vaccine doses developed a significantly lower antibody and INF-γ response compared to responder HD patients and controls, even after the 3D. A new strategy is needed to protect this patient group from severe COVID-19 infection.
A microfluidic platform to investigate the role of mechanical constraints on tissue reorganization
Authors: Tlili Sham , Graner François , Delanoë-Ayari Hélène 
Published: March 2022

AbstractMechanical constraints have a high impact on development processes, and there is a need for new tools to investigate the role of mechanosensitive pathways in tissue reorganization during development. We present here experiments where embryonic cell aggregates are aspired through constrictions in microfluidic channels, generating highly heterogeneous flows and high cell deformations that can be imaged using two-photon microscopy. This approach provides a way to measure in situ local viscoelastic properties of 3D tissues and connect them to intracellular and intercellular events such as cell shape changes and cell rearrangements. Perspectives include applications on organoids to investigate and quantify rheological properties of tissues, and to understand how constraints affect development.
Surface motility favors co-dependent interaction between Pseudomonas aeruginosa and Burkholderia cenocepacia
Authors: Morin Charles , Landry May , Groleau Marie-Christine , Déziel Eric 
Published: March 2022

AbstractInteractions between different bacterial species shape bacterial communities and their environments. The opportunistic pathogens Pseudomonas aeruginosa and Burkholderia cenocepacia both can colonize the lungs of individuals affected by cystic fibrosis. Using the social surface behavior called swarming motility as a study model of interactions, we noticed intricate interactions between B. cenocepacia K56-2 and P. aeruginosa PA14. While strain K56-2 does not swarm under P. aeruginosa favorable swarming conditions, co-inoculation with a non-motile PA14 flagellum-less ΔfliC mutant restored spreading for both strains. We show that P. aeruginosa provides the wetting agent rhamnolipids allowing K56-2 to perform swarming motility, while aflagellated PA14 seems able to «hitchhike» along with K56-2 cells in the swarming colony.ImportancePseudomonas aeruginosa and Burkholderia cenocepacia are important opportunistic pathogens often found together in the airways of persons with cystic fibrosis. Laboratory co-culture of both species often ends with one taking over the other. We used a surface motility assay to study the social interactions between population of these bacterial species. Under our conditions, B. cenocepacia cannot swarm without supplementation of the wetting agent produced by P. aeruginosa. In a mixed colony of both species, an aflagellated mutant of P. aeruginosa provides the necessary wetting agent to B. cenocepacia, allowing both bacteria to swarm and colonize a surface. We highlight this peculiar interaction where both bacteria set aside their antagonistic tendencies to cooperate.
The cGAS-STING pathway affects vertebral bone but does not promote intervertebral disc cell senescence or degeneration
Authors: Ottone Olivia K. , Kim Cheeho , Collins John. A. , Risbud Makarand V. 
Published: March 2022

AbstractThe DNA-sensing cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP) and mediates type-I interferon inflammatory responses to foreign viral and bacterial DNA as well as self-DNA. Studies of the intervertebral disc in humans and mice demonstrate associations between aging, increased cell senescence, and disc degeneration. Herein we assessed the role of STING in SASP promotion in STING gain- (N153S) and loss-of-function mouse models. N153S mice evidenced elevated circulating levels of proinflammatory markers including IL-1β, IL-6, and TNF-α and exhibited a mild trabecular and cortical bone phenotype in caudal vertebrae. Interestingly, despite systemic inflammation, the structural integrity of the disc and knee articular joint remained intact, and cells did not show a loss of their phenotype or elevated SASP. Transcriptomic analysis of N153S tissues demonstrated an upregulated immune response by disc cells, which did not closely resemble inflammatory changes in human tissues. Interestingly, STING-/-mice also showed a mild vertebral bone phenotype, but the absence of STING did not improve the age-associated disc phenotype or reduce the abundance of SASP markers. Overall, the analyses of N153S and STING-/-mice that the cGAS-STING pathway is not a major contributor to SASP induction and consequent disc aging and degeneration but may play a minor role in the maintenance of trabecular bone in the vertebrae. This work contributes to a growing body of work demonstrating that systemic inflammation is not a key driver of disc degeneration.
Local actuation of organoids by magnetic nanoparticles
Authors: Abdel Fattah Abdel Rahman , Kolaitis Niko , Van Daele Katrien , Rustandi Andika Gregorius , Ranga Adrian 
Published: March 2022

AbstractTissues take shape during development through a series of morphogenetic movements guided by local cell-scale forces. While current in vitro approaches subjecting tissues to homogenous stresses, it is currently no possible to recapitulate highly local spatially varying forces. Here we develop a method for local actuation of organoids using embedded magnetic nanoparticles. Sequential aggregation of magnetically labelled human pluripotent stem cells followed by actuation by a magnetic field produces localized magnetic clusters within the organoid. These clusters impose local mechanical forces on the surrounding tissue in response to applied global magnetic fields. We show that precise, spatially defined actuation provides short-term mechanical tissue perturbations as well as long-term cytoskeleton remodeling. We demonstrate that local magnetically-driven actuation guides asymmetric growth and proliferation, leading to enhanced patterning in human neural organoids. We show that this approach is applicable to other model systems by observing polarized patterning in paraxial mesoderm organoids upon local magnetic actuation. This versatile approach allows for local, controllable mechanical actuation in multicellular constructs, and is widely applicable to interrogate the role of local mechanotransduction in developmental and disease model systems.
Lineage tracing via associative chromosome/plasmid barcoding with siBar
Authors: Mei Han , Nekrutenko Anton 
Published: March 2022

AbstractWe describe a new method, siBar, which enables simultaneous tracking of plasmids and chromosomal lineages within a bacterial host. siBar involves integration of a linearized plasmid construct carrying a unique combination of two molecular barcodes. Upon recircularization one barcode remains integrated into the host chromosome, while the other remains on the plasmid allowing direct observation of expansion and contraction of adaptive lineages. We also performed a pilot evolution experiment that allowed us to assess the barcode complexity and establish an analytical framework for the analysis of siBar data.
A non-invasive method for time-lapse imaging of microbial interactions and biofilm dynamics
Authors: Molina-Santiago Carlos , Pearson John R. , Berlanga-Clavero María Victoria , Pérez-Lorente Alicia Isabel , de Vicente Antonio , Romero Diego 
Published: March 2022

AbstractComplex interactions between microbial populations can greatly affect the overall properties of a microbial community, sometimes leading to cooperation and mutually beneficial coexistence, or to competition and the death or displacement of particular organisms or sub-populations. Interactions between different biofilm populations are highly relevant in diverse scientific areas, from antimicrobial resistance to microbial ecology. The utilization of modern microscopic techniques has provided new and interesting insight into how bacteria interact at the cellular level to form and maintain microbial biofilms. However, our ability to follow complex intra- and inter-species interactions in vivo at the microscopic level has remained somewhat limited. Here, we detail BacLive, a novel non-invasive method for tracking bacterial growth and biofilm dynamics using high resolution fluorescence microscopy and an associated ImageJ processing macro (https://github.com/BacLive) for easier data handling and image analysis. Finally, we provide examples of how BacLive can be used in the analysis of complex bacterial communities.ImportanceCommunication and interactions between single cells are continuously defining the structure and composition of microbial communities timely and spatially. Methods routinely used to the study of these communities at cellular level rely on sample manipulation what deprives from microscopic time lapse experiments on a given sample. BacLive is conceived as a method for the non-invasive study of the formation and development of bacterial communities, such as biofilms, and the dynamics of formation of specialized subpopulations in time-lapse experiments. In addition we prove that BacLive largely simplifies the analysis of the data generated.
Rational design of Cas9 ribonucleoprotein with a “gRNA-shRNA” for multidimensional genome manipulation and enhanced homology-directed repair
Authors: Qiao Jie , Sun Wenli , Yin Wenhao , Ma Lixin , Liu Yi 
Published: March 2022

AbstractGene perturbation approaches have evolved as powerful tools for understanding the function of genes and curing inherited diseases. Here, we develop a method that combines the merits of RNAi and CRISPR technology by rational design of Cas9 ribonucleoprotein (RNP) with a “gRNA-shRNA” component. The RNP, termed Cas9-RNAi, has a gRNA containing a 3’ extension that can be processed to a functional siRNA via dorsha/dicer enzyme mediated cleavage within cells. We prepared the Cas9-RNAi RNPs by streamline co-expression of Cas9 enzymes and the “gRNA-shRNA” ribonucleotides in Escherichia coli strain HT115(DE)3. Transferring the Cas9-RNAi RNPs into mammalian cells achieves multidimensional genome manipulation, e.g., simultaneously knock out and knock down the target genes. Moreover, by introduction of a shRNA against the gene of human DNA ligase 4 (LIG4), significantly improved homology-directed repair was attained. Together, we develop a simple-to-use CRISPR RNP tool that has great potentials in precise genome editing, gene function analysis and gene therapy.
A bipartite, low-affinity roadblock domain-containing GAP complex regulates bacterial front-rear polarity
Authors: Szadkowski Dobromir , Carreira Luís António Menezes , Søgaard-Andersen Lotte 
Published: March 2022

AbstractThe Ras-like GTPase MglA is a key regulator of front-rear polarity in rod-shaped Myxococcus xanthus cells. MglA-GTP localizes to the leading cell pole and stimulates assembly of the two motility machineries. MglA-GTP localization is spatially constrained by its cognate GEF, the RomR/RomX complex, and GAP, the MglB Roadblock-domain protein. RomR/RomX and MglB localize similarly with low and high concentrations at the leading and lagging poles, respectively. Yet, GEF activity dominates at the leading and GAP activity at the lagging pole by unknown mechanisms. Here, we identify RomY as a co-GAP that stimulates MglB GAP activity. The MglB/RomY interaction is low affinity, restricting complex formation to the lagging pole with the high MglB concentration. Our data support a model wherein RomY, by forming a low-affinity complex with MglB, ensures that MglB GAP activity is spatially precisely confined to the lagging pole, thereby constraining MglA-GTP to the leading pole establishing front-rear polarity.