Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium

<p>Abstract</p> <p>Background</p> <p>Complete and accurate genome annotation is crucial for comprehensive and systematic studies of biological systems. However, determining protein-coding genes for most new genomes is almost completely performed by inference using computational predictions with significant documented error rates (> 15%). Furthermore, gene prediction programs provide no information on biologically important post-translational processing events critical for protein function.</p> <p>Results</p> <p>We experimentally annotated the bacterial pathogen <it>Salmonella </it>Typhimurium 14028, using "shotgun" proteomics to accurately uncover the translational landscape and post-translational features. The data provide protein-level experimental validation for approximately half of the predicted protein-coding genes in <it>Salmonella </it>and suggest revisions to several genes that appear to have incorrectly assigned translational start sites, including a potential novel alternate start codon. Additionally, we uncovered 12 non-annotated genes missed by gene prediction programs, as well as evidence suggesting a role for one of these novel ORFs in <it>Salmonella </it>pathogenesis. We also characterized post-translational features in the <it>Salmonella </it>genome, including chemical modifications and proteolytic cleavages. We find that bacteria have a much larger and more complex repertoire of chemical modifications than previously thought including several novel modifications. Our <it>in vivo </it>proteolysis data identified more than 130 signal peptide and N-terminal methionine cleavage events critical for protein function.</p> <p>Conclusion</p> <p>This work highlights several ways in which application of proteomics data can improve the quality of genome annotations to facilitate novel biological insights and provides a comprehensive proteome map of <it>Salmonella </it>as a resource for systems analysis.</p

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon

Impacts of Anisotropic Porosity on Heat Transfer and Off-Gassing during Biomass Pyrolysis

The pore structure of biogenic materials imbues the ability to deliver water and nutrients through a plant from root to leaf. This anisotropic pore granularity can also play a significant role in processes such as biomass pyrolysis that are used to convert these materials into useful products like heat, fuel, and chemicals. Evolutions in modeling of biomass pyrolysis as well as imaging of pore structures allow for further insights into the concerted physics of phase change-induced off-gassing, heat transfer, and chemical reactions. In this work, we report a biomass single particle model which incorporates these physics to explore the impact of implementing anisotropic permeability and diffusivity on the conversion time and yields predicted for pyrolysis of oak and pine particles. Simulation results showed that anisotropic permeability impacts predicted conversion time more than 2 times when the Biot number is above 0.1 and pyrolysis numbers (Py1, Py2) are less than 20. Pore structure significantly impacts predicted pyrolytic conversion time (>8 times) when the Biot number is above 1 and the pyrolysis number is below 1, i.e., the “conduction controlled” regime. Therefore, these nondimensional numbers reflect that when internal heat conduction limits pyrolysis performance, internal pyrolysis off-gassing further retards effective heat transfer rates as a closely coupled phenomenon. Overall, this study highlights physically meaningful opportunities to improve particle-scale pyrolysis modeling and experimental validation relevant to a variety of feedstock identities and preparations, guiding the future design of pyrolyzers for efficient biomass conversion.This article is published as Pecha, M. Brennan, Nicholas E. Thornburg, Chad A. Peterson, Meagan F. Crowley, Xi Gao, Liqiang Lu, Gavin Wiggins, Robert C. Brown, and Peter N. Ciesielski. "Impacts of Anisotropic Porosity on Heat Transfer and Off-Gassing during Biomass Pyrolysis." Energy & Fuels (2021). DOI: 10.1021/acs.energyfuels.1c02679. Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted

Meningococcal serogroups and surveillance: a systematic review and survey

Background: Meningococcal disease continues to be a global public health concern due to its epidemic potential, severity, and sequelae. The global epidemiological data on circulating meningococcal serogroups have never been reviewed concurrently with the laboratory capacity for meningococcal surveillance at the national level. We, therefore, aimed to conduct a country-level review of meningococcal surveillance, serogroup distribution, and vaccine use. Methods: We conducted a systematic literature review across six databases to identify studies (published January 1, 2010 to October 16, 2017) and grey literature reporting meningococcal serogroup data for the years 2010-2016. We performed independent random effects meta-analyses for serogroups A, B, C, W, X, Y, and other. We developed and circulated a questionnaire-based survey to surveillance focal points in countries (N = 95) with known regional bacterial meningitis surveillance programs to assess their surveillance capacity and summarized using descriptive methods. Results: We included 173 studies from 59 countries in the final analysis. The distribution of meningococcal serogroups differed markedly between countries and regions. Meningococcal serogroups C and W accounted for substantial proportions of meningococcal disease in most of Africa and Latin America. Serogroup B was the predominant cause of meningococcal disease in many locations in Europe, the Americas, and the Western Pacific. Serogroup Y also caused many cases of meningococcal disease in these regions, particularly in Nordic countries. Survey responses were received from 51 countries. All countries reported the ability to confirm the pathogen in-country, while approximately 30% either relied on reference laboratories for serogrouping (N = 10) or did not serogroup specimens (N = 5). Approximately half of countries did not utilize active laboratory-based surveillance system (N = 22). Nationwide use of a meningococcal vaccine varied, but most countries (N = 36) utilized a meningococcal vaccine at least for certain high-risk population groups, in private care, or during outbreaks. Conclusions: Due to the large geographical variations in circulating meningococcal serogroups, each country should continue to be monitored for changes in major disease-causing serogroups in order to inform vaccine and control policies. Similarly, laboratory capacity should be appropriately scaled up to more accurately understand local epidemiology and disease burden, as well as the impact of vaccination programs.Funding: This study was funded by Sanofi Pasteur. MHK and AM are employees of Sanofi Pasteur and had a role in study design, data interpretation, and preparation of the manuscript. YL is supported by a scholarship from the China Scholarship Council. l had no roThe China Scholarship Councile in study design, data interpretation, or preparation of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.S

Pulse oximetry training landscape for healthcare workers in low- and middle-income countries: A scoping review

Background Pulse oximetry has been used in medical care for decades. Its use quickly became standard of care in high resource settings, with delayed wide-spread availability and use in lower resource settings. Pulse oximetry training initiatives have been ongoing for years, but a map of the literature describing such initiatives among health care workers in low- and middle-income countries (LMICs) has not previously been conducted. Additionally, the coronavirus disease 2019 (COVID-19) pandemic further highlighted the inequitable distribution of pulse oximetry use and training. We aimed to characterise the landscape of pulse oximetry training for health care workers in LMICs prior to the COVID-19 pandemic as described in the literature. Methods We systematically searched six databases to identify studies reporting pulse oximetry training among health care workers, broadly defined, in LMICs prior to the COVID-19 pandemic. Two reviewers independently assessed titles and abstracts and relevant full texts for eligibility. Data were charted by one author and reviewed for accuracy by a second. We synthesised the results using a narrative synthesis. Results A total of 7423 studies were identified and 182 screened in full. A total of 55 training initiatives in 42 countries met inclusion criteria, as described in 66 studies since some included studies reported on different aspects of the same training initiative. Five overarching reasons for conducting pulse oximetry train?ing were identified: 1) anaesthesia and perioperative care, 2) respiratory support programme expansion, 3) perinatal assessment and monitoring, 4) assessment and monitoring of children and 5) assessment and monitoring of adults. Educational programmes varied in their purpose with respect to the types of patients being targeted, the health care workers being instructed, and the depth of pulse oximetry specific training. Conclusions Pulse oximetry training initiatives have been ongoing for decades for a variety of purposes, utilising a multitude of approaches to equip health care workers with tools to improve patient care. It is important that these initiatives continue as pulse oximetry availability and knowledge gaps remain. Neither pulse oximetry provision nor training alone is enough to bolster patient care, but sustainable solutions for both must be considered to meet the needs of both health care workers and patients.</p

Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.

The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota. Antibiotic treatment also facilitated rotavirus replication in type I and type III interferon (IFN) receptor-deficient mice, revealing IFN-independent proviral effects. Expression of interleukin-22 (IL-22) was strongly diminished in the intestine of antibiotic-treated mice. Treatment with exogenous IL-22 blocked rotavirus replication in microbiota-depleted wild-type and Stat1-/- mice, demonstrating that the antiviral effect of IL-22 in animals with altered microbiome is not dependent on IFN signaling. In antibiotic-treated animals, IL-22-induced a specific set of genes including Fut2, encoding fucosyl-transferase 2 that participates in the biosynthesis of fucosylated glycans which can mediate rotavirus binding. Interestingly, IL-22 also blocked rotavirus replication in antibiotic-treated Fut2-/- mice. Furthermore, IL-22 inhibited rotavirus replication in antibiotic-treated mice lacking key molecules of the necroptosis or pyroptosis pathways of programmed cell death. Taken together, our results demonstrate that IL-22 determines rotavirus susceptibility of antibiotic-treated mice, yet the IL-22-induced effector molecules conferring rotavirus resistance remain elusive