Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity

The Application of a Hypothesis-driven Strategy to the Sensitive Detection and Location of Acetylated Lysine Residues

The application of a hypothesis-driven method for the sensitive determination of lysine acetylation sites on enzymatically digested proteins is described. Comparative sensitivity tests were carried out using serial dilution of an acetylated bovine serum albumin (AcBSA) digest to assess the performance of a multiple reaction monitoring (MRM)–based approach as compared to a more conventional precursor scanning (PS) method. Both methods were capable of selectively detecting an acetylated peptide at the low femtomole level when spiked into a background of 500 fmol six-protein tryptic digest. The MRM approach was roughly tenfold more sensitive than precursor scanning with one acetylated peptide detected and sequenced at the level of 2 fmol on-column. The technique was subsequently applied to a gel-derived sample of cytokeratin-8 (CK8) shown to contain acetylated lysine residues by Western blot analysis. The strategy applied herein, termed MRM-initiated detection and sequencing (MIDAS), resulted in the facile identification of novel sites of acetylation on this protein

Really Underage Drinkers: Alcohol Use Among Elementary Students

Despite the current societal concern with underage drinking, little attention has been paid to alcohol use within the preadolescent population. This article presents the proceedings of a symposium held at the 2003 Research Society on Alcoholism meeting in Fort Lauderdale, Florida, that was organized and chaired by John E. Donovan. The intent of the symposium was to kick start research on alcohol use among elementary school children by reviewing what is known regarding drinking in childhood. Presentations included (1) The Epidemiology of Children's Alcohol Use, by John E. Donovan; (2) The Validity of Children's Self-Reports of Alcohol Use, by Sharon L. Leech; (3) Predicting Onset of Drinking From Behavior at Three Years of Age: Influence of Early Child Expectancies and Parental Alcohol Involvement Upon Early First Use, by Robert A. Zucker; and (4) Parent, Peer, and Child Risk Factors for Alcohol Use in Two Cohorts of Elementary School Children, by Carol J. Loveland-Cherry. Presentations indicated the need for better nationwide surveillance of children's experience with alcohol; suggested that children's reports of their use of alcohol tend to be reliable and valid; supported children's alcohol use schemas and parental drinking and alcoholism at child age three as independent predictors of early onset drinking; and showed that onset of drinking before fourth or fifth grade, peer pressure, and parental norms and monitoring predict elementary student alcohol use and misuse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65944/1/01.ALC.0000113922.77569.4E.pd

Personal Finance: An Interdisciplinary Profession

This commentary recommends that financial counseling and planning research, education, and practice be framed as an interdisciplinary profession called personal finance. Authors summarize the history of the profession and key theories providing the conceptual foundation. In order for the emerging profession of personal finance to achieve significant visibility and gain maturity, professionals must reach consensus on definining collective scholarship. Readers are encouraged to engage in the dialogue and comment on the call to action by contacting the lead author

Integrated molecular approaches for fermented food microbiome research

peer-reviewedMolecular technologies, including high-throughput sequencing, have expanded our perception of the microbial world. Unprecedented insights into the composition and function of microbial communities have generated large interest, with numerous landmark studies published in recent years relating the important roles of microbiomes and the environment—especially diet and nutrition—in human, animal, and global health. As such, food microbiomes represent an important cross-over between the environment and host. This is especially true of fermented food microbiomes, which actively introduce microbial metabolites and, to a lesser extent, live microbes into the human gut. Here, we discuss the history of fermented foods, and examine how molecular approaches have advanced research of these fermented foods over the past decade. We highlight how various molecular approaches have helped us to understand the ways in which microbes shape the qualities of these products, and we summarize the impacts of consuming fermented foods on the gut. Finally, we explore how advances in bioinformatics could be leveraged to enhance our understanding of fermented foods. This review highlights how integrated molecular approaches are changing our understanding of the microbial communities associated with food fermentation, the creation of unique food products, and their influences on the human microbiome and health.Horizon 202

Mask wearing in community settings reduces SARS-CoV-2 transmission

The effectiveness of mask wearing at controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been unclear. While masks are known to substantially reduce disease transmission in healthcare settings [D. K. Chu et al., Lancet 395, 1973–1987 (2020); J. Howard et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2014564118 (2021); Y. Cheng et al., Science eabg6296 (2021)], studies in community settings report inconsistent results [H. M. Ollila et al., medRxiv (2020); J. Brainard et al., Eurosurveillance 25, 2000725 (2020); T. Jefferson et al., Cochrane Database Syst. Rev. 11, CD006207 (2020)]. Most such studies focus on how masks impact transmission, by analyzing how effective government mask mandates are. However, we find that widespread voluntary mask wearing, and other data limitations, make mandate effectiveness a poor proxy for mask-wearing effectiveness. We directly analyze the effect of mask wearing on SARS-CoV-2 transmission, drawing on several datasets covering 92 regions on six continents, including the largest survey of wearing behavior ([Formula: see text] 20 million) [F. Kreuter et al., https://gisumd.github.io/COVID-19-API-Documentation (2020)]. Using a Bayesian hierarchical model, we estimate the effect of mask wearing on transmission, by linking reported wearing levels to reported cases in each region, while adjusting for mobility and nonpharmaceutical interventions (NPIs), such as bans on large gatherings. Our estimates imply that the mean observed level of mask wearing corresponds to a 19% decrease in the reproduction number R. We also assess the robustness of our results in 60 tests spanning 20 sensitivity analyses. In light of these results, policy makers can effectively reduce transmission by intervening to increase mask wearing

Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome

peer-reviewedLactic acid bacteria (LAB) are fundamental in the production of fermented foods and several strains are regarded as probiotics. Large quantities of live LAB are consumed within fermented foods, but it is not yet known to what extent the LAB we ingest become members of the gut microbiome. By analysis of 9445 metagenomes from human samples, we demonstrate that the prevalence and abundance of LAB species in stool samples is generally low and linked to age, lifestyle, and geography, with Streptococcus thermophilus and Lactococcus lactis being most prevalent. Moreover, we identify genome-based differences between food and gut microbes by considering 666 metagenome-assembled genomes (MAGs) newly reconstructed from fermented food microbiomes along with 154,723 human MAGs and 193,078 reference genomes. Our large-scale genome-wide analysis demonstrates that closely related LAB strains occur in both food and gut environments and provides unprecedented evidence that fermented foods can be indeed regarded as a possible source of LAB for the gut microbiome

The Updated Zwicky Catalog (UZC)

The Zwicky Catalog of galaxies (ZC), with m_Zw<=15.5mag, has been the basis for the Center for Astrophysics (CfA) redshift surveys. To date, analyses of the ZC and redshift surveys based on it have relied on heterogeneous sets of galaxy coordinates and redshifts. Here we correct some of the inadequacies of previous catalogs by providing: (1) coordinates with <~2 arcsec errors for all of the Nuzc catalog galaxies, (2) homogeneously estimated redshifts for the majority (98%) of the data taken at the CfA (14,632 spectra), and (3) an estimate of the remaining "blunder" rate for both the CfA redshifts and for those compiled from the literature. For the reanalyzed CfA data we include a calibrated, uniformly determined error and an indication of the presence of emission lines in each spectrum. We provide redshifts for 7,257 galaxies in the CfA2 redshift survey not previously published; for another 5,625 CfA redshifts we list the remeasured or uniformly re-reduced value. Among our new measurements, Nmul are members of UZC "multiplets" associated with the original Zwicky catalog position in the coordinate range where the catalog is 98% complete. These multiplets provide new candidates for examination of tidal interactions among galaxies. All of the new redshifts correspond to UZC galaxies with properties recorded in the CfA redshift compilation known as ZCAT. About 1,000 of our new measurements were motivated either by inadequate signal-to-noise in the original spectrum or by an ambiguous identification of the galaxy associated with a ZCAT redshift. The redshift catalog we include here is ~96% complete to m_Zw<=15.5, and ~98% complete (12,925 galaxies out of a total of 13,150) for the RA(1950) ranges [20h--4h] and [8h--17h] and DEC(1950) range [-2.5d--50d]. (abridged)Comment: 34 pp, 7 figs, PASP 1999, 111, 43

Manipulation of autophagy in phagocytes facilitates <i>Staphylococcus aureus</i> bloodstream infection

The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of Staphylococcus aureus in the host. To date, the majority of work on S. aureus-phagocyte interactions has focused on neutrophils and, to a lesser extent, macrophages, yet we understand little about the role played by dendritic cells (DCs) in the direct killing of this bacterium. Using bone marrow-derived DCs (BMDCs), we demonstrate for the first time that DCs can effectively kill S. aureus but that certain strains of S. aureus have the capacity to evade DC (and macrophage) killing by manipulation of autophagic pathways. Strains with high levels of Agr activity were capable of causing autophagosome accumulation, were not killed by BMDCs, and subsequently escaped from the phagocyte, exerting significant cytotoxic effects. Conversely, strains that exhibited low levels of Agr activity failed to accumulate autophagosomes and were killed by BMDCs. Inhibition of the autophagic pathway by treatment with 3-methyladenine restored the bactericidal effects of BMDCs. Using an in vivo model of systemic infection, we demonstrated that the ability of S. aureus strains to evade phagocytic cell killing and to survive temporarily within phagocytes correlated with persistence in the periphery and that this effect is critically Agr dependent. Taken together, our data suggest that strains of S. aureus exhibiting high levels of Agr activity are capable of blocking autophagic flux, leading to the accumulation of autophagosomes. Within these autophagosomes, the bacteria are protected from phagocytic killing, thus providing an intracellular survival niche within professional phagocytes, which ultimately facilitates dissemination