Social networks strongly predict the gut microbiota of wild mice

The mammalian gut teems with microbes, yet how hosts acquire these symbionts remains poorly understood. Research in primates suggests that microbes can be picked up via social contact, but the role of social interactions in non-group-living species remains underexplored. Here, we use a passive tracking system to collect high resolution spatiotemporal activity data from wild mice (Apodemus sylvaticus). Social network analysis revealed social association strength to be the strongest predictor of microbiota similarity among individuals, controlling for factors including spatial proximity and kinship, which had far smaller or nonsignificant effects. This social effect was limited to interactions involving males (male-male and male-female), implicating sex-dependent behaviours as driving processes. Social network position also predicted microbiota richness, with well-connected individuals having the most diverse microbiotas. Overall, these findings suggest social contact provides a key transmission pathway for gut symbionts even in relatively asocial mammals, that strongly shapes the adult gut microbiota. This work underlines the potential for individuals to pick up beneficial symbionts as well as pathogens from social interactions.Peer reviewe

The Lantern, 2014-2015

• The Retreat • Part of Eve\u27s Discussion • Buchanan • Hypotheticals • The Baby Hippo • Sertraline and Cheerios • Margins • Anatomy of Me • Orange • Ode to Mathematics • Garden Path • Periphery • 10n Power=Our Maybe Domains • Hillside • Baltimore//Analogues • Work is a Religion • At the Bridal Shower • November • Revisionist History • Cold Front • Lung (for D. Avitabile) • Tether • Hold Still • Reverb • An Almost English Major and His Daughter • Clocks • In the Kitchen on a Sunday Afternoon • Amy • Nine • Customary Thoughts • Showers • Te Encuentro • I Find You • Literary Analysis • The Diamond on My Face • Catherine • Hunsberger Woods, 11:42 on a School Night • Cabbage • After Class • For Chell • To Whom It May Concern • Contra • Shards • Smoke and Roses • Polaroid • Spring\u27s Debut • The Deadline • A Previous Life • Wet Canvas • Obsessions and Compulsions • For Xandra • The Seagulls of 17th Street • No Man\u27s Land • Summer Flowers • Float • Dana Reads • A Barcelona Moment • Business Meeting • Posted • Champagnehttps://digitalcommons.ursinus.edu/lantern/1181/thumbnail.jp

Density-dependent network structuring within and across wild animal systems

Theory predicts that high population density leads to more strongly connected spatial and social networks, but how local density drives individuals' positions within their networks is unclear. This gap reduces our ability to understand and predict density-dependent processes. Here we show that density drives greater network connectedness at the scale of individuals within wild animal populations. Across 36 datasets of spatial and social behaviour in >58,000 individual animals, spanning 30 species of fish, reptiles, birds, mammals and insects, 80% of systems exhibit strong positive relationships between local density and network centrality. However, >80% of relationships are nonlinear and 75% are shallower at higher values, indicating saturating trends that probably emerge as a result of demographic and behavioural processes that counteract density's effects. These are stronger and less saturating in spatial compared with social networks, as individuals become disproportionately spatially connected rather than socially connected at higher densities. Consequently, ecological processes that depend on spatial connections are probably more density dependent than those involving social interactions. These findings suggest fundamental scaling rules governing animal social dynamics, which could help to predict network structures in novel systems

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Inhibition of Nitrifiers and Methanotrophs from an Agricultural Humisol by Allylsulfide and Its Implications for Environmental Studies

ABSTRACTAllylsulfide, an inhibitor of ammonia monooxygenase, was tested to determine its ability to inhibit nitrification and methane oxidation in pure cultures, in agricultural humisol enrichment cultures, and in humisol slurries. We confirmed that allylsulfide is a differential inhibitor of cultures of nitrifiers and methanotrophs at concentrations of 1 and 200 μM, respectively, which result in 50% inhibition. However, although a nitrifying enrichment culture added to sterilized humisol was inhibited 50% by 4 μM allylsulfide, 500 μM allylsulfide was necessary for 50% inhibition of the endogenous nitrifying activity in nonsterile humisol. We concluded that native nitrifiers were protected, possibly by being in colonial aggregates or sheltered microenvironments.</jats:p

1534-P: Relationship between Metabolic Syndrome Score and Insulin Resistance

Metabolic syndrome (MS) identifies previously unrecognized individuals at risk for diabetes and cardiovascular disease. Although MS is defined as requiring ≥3 of 5 categorical factors, a continuous MS score (using race/ethnicity modified Z-scores) has been proposed to better predict outcomes and track changes with interventions. As insulin resistance (IR) may link the 5 MS factors and their risk to outcomes, we hypothesized that MS score may reflect IR and its change with different therapies. We therefore determined MS score and IR by steady-state plasma glucose (SSPG) during the Insulin Suppression Test in persons without diabetes at baseline (n=611) and before and after 3 interventions: weight loss (WL; n=29), pioglitazone (PIO; n=32), and atorvastatin (ATR; n=36). Baseline MS score correlated (r value) with SSPG (0.58), similar to the correlations of BMI with SSPG (0.54) and MS score (0.55). MS score and SSPG, respectively, correlated with HDL-C (-0.63 vs. -0.33), triglycerides (TG; 0.82 vs. 0.38), systolic BP (0.38 vs. 0.22), fasting glucose (0.46 vs. 0.38), and TG/HDL-C ratio (0.87 vs. 0.42); P&amp;lt;0.01 for all. After WL and PIO, SSPG and MS score decreased (P&amp;lt;0.05). In contrast, after ATR, SSPG increased (P&amp;lt;0.05), but MS score decreased (P&amp;lt;0.01). The change (Δ) in MS score did not correlate with ΔSSPG in any of the groups, but strongly correlated with ΔTG/HDL-C ratio: WL (r=0.94), PIO (r=0.92), and ATR (r=0.79). In conclusion, MS score correlates modestly with SSPG, but strongly with TG and TG/HDL-C ratio. Changes in MS score in response to IR-modifying therapies do not appear to reflect changes in IR but rather changes in TG. This may limit use of MS score to evaluate change in IR or disease risk. Disclosure F. Abbasi: None. P. Reaven: Advisory Panel; Self; Boston Heart Diagnostics. Research Support; Self; AstraZeneca, Novo Nordisk Inc. J. Knowles: None. Funding Doris Duke Charitable Foundation </jats:sec

1736-P: Insulin Resistance and Mitochondrial Dysfunction Mediated by Nat1 Deficiency

Insulin resistance (IR) is fundamental to the pathophysiology of type 2 diabetes (T2D) and a major risk factor for cardiovascular disease (CVD). Therapeutic options for IR are limited, reinforcing the need to understand IR pathways with an aim to develop IR-specific medications. We previously identified human N-acetyl transferase 2 (NAT2) as a novel insulin sensitivity gene. In vitro and in vivo studies demonstrated an association of mouse Nat1 (ortholog of human NAT2) deficiency with both IR and mitochondrial dysfunction. However, the underlying mechanism of how Nat1 deficiency causes IR and mitochondrial dysfunction is unknown. Using engineered ascorbate peroxidase-proximity labeling in cells followed by mass spectrometry-based proteomic analysis, we are mapping Nat1 endogenous targets and Nat1 interacting proteins. Verification of the interacting proteins and functional validation will be achieved by co-immunoprecipitation, siRNA knockdown, glucose uptake and lipolysis assays, and mitochondrial functional assays in mouse liver cells and adipocytes. We have also created a liver specific Nat1-deficient mouse model and will determine whether this is sufficient to cause whole body changes in insulin sensitivity. Collectively, these studies will shed light on mechanism of how the novel IR gene Nat1 participates in the pathophysiology of IR, which is a necessary step for the development of new treatments for T2D and CVD. Disclosure P. Sangwung: None. M. Fathzadeh: None. J. Knowles: None. Funding American Diabetes Association (1-19-JDF-108 to J.K.); U.S. Public Health Service; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK107437, R01DK106236, P30DK116074, 1R01DK116750 to J.K.) </jats:sec