Bacterial community profiles in low microbial abundance sponges

It has long been recognized that sponges differ in the abundance of associated microorganisms, and they are therefore termed either 'low microbial abundance' (LMA) or 'high microbial abundance' (HMA) sponges. Many previous studies concentrated on the dense microbial communities in HMA sponges, whereas little is known about microorganisms in LMA sponges. Here, two LMA sponges from the Red Sea, two from the Caribbean and one from the South Pacific were investigated. With up to only five bacterial phyla per sponge, all LMA sponges showed lower phylum-level diversity than typical HMA sponges. Interestingly, each LMA sponge was dominated by a large clade within either Cyanobacteria or different classes of Proteobacteria. The overall similarity of bacterial communities among LMA sponges determined by operational taxonomic unit and UniFrac analysis was low. Also the number of sponge-specific clusters, which indicate bacteria specifically associated with sponges and which are numerous in HMA sponges, was low. A biogeographical or host-dependent distribution pattern was not observed. In conclusion, bacterial community profiles of LMA sponges are clearly different from profiles of HMA sponges and, remarkably, each LMA sponge seems to harbour its own unique bacterial communit

A social inference model of idealization and devaluation

People often form polarized beliefs, imbuing objects (e.g., themselves or others) with unambiguously positive or negative qualities. In clinical settings, this is referred to as dichotomous thinking or "splitting" and is a feature of several psychiatric disorders. Here, we introduce a Bayesian model of splitting that parameterizes a tendency to rigidly categorize objects as either entirely "Bad" or "Good," rather than to flexibly learn dispositions along a continuous scale. Distinct from the previous descriptive theories, the model makes quantitative predictions about how dichotomous beliefs emerge and are updated in light of new information. Specifically, the model addresses how splitting is context-dependent, yet exhibits stability across time. A key model feature is that phases of devaluation and/or idealization are consolidated by rationally attributing counter-evidence to external factors. For example, when another person is idealized, their less-than-perfect behavior is attributed to unfavorable external circumstances. However, sufficient counter-evidence can trigger switches of polarity, producing bistable dynamics. We show that the model can be fitted to empirical data, to measure individual susceptibility to relational instability. For example, we find that a latent categorical belief that others are "Good" accounts for less changeable, and more certain, character impressions of benevolent as opposed to malevolent others among healthy participants. By comparison, character impressions made by participants with borderline personality disorder reveal significantly higher and more symmetric splitting. The generative framework proposed invites applications for modeling oscillatory relational and affective dynamics in psychotherapeutic contexts. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease

US States’ Childhood Obesity Surveillance Practices and Recommendations for Improving Them, 2014–2015

Introduction: Routine collection, analysis, and reporting of data on child height, weight, and body mass index (BMI), particularly at the state and local levels, are needed to monitor the childhood obesity epidemic, plan intervention strategies, and evaluate the impact of interventions. Child BMI surveillance systems operated by the US government do not provide state or local data on children across a range of ages. The objective of this study was to describe the extent to which state governments conduct child BMI surveillance. Methods: From August through December 2014, we conducted a structured telephone survey with state government administrators to learn about state surveillance of child BMI. We also searched websites of state health and education agencies for information about state surveillance. Results: State agency administrators in 48 states and Washington, DC, completed telephone interviews (96% response rate). Based on our interviews and Internet research, we determined that 14 states collect child BMI data in a manner consistent with standard definitions of public health surveillance. Conclusion: The absence of child BMI surveillance systems in most states limits the ability of public health practitioners and policymakers to develop and evaluate responses to the childhood obesity epidemic. Greater investment in surveillance is needed to identify the most effective and cost-effective childhood obesity interventions

Engineering Genetically-Encoded Mineralization and Magnetism via Directed Evolution

Genetically encoding the synthesis of functional nanomaterials such as magnetic nanoparticles enables sensitive and non-invasive biological sensing and control. Via directed evolution of the natural iron-sequestering ferritin protein, we discovered key mutations that lead to significantly enhanced cellular magnetism, resulting in increased physical attraction of ferritin-expressing cells to magnets and increased contrast for cellular magnetic resonance imaging (MRI). The magnetic mutants further demonstrate increased iron biomineralization measured by a novel fluorescent genetic sensor for intracellular free iron. In addition, we engineered Escherichia coli cells with multiple genomic knockouts to increase cellular accumulation of various metals. Lastly to explore further protein candidates for biomagnetism, we characterized members of the DUF892 family using the iron sensor and magnetic columns, confirming their intracellular iron sequestration that results in increased cellular magnetization

Secondary injury and inflammation after intracerebral haemorrhage: a systematic review and meta-analysis of molecular markers in patient brain tissue

BACKGROUND: Inflammatory responses to intracerebral haemorrhage (ICH) are potential therapeutic targets. We aimed to quantify molecular markers of inflammation in human brain tissue after ICH compared with controls using meta-analysis. METHODS: We searched OVID MEDLINE (1946–) and Embase (1974–) in June 2020 for studies that reported any measure of a molecular marker of inflammation in brain tissue from five or more adults after ICH. We assessed risk of bias using a modified Newcastle-Ottawa Scale (mNOS; mNOS score 0–9; 9 indicates low bias), extracted aggregate data, and used random effects meta-analysis to pool associations of molecules where more than two independent case–control studies reported the same outcome and Gene Ontology enrichment analysis to identify over-represented biological processes in pooled sets of differentially expressed molecules (International Prospective Register of Systematic Reviews ID: CRD42018110204). RESULTS: Of 7501 studies identified, 44 were included: 6 were case series and 38 were case–control studies (median mNOS score 4, IQR 3–5). We extracted data from 21 491 analyses of 20 951 molecules reported by 38 case–control studies. Only one molecule (interleukin-1β protein) was quantified in three case–control studies (127 ICH cases vs 41 ICH-free controls), which found increased abundance of interleukin-1β protein after ICH (corrected standardised mean difference 1.74, 95% CI 0.28 to 3.21, p=0.036, I(2)=46%). Processes associated with interleukin-1β signalling were enriched in sets of molecules that were more abundant after ICH. CONCLUSION: Interleukin-1β abundance is increased after ICH, but analyses of other inflammatory molecules after ICH lack replication. Interleukin-1β pathway modulators may optimise inflammatory responses to ICH and merit testing in clinical trials

Multilevel Monte Carlo for exponential Lévy models

We apply the multilevel Monte Carlo method for option pricing problems using exponential Lévy models with a uniform timestep discretisation. For lookback and barrier options, we derive estimates of the convergence rate of the error introduced by the discrete monitoring of the running supremum of a broad class of Lévy processes. We then use these to obtain upper bounds on the multilevel Monte Carlo variance convergence rate for the Variance Gamma, NIG and a-stable processes. We also provide analysis of a trapezoidal approximation for Asian options. Our method is illustrated by numerical experiments

The Fermi GBM Gamma-Ray Burst Spectral Catalog: Four Years Of Data

In this catalog we present the updated set of spectral analyses of GRBs detected by the Fermi Gamma-Ray Burst Monitor (GBM) during its first four years of operation. It contains two types of spectra, time-integrated spectral fits and spectral fits at the brightest time bin, from 943 triggered GRBs. Four different spectral models were fitted to the data, resulting in a compendium of more than 7500 spectra. The analysis was performed similarly, but not identically to Goldstein et al. 2012. All 487 GRBs from the first two years have been re-fitted using the same methodology as that of the 456 GRBs in years three and four. We describe, in detail, our procedure and criteria for the analysis, and present the results in the form of parameter distributions both for the observer-frame and rest-frame quantities. The data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center (HEASARC).Comment: Accepted for publication in ApJ

Symbiotic Nitrogen Fixation and the Challenges to Its Extension to Nonlegumes

Access to fixed or available forms of nitrogen limits the productivity of crop plants and thus food production. Nitrogenous fertilizer production currently represents a significant expense for the efficient growth of various crops in the developed world. There are significant potential gains to be had from reducing dependence on nitrogenous fertilizers in agriculture in the developed world and in developing countries, and there is significant interest in research on biological nitrogen fixation and prospects for increasing its importance in an agricultural setting. Biological nitrogen fixation is the conversion of atmospheric N2 to NH3, a form that can be used by plants. However, the process is restricted to bacteria and archaea and does not occur in eukaryotes. Symbiotic nitrogen fixation is part of a mutualistic relationship in which plants provide a niche and fixed carbon to bacteria in exchange for fixed nitrogen. This process is restricted mainly to legumes in agricultural systems, and there is considerable interest in exploring whether similar symbioses can be developed in nonlegumes, which produce the bulk of human food. We are at a juncture at which the fundamental understanding of biological nitrogen fixation has matured to a level that we can think about engineering symbiotic relationships using synthetic biology approaches. This minireview highlights the fundamental advances in our understanding of biological nitrogen fixation in the context of a blueprint for expanding symbiotic nitrogen fixation to a greater diversity of crop plants through synthetic biology.Biotechnology and Biological Sciences Research Council (Great Britain) (Grants BB/L011484/1 and BB/L011476/1)National Science Foundation (U.S.) (Grant 1331098

Gene flow in environmental Legionella pneumophila leads to genetic and pathogenic heterogeneity within a Legionnaires' disease outbreak

BACKGROUND: Legionnaires’ disease is a severe form of pneumonia caused by the environmental bacterium Legionella pneumophila. Outbreaks commonly affect people with known risk factors, but the genetic and pathogenic complexity of L. pneumophila within an outbreak is not well understood. Here, we investigate the etiology of the major Legionnaires’ disease outbreak that occurred in Edinburgh, UK, in 2012, by examining the evolutionary history, genome content, and virulence of L. pneumophila clinical isolates. RESULTS: Our high resolution genomic approach reveals that the outbreak was caused by multiple genetic subtypes of L. pneumophila, the majority of which had diversified from a single progenitor through mutation, recombination, and horizontal gene transfer within an environmental reservoir prior to release. In addition, we discover that some patients were infected with multiple L. pneumophila subtypes, a finding which can affect the certainty of source attribution. Importantly, variation in the complement of type IV secretion systems encoded by different genetic subtypes correlates with virulence in a Galleria mellonella model of infection, revealing variation in pathogenic potential among the outbreak source population of L. pneumophila. CONCLUSIONS: Taken together, our study indicates previously cryptic levels of pathogen heterogeneity within a Legionnaires’ disease outbreak, a discovery that impacts on source attribution for future outbreak investigations. Furthermore, our data suggest that in addition to host immune status, pathogen diversity may be an important influence on the clinical outcome of individual outbreak infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0504-1) contains supplementary material, which is available to authorized users