The Response of Marine Synechococcus to a Landscape of Environmental Stressors: a Proteomic Exploration

In the field of marine microbial ecology, many questions remain unanswered with regards to the physiological trade-offs made by phytoplankton to maximize growth (e.g., nutrient acquisition) and minimize loss (e.g., predation defenses). These tradeoffs, which occur at the cellular level, have wide reaching impacts on food web dynamics and global biogeochemical cycles. In the first chapter, we explored the use of a non-canonical amino acid (NCAA) technique, bioorthogonal non-canonical amino-acid tagging (BONCAT), in phytoplankton model systems. This technique has potential to work well in natural systems by enabling isolation of only newly synthesized proteins during an incubation period with the NCAA, reducing the complexity of natural proteomics and easing the elucidation of patterns. However, in testing BONCAT across several groups of cultured phytoplankton, we discovered that the NCAA molecule induced a stress response in the globally ubiquitous marine picocyanobacteria, Synechococcus sp. Therefore, in addition to confirming the uptake of modified amino acids by phytoplankton, chapter one investigated the implications of this stress response and limitations when using this technique to study marine microbial communities. In chapter two, we addressed our initial question by exploring tradeoffs at the protein level in a simplified culture system. This approach revealed insights into metabolic tradeoffs in response to predation pressure and nutrient stress. These insights into how phytoplankton negotiate these physiological tradeoffs at the protein level could ultimately allow for targeted proteomic studies in natural systems

Data from: Diet breadth and exploitation of exotic plants shift the core microbiome of Cephaloleia, a group of tropical herbivorous beetles

The beetle genus Cephaloleia has evolved in association with tropical ginger plants and for many species their specific host plant associations are known. Here we show that the core microbiome of six closely related Costa Rican Cephaloleia species comprises only eight bacterial groups, including members of the Acinetobacter, Enterobacteriacea, Pseudomonas, Lactococcus, and Comamonas. The Acinetobacter and Enterobacteriacea together accounted for 35% of the total average 16S rRNA ribotypes recovered from all specimens. Further, microbiome diversity and community structure was significantly linked to beetle diet breadth, between those foraging on less than two plant types (specialists) versus over nine plant types (generalists). Moraxellaceae, Enterobacteriaceae, and Pseudomonadaceae were highly prevalent in specialist species, and also present in eggs, while Rickettsiaceae associated exclusively with generalist beetles. Bacteria isolated from Cephaloleia digestive systems had distinct capabilities and suggested a possible beneficial role in both digestion of plant-based compounds, including xylose, mannitol, and pectin, and possible detoxification, via lipases. Cephaloleia species are currently expanding their diets to include exotic invasive plants, yet it is unknown whether their microbial community plays a role in this transition. In this study, colonization of invasive plants was correlated with a dysbiosis of the microbiome, suggesting a possible relationship between gut bacteria and niche adaptation

Diet breadth and exploitation of exotic plants shift the core microbiome of Cephaloleia, a group of tropical herbivorous beetles

The beetle genus Cephaloleia has evolved in association with tropical ginger plants and for many species their specific host plant associations are known. Here we show that the core microbiome of six closely related Costa Rican Cephaloleia species comprises only eight bacterial groups, including members of the Acinetobacter, Enterobacteriacea, Pseudomonas, Lactococcus, and Comamonas. The Acinetobacter and Enterobacteriacea together accounted for 35% of the total average 16S rRNA ribotypes recovered from all specimens. Further, microbiome diversity and community structure was significantly linked to beetle diet breadth, between those foraging on less than two plant types (specialists) versus over nine plant types (generalists). Moraxellaceae, Enterobacteriaceae, and Pseudomonadaceae were highly prevalent in specialist species, and also present in eggs, while Rickettsiaceae associated exclusively with generalist beetles. Bacteria isolated from Cephaloleia digestive systems had distinct capabilities and suggested a possible beneficial role in both digestion of plant-based compounds, including xylose, mannitol, and pectin, and possible detoxification, via lipases. Cephaloleia species are currently expanding their diets to include exotic invasive plants, yet it is unknown whether their microbial community plays a role in this transition. In this study, colonization of invasive plants was correlated with a dysbiosis of the microbiome, suggesting a possible relationship between gut bacteria and niche adaptation

Comparative Effectiveness of Early Versus Conventional Timing of Dialysis Initiation in Advanced CKD

Background: Previous observational studies examining outcomes associated with the timing of dialysis therapy initiation in the United States have often been limited by lead time and survivor bias. Study Design: Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis therapy initiation in advanced chronic kidney disease (CKD). The analysis used inverse probability weighting to account for an individual's contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy (ie, dialysis therapy was initiated early or estimated glomerular filtration rate [eGFR] decreased to <10 mL/min/1.73 m(2)). Setting & Participants: Patients with CKD who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005, and at least 3 eGFRs in the range of 20-30 mL/min/1.73 m(2) measured at least 180 days apart. Predictors: Timing of dialysis therapy initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis therapy initiation 10 mL/min/1.73 m(2)) or later (eGFR <10 mL/min/1.73 m(2)) and was time-varying. Outcomes: Death from any cause occurring from the time that eGFR was equal to 20 mL/min/1.73 m(2) through September 15, 2009. Results: The study population consisted of 652 patients meeting inclusion criteria. Most (71.3%) of the study population did not initiate dialysis therapy during follow-up. Patients who did not initiate dialysis therapy (n = 465) were older, more likely to be white, and had more favorable laboratory profiles than those who started dialysis therapy. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to <10 mL/min/1.73 m(2). Many participants (n = 426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival difference for the early compared with later initiation strategy (OR, 0.85; 95% Cl, 0.65-1.11). Limitations: Interpolated eGFR, moderate sample size, and likely unmeasured confounders. Conclusions: In patients with advanced CKD, timing of dialysis therapy initiation was not associated with mortality when accounting for lead time bias and survivor bias. (C) 2014 by the National Kidney Foundation, In

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts

BackgroundPhthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.ObjectivesWe investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity.MethodsWe pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth.ResultsIn comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants.ConclusionsPhthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831

Happy heart syndrome: role of positive emotional stress in takotsubo syndrome

Aims Takotsubo syndrome (TTS) is typically provoked by negative stressors such as grief, anger, or fear leading to the popular term broken heart syndrome. However, the role of positive emotions triggering TTS remains unclear. The aim of the present study was to analyse the prevalence and characteristics of patients with TTS following pleasant events, which are distinct from the stressful or undesirable episodes commonly triggering TTS. Methods and results Takotsubo syndrome patients with preceding pleasant events were compared to those with negative emotional triggers from the International Takotsubo Registry. Of 1750 TTS patients, we identified a total of 485 with a definite emotional trigger. Of these, 4.1% (n = 20) presented with pleasant preceding events and 95.9% (n = 465) with unequivocal negative emotional events associated with TTS. Interestingly, clinical presentation of patients with happy heart syndrome was similar to those with the broken heart syndrome including symptoms such as chest pain [89.5% (17/19) vs. 90.2% (412/457), P = 1.0]. Similarly, electrocardiographic parameters, laboratory findings, and 1-year outcome did not differ. However, in a post hoc analysis, a disproportionate higher prevalence of midventricular involvement was noted in happy hearts compared with broken hearts (35.0 vs. 16.3%, P = 0.030). Conclusion Our data illustrate that TTS can be triggered by not only negative but also positive life events. While patient characteristics were similar between groups, the midventricular TTS type was more prevalent among the happy hearts than among the broken hearts. Presumably, despite their distinct nature, happy and sad life events may share similar final common emotional pathways, which can ultimately trigger TTS

A novel clinical score (InterTAK Diagnostic Score) to differentiate takotsubo syndrome from acute coronary syndrome: results from the International Takotsubo Registry

Aims Clinical presentation of takotsubo syndrome (TTS) mimics acute coronary syndrome (ACS) and does not allow differentiation. We aimed to develop a clinical score to estimate the probability of TTS and to distinguish TTS from ACS in the acute stage. Methods and results Patients with TTS were recruited from the International Takotsubo Registry (www.takotsubo-registry.com) and ACS patients from the leading hospital in Zurich. A multiple logistic regression for the presence of TTS was performed in a derivation cohort (TTS, n = 218; ACS, n = 436). The best model was selected and formed a score (InterTAK Diagnostic Score) with seven variables, and each was assigned a score value: female sex 25, emotional trigger 24, physical trigger 13, absence of ST-segment depression (except in lead aVR) 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve (AUC) for the resulting score was 0.971 [95% confidence interval (CI) 0.96-0.98] and using a cut-off value of 40 score points, sensitivity was 89% and specificity 91%. When patients with a score of >= 50 were diagnosed as TTS, nearly 95% of TTS patients were correctly diagnosed. When patients with a score <= 31 were diagnosed as ACS, similar to 95% of ACS patients were diagnosed correctly. The score was subsequently validated in an independent validation cohort (TTS, n = 173; ACS, n = 226), resulting in a score AUC of 0.901 (95% CI 0.87-0.93). Conclusion The InterTAK Diagnostic Score estimates the probability of the presence of TTS and is able to distinguish TTS from ACS with a high sensitivity and specificity

Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers

BACKGROUND:Although evidence suggests that larger body size in early life confers lifelong protection from developing breast cancer, few studies have investigated the relationship between body size and breast cancer risk among BRCA mutation carriers. Therefore, we conducted a prospective evaluation of body size and the risk of breast cancer among BRCA mutation carriers. METHODS:Current height and body mass index (BMI) at age 18 were determined from baseline questionnaires. Current BMI and weight change since age 18 were calculated from updated biennial follow-up questionnaires. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS:Among 3734 BRCA mutation carriers, there were 338 incident breast cancers over a mean follow-up of 5.5 years. There was no association between height, current BMI or weight change and breast cancer risk. Women with BMI at age 18 ≥22.1 kg/m2 had a decreased risk of developing post-menopausal breast cancer compared with women with a BMI at age 18 between 18.8 and 20.3 kg/m2 (HR 0.49; 95% CI 0.30-0.82; P = 0.006). BMI at age 18 was not associated with risk of pre-menopausal breast cancer. CONCLUSIONS:There was no observed association between height, current BMI and weight change and risk of breast cancer. The inverse relationship between greater BMI at age 18 and post-menopausal breast cancer further supports a role of early rather than current or adulthood exposures for BRCA-associated breast cancer development. Future studies with longer follow-up and additional measures of adiposity are necessary to confirm these findings