Bulletin No. 201 - Economic Insects in Some Streams of Northern Utah

The food of trout in our mountain streams is mainly insects. It is, in part, land insects that fall on the water and are taken as they float upon its surface, but in a much larger part it is insects that grow up in the water and are taken in their immature stages. These are the constant and dependable food-supply. They have been little studied hitherto. This bulletin is a report of a preliminary examination of some Utah streams, made for the purpose of discovering what forms of life are present in the streams and in what relative abundance. Some are beneficial and some injurious to trout, being competitors with them for food

Exploring Beta-Lactones as an Unexpected Link Between Hydrocarbon and Natural Product Biosynthesis in Bacteria

University of Minnesota Ph.D. dissertation. May 2017. Major: Biochemistry, Molecular Bio, and Biophysics. Advisor: Lawrence Wackett. 1 computer file (PDF); xi, 102 pages.Recent decades have seen a great interest in using biological systems as sources for the diverse chemicals used in modern society. The production of long-chain olefins (alkenes) from two fatty acids by diverse bacterial species has been well reported in literature and patented for the production of hydrocarbons. A four-gene cluster, oleABCD, encodes the enzymes responsible for this conversion; however, only two of the four enzymatic steps had been elucidated previously. Here, the third enzyme of the pathway, OleC, was characterized and found to convert beta-hydroxy acids to beta-lactones in an ATP-dependent reaction. beta-Lactone-containing natural products show great potential in clinical settings and are known for their potent inhibition of proteases and esterases. OleC is the first beta-lactone synthetase ever characterized, and sequence analysis suggests that the biosynthesis of other beta-lactone natural products is carried out by OleC homologues. The final enzymatic step of olefin biosynthesis was found to be the decarboxylation of the beta-lactone to an olefin by OleB. This enzymatic reaction was not known to exist in nature, making OleB the first known beta-lactone decarboxylase. OleB is frequently annotated as a haloalkane dehalogenase, but we find no dehalogenase activity, suggesting an incorrect annotation of OleB sequences. Mechanistic studies of OleB suggest a similar mechanism to haloalkane dehalogenases that relies on the same Asp-His-Asp catalytic triad and proceeds via an acyl-enzyme intermediate. Finally, the hydrophobic nature of the ole-pathway metabolites and the toxicity of the beta-lactone intermediate were hypothesized to require a direct transfer between the Ole enzymes. Accordingly, the four pathway enzymes, OleABCD, were recombinantly expressed in Escherichia coli, and OleBCD were found to form an enzyme complex. Immunoblots of OleC from the native Xanthomonas campestris on non-denaturing gels were found to migrate similarly to the recombinantly purified OleBCD complex and much slower than OleC by itself, suggesting formation of a complex in the native X. campestris host. Electron microscopy images showed distinct, circular assemblies of OleBCD between 24 and 40 nm in size, with an average size of 32 nm. The OleBCD complex functions to efficiently traffic the hydrophobic metabolites and sequester the toxic beta-lactone intermediate

N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study

Background Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. Objectives This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. Methods Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF. Results Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR− was 0.09 (95% CI: 0.05 to 0.13). Conclusions In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF

Cardiac Biomarkers and Risk of Atrial Fibrillation in Chronic Kidney Disease: The CRIC Study.

Background We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients. Methods and Results The study sample was 3053 participants with chronic kidney disease in the multicenter CRIC (Chronic Renal Insufficiency Cohort) study who were not identified as having AF at baseline. Cardiac biomarkers, measured at baseline, were NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin T, galectin-3, growth differentiation factor-15, and soluble ST-2. Incident AF ("AF event") was defined as a hospitalization for AF. During a median follow-up of 8 years, 279 (9%) participants developed a new AF event. In adjusted models, higher baseline log-transformed NT-proBNP (N-terminal pro-B-type natriuretic peptide) was associated with incident AF (adjusted hazard ratio [HR] per SD higher concentration: 2.11; 95% CI, 1.75, 2.55), as was log-high-sensitivity troponin T (HR 1.42; 95% CI, 1.20, 1.68). These associations showed a dose-response relationship in categorical analyses. Although log-soluble ST-2 was associated with AF risk in continuous models (HR per SD higher concentration 1.35; 95% CI, 1.16, 1.58), this association was not consistent in categorical analyses. Log-galectin-3 (HR 1.05; 95% CI, 0.91, 1.22) and log-growth differentiation factor-15 (HR 1.16; 95% CI, 0.96, 1.40) were not significantly associated with incident AF. Conclusions We found strong associations between higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity troponin T concentrations, and the risk of incident AF in a large cohort of participants with chronic kidney disease. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of AF in patients with chronic kidney disease

Prognostic Utility of a Modified HEART Score When Different Troponin Cut-points Are Used

BACKGROUND: Although the recommended cut-point for cardiac troponin (cTn) is the 99th percentile, many institutions use cut-points that are multiples higher than the 99th percentile for diagnosing acute myocardial infarction (AMI). Prior studies have shown that patients with a HEART score (HS) ≤ 3 and normal serial cTn values (modified HS) are at low risk for adverse events. This study aimed to evaluate the prognostic utility of the HS when various cTn cut-points are used. METHODS: This was a sub-study of TRAPID-AMI, a multicenter, international trial evaluating a rapid rule-out AMI study using high sensitivity cTnT (hs-cTnT). 1,282 patients were evaluated for AMI from 12 centers in Europe, United States of America, and Australia from 2011-2013. Blood samples of hs-cTnT were collected at presentation and 2 hours, and each patient had a HS calculated. The US Food and Drug Administration approved 99th percentile for hs-cTnT (19 ng/L) was used. RESULTS: There were 213 (17%) AMIs. Within 30 days, there were an additional 2 AMIs and 8 deaths. The adverse event rates at 30 days (death/AMI) for a HS ≤ 3 and non-elevated hs-cTnT over 2 hours using increasing hs-cTnT cut-points ranged from 0.6% to 5.1%. CONCLUSIONS: Using the recommended 99th percentile cut-point for hs-cTnT, the combination of a HS ≤ 3 with non-elevated hs-cTnT values over 2 hours identifies a low-risk cohort who can be considered for discharge from the emergency department without further testing. The prognostic utility of this strategy is greatly lessened as higher hs-cTnT cut-points are used

Intra-aortic balloon counterpulsation in US and non-US centres: results of the Benchmark® Registry

Aims To examine differences in patient characteristics and outcomes in 19 636 patients enrolled in the USA and 3027 patients enrolled in other countries undergoing intra-aortic balloon pump (IABP) counterpulsation. Methods and results Indications for IABP use; a larger percentage of US patients were identified as ‘early support and stabilization for angiography or angioplasty' (21.1% US vs 11.8% non-US), and ‘pre-operative support for high-risk CABG' (15.9% vs 6.6%). A smaller percentage of US patients vs non-US patients were identified as ‘weaning from cardiopulmonary bypass' (14.3% vs 28.2%), and ‘refractory ventricular failure' (6.2% vs 9.8%). One out of five patients in both groups was listed as ‘cardiogenic shock' (18.9% US vs 20.2% non-US). All cause, risk-adjusted, in-hospital mortality (20.1% vs 28.7%; P<0.001), and mortality with IABP in place (10.8% vs 18.0%; P<0.001) were lower at US vs non-US sites. In both US and non-US institutions, IABP associated complication rates, such as IABP-related mortality (0.05% vs 0.07%), major limb ischaemia (0.9% vs 0.8%), and severe bleeding (0.9% vs 0.8%), were low. Conclusions IABP counterpulsation is deployed at an earlier clinical stage in US patients. Mortality rates are higher for non-US patients, particularly for patients with non-surgery cardiac interventions, even after adjusting for risk factors. Complication rates were low. Physicians should therefore not be reluctant to use IABP in high-risk patients undergoing cardiac procedure

Active sites for ice nucleation differ depending on nucleation mode

The nucleation of ice crystals in clouds is poorly understood, despite being of critical importance for our planet's climate. Nucleation occurs largely at rare "active sites" present on airborne particles such as mineral dust, but the nucleation pathway is distinct under different meteorological conditions. These give rise to two key nucleation pathways where a particle is either immersed in a supercooled liquid water droplet (immersion freezing mode) or suspended in a supersaturated vapor (deposition mode). However, it is unclear if the same active sites are responsible for nucleation in these two modes. Here, we directly compare the sites that are active in these two modes by performing immersion freezing and deposition experiments on the same thin sections of two atmospherically important minerals (feldspar and quartz). For both substrates, we confirm that nucleation is dominated by a limited number of sites and show that there is little correlation between the two sets of sites operating in each experimental method: across both materials, only six out of 73 sites active for immersion freezing nucleation were also active for deposition nucleation. Clearly, different properties determine the activity of nucleation sites for each mode, and we use the pore condensation and freezing concept to argue that effective deposition sites have size and/or geometry requirements not of relevance to effective immersion freezing sites. Hence, the ability to nucleate is pathway dependent, and the mode of nucleation has to be explicitly considered when applying experimental data in cloud models. [Abstract copyright: Copyright © 2021 the Author(s). Published by PNAS.

The mean free path of ionizing photons at 5 &lt; z &lt; 6: evidence for rapid evolution near reionization

The mean free path of ionizing photons, λmfp, is a key factor in the photoionization of the intergalactic medium (IGM). At z ≳ 5, however, λmfp may be short enough that measurements towards QSOs are biased by the QSO proximity effect. We present new direct measurements of λmfp that address this bias and extend up to z ∼ 6 for the first time. Our measurements at z ∼ 5 are based on data from the Giant Gemini GMOS survey and new Keck LRIS observations of low-luminosity QSOs. At z ∼ 6 we use QSO spectra from Keck ESI and VLT X-Shooter. We measure λmfp=9.09+1.62−1.28 proper Mpc and 0.75+0.65−0.45 proper Mpc (68 per cent confidence) at z = 5.1 and 6.0, respectively. The results at z = 5.1 are consistent with existing measurements, suggesting that bias from the proximity effect is minor at this redshift. At z = 6.0, however, we find that neglecting the proximity effect biases the result high by a factor of two or more. Our measurement at z = 6.0 falls well below extrapolations from lower redshifts, indicating rapid evolution in λmfp over 5 < z < 6. This evolution disfavours models in which reionization ended early enough that the IGM had time to fully relax hydrodynamically by z = 6, but is qualitatively consistent with models wherein reionization completed at z = 6 or even significantly later. Our mean free path results are most consistent with late reionization models wherein the IGM is still 20 per cent neutral at z = 6, although our measurement at z = 6.0 is even lower than these models prefer