Insights into the molecular interaction between sucrose and α-chymotrypsin

© 2018 Elsevier B.V. One of the most important purposes of enzyme engineering is to increase the thermal and kinetic stability of enzymes, which is an important factor for using enzymes in industry. The purpose of the present study is to achieve a higher thermal stability of α-chymotrypsin (α-Chy) by modification of the solvent environment. The influence of sucrose was investigated using thermal denaturation analysis, fluorescence spectroscopy, circular dichroism, molecular docking and molecular dynamics (MD) simulations. The results point to the effect of sucrose in enhancing the α-Chy stability. Fluorescence spectroscopy revealed one binding site that is dominated by static quenching. Molecular docking and MD simulation results indicate that hydrogen bonding and van der Waals forces play a major role in stabilizing the complex. Tm of this complex was enhanced due to the higher H-bond formation and the lower surface hydrophobicity after sucrose modification. The results show the ability of sucrose in protecting the native structural conformation of α-Chy. Sucrose was preferentially excluded from the surface of α-Chy which is explained by the higher tendency of water toward favorable interactions with the functional groups of α-Chy than with sucrose

Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events

Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 +/- 2,269 vs. 538 +/- 1,150, p 400, 3.5 (1.9-5.4; p = 0.007) for scores > 800 and 5.9 (3.7-7.8; p = 0.005) for scores > 1,600. When additionally a PAT volume > 200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores > 400, 4.0 (2.1-5.0; p = 0.006) for scores > 800 and 7.1 (4.1-10.2; p = 0.005) for scores > 1,600. Conclusions:The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification. Copyright (C) 2012 S. Karger AG, Base

Stable stem enabled Shannon entropies distinguish non-coding RNAs from random backgrounds

<p>Abstract</p> <p>Background</p> <p>The computational identification of RNAs in genomic sequences requires the identification of signals of RNA sequences. Shannon base pairing entropy is an indicator for RNA secondary structure fold certainty in detection of structural, non-coding RNAs (ncRNAs). Under the Boltzmann ensemble of secondary structures, the probability of a base pair is estimated from its frequency across all the alternative equilibrium structures. However, such an entropy has yet to deliver the desired performance for distinguishing ncRNAs from random sequences. Developing novel methods to improve the entropy measure performance may result in more effective ncRNA gene finding based on structure detection.</p> <p>Results</p> <p>This paper shows that the measuring performance of base pairing entropy can be significantly improved with a constrained secondary structure ensemble in which only canonical base pairs are assumed to occur in energetically stable stems in a fold. This constraint actually reduces the space of the secondary structure and may lower the probabilities of base pairs unfavorable to the native fold. Indeed, base pairing entropies computed with this constrained model demonstrate substantially narrowed gaps of Z-scores between ncRNAs, as well as drastic increases in the Z-score for all 13 tested ncRNA sets, compared to shuffled sequences.</p> <p>Conclusions</p> <p>These results suggest the viability of developing effective structure-based ncRNA gene finding methods by investigating secondary structure ensembles of ncRNAs.</p

Incremental value of the CT coronary calcium score for the prediction of coronary artery disease

Objectives:: To validate published prediction models for the presence of obstructive coronary artery disease (CAD) in patients with new onset stable typical or atypical angina pectoris and to assess the incremental value of the CT coronary calcium score (CTCS). Methods:: We searched the literature for clinical prediction rules for the diagnosis of obstructive CAD, defined as≥50% stenosis in at least one vessel on conventional coronary angiography. Significant variables were re-analysed in our dataset of 254 patients with logistic regression. CTCS was subsequently included in the models. The area under the receiver operating characteristic curve (AUC) was calculated to assess diagnostic performance. Results:: Re-analysing the variables used by Diamond & Forrester yielded an AUC of 0.798, which increased to 0.890 by adding CTCS. For Pryor, Morise 1994, Morise 1997 and Shaw the AUC increased from 0.838 to 0.901, 0.831 to 0.899, 0.840 to 0.898 and 0.833 to 0.899. CTCS significantly improved model performance in each model. Conclusions:: Validation demonstrated good diagnostic performance across all models. CTCS improves the prediction of the presence of obstructive CAD, independent of clinical predictors, and should be considered in its diagnostic work-up. © 2010 The Author(s)

Coronary Artery Calcium Scores: Current Thinking and Clinical Applications

Most incident coronary disease occurs in previously asymptomatic individuals who were considered to be at a lower risk by traditional screening methods. There is a definite advantage if these individuals could be reclassified into a higher risk category, thereby impacting disease outcomes favorably. Coronary artery calcium scores have been recognized as an independent marker for adverse prognosis in coronary disease. Multiple population based studies have acknowledged the shortcomings of risk prediction models such as the Framingham risk score or the Procam score. The science behind coronary calcium is discussed briefly followed by a review of current thinking on calcium scores. An attempt has been made to summarize the appropriate indications and use of calcium scores

Distribution and burden of newly detected coronary artery calcium: Results from the Multi-Ethnic Study of Atherosclerosis

BACKGROUND: The transition from no coronary artery calcium (CAC) to detectable CAC is important, as even mild CAC is associated with increased cardiovascular events. We sought to characterize the anatomical distribution and burden of newly detectable CAC over 10-years follow-up. METHODS: We evaluated 3112 participants (mean age 58, 64% female) with baseline CAC=0 from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants underwent repeat CAC testing at different time intervals (between 2–10 years after baseline) per MESA protocol. Among participants who developed CAC on a follow-up scan, we used logistic regression and marginal probability modeling to describe the coronary distribution and burden of new CAC by age, gender, and race/ethnicity after adjustment for cardiovascular risk factors and time-to-detection. RESULTS: A total of 1125 participants developed detectable CAC during follow-up with mean time-to-detection of 6.1 ± 3 years. New CAC was most commonly isolated to one vessel (72% of participants), with the left anterior descending (44% of total) most commonly affected followed by the right coronary (12%), left circumflex (10%) and left main (6%). These patterns were similar across age, gender, and race/ethnicity. In multivariable models, residual predictors of multi-vessel CAC (28% of total) included male gender, African-American or Hispanic race/ethnicity, hypertension, obesity, and diabetes. At the first detection of CAC>0, burden was usually low with median Agatston CAC score of 7.1, and <5% with CAC scores >100. CONCLUSION: New onset CAC most commonly involves just one vessel, occurs in the left anterior descending artery, has low CAC burden. New CAC can be detected at an early stage when aggressive preventive strategies may provide benefit

Insights into the molecular interaction between sucrose and α-chymotrypsin

© 2018 Elsevier B.V. One of the most important purposes of enzyme engineering is to increase the thermal and kinetic stability of enzymes, which is an important factor for using enzymes in industry. The purpose of the present study is to achieve a higher thermal stability of α-chymotrypsin (α-Chy) by modification of the solvent environment. The influence of sucrose was investigated using thermal denaturation analysis, fluorescence spectroscopy, circular dichroism, molecular docking and molecular dynamics (MD) simulations. The results point to the effect of sucrose in enhancing the α-Chy stability. Fluorescence spectroscopy revealed one binding site that is dominated by static quenching. Molecular docking and MD simulation results indicate that hydrogen bonding and van der Waals forces play a major role in stabilizing the complex. Tm of this complex was enhanced due to the higher H-bond formation and the lower surface hydrophobicity after sucrose modification. The results show the ability of sucrose in protecting the native structural conformation of α-Chy. Sucrose was preferentially excluded from the surface of α-Chy which is explained by the higher tendency of water toward favorable interactions with the functional groups of α-Chy than with sucrose