A Signal Processing Method to Explore Similarity in Protein Flexibility

Understanding mechanisms of protein flexibility is of great importance to structural biology. The ability to detect similarities between proteins and their patterns is vital in discovering new information about unknown protein functions. A Distance Constraint Model (DCM) provides a means to generate a variety of flexibility measures based on a given protein structure. Although information about mechanical properties of flexibility is critical for understanding protein function for a given protein, the question of whether certain characteristics are shared across homologous proteins is difficult to assess. For a proper assessment, a quantified measure of similarity is necessary. This paper begins to explore image processing techniques to quantify similarities in signals and images that characterize protein flexibility. The dataset considered here consists of three different families of proteins, with three proteins in each family. The similarities and differences found within flexibility measures across homologous proteins do not align with sequence-based evolutionary methods

Redistribution of Flexibility in Stabilizing Antibody Fragment Mutants Follows Le Chatelier's Principle

Le Châtelier's principle is the cornerstone of our understanding of chemical equilibria. When a system at equilibrium undergoes a change in concentration or thermodynamic state (i.e., temperature, pressure, etc.), La Châtelier's principle states that an equilibrium shift will occur to offset the perturbation and a new equilibrium is established. We demonstrate that the effects of stabilizing mutations on the rigidity ⇔ flexibility equilibrium within the native state ensemble manifest themselves through enthalpy-entropy compensation as the protein structure adjusts to restore the global balance between the two. Specifically, we characterize the effects of mutation to single chain fragments of the anti-lymphotoxin-β receptor antibody using a computational Distance Constraint Model. Statistically significant changes in the distribution of both rigidity and flexibility within the molecular structure is typically observed, where the local perturbations often lead to distal shifts in flexibility and rigidity profiles. Nevertheless, the net gain or loss in flexibility of individual mutants can be skewed. Despite all mutants being exclusively stabilizing in this dataset, increased flexibility is slightly more common than increased rigidity. Mechanistically the redistribution of flexibility is largely controlled by changes in the H-bond network. For example, a stabilizing mutation can induce an increase in rigidity locally due to the formation of new H-bonds, and simultaneously break H-bonds elsewhere leading to increased flexibility distant from the mutation site via Le Châtelier. Increased flexibility within the VH β4/β5 loop is a noteworthy illustration of this long-range effect

Statistical Inference, Distinguishability of Quantum States, And Quantum Entanglement

We argue from the point of view of statistical inference that the quantum relative entropy is a good measure for distinguishing between two quantum states (or two classes of quantum states) described by density matrices. We extend this notion to describe the amount of entanglement between two quantum systems from a statistical point of view. Our measure is independent of the number of entangled systems and their dimensionality.Comment: 11 pages no figures, to appear in Phys. Rev.

Management of aneurysms involving branches of the celiac and superior mesenteric arteries: A comparison of surgical and endovascular therapy

ObjectiveAneurysms involving branches of the superior mesenteric and celiac arteries are uncommon and require proper management to prevent rupture and death. This study compares surgical and endovascular treatment of these aneurysms and analyzes outcome.MethodsPatients at the Mount Sinai Medical Center in New York who were treated for aneurysms in the branches of the celiac artery and superior mesenteric artery were identified through a search of the institution’s medical records and endovascular database. Patient demographics, history, clinical presentation, aneurysm characteristics, treatments, and follow-up outcome were retrospectively recorded. Significant differences between patients treated by surgical or endovascular therapy were determined by using Student’s t test and χ 2 analysis.ResultsBetween January 1, 1991, and July 1, 2005, 59 patients with 61 aneurysms were treated at a single institution. Twenty-four patients had surgical repair, and 35 underwent endovascular treatment, which included coil embolization and stent-graft therapy. Splenic (28) and hepatic (22) artery aneurysms predominated. Eighty-nine percent of splenic artery aneurysms were true aneurysms and were treated by endovascular and surgical procedures in near equal numbers (14 and 11, respectively). Pseudoaneurysms were significantly more likely to be treated by endovascular means (P < .01). The technical success rate of endovascular treatment for aneurysms was 89%, and failures were successfully treated by repeat coil embolization in all patients who presented for retreatment. Patients treated by endovascular techniques had a significantly higher incidence of malignancy than patients treated with open surgical techniques (P = .03). Furthermore, patients treated by endovascular means had a shorter in-hospital length of stay (2.4 vs 6.6 days, P < .001).ConclusionEndovascular management of visceral aneurysms is an effective means of treating aneurysms involving branches of the celiac and superior mesenteric arteries and is particularly useful in patients with comorbidities, including cancer. It is associated with a decreased length of stay in the elective setting, and failure of primary treatment can often be successfully managed percutaneously

Microbiota‐Dependent Metabolite Trimethylamine N‐Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA)

BACKGROUND: Clinical studies implicate trimethylamine N-oxide (TMAO; a gut microbiota-dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population-based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). METHODS AND RESULTS: Data were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985-1986 (n=5115). We randomly sampled 817 participants (aged 33-55 years) who attended examinations in 2000-2001, 2005-2006, and 2010-2011, at which CAC was measured by computed tomography and cIMT (2005-2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000-2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000-2001 and >0 over 10-year follow-up, CAC progression (any increase over 10-year follow-up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000-2001 (n=746) developed detectable CAC. In 2000-2001, median (interquartile range) TMAO was 2.6 (1.8-4.2) μmol/L. In multivariable-adjusted models, TMAO was not associated with 10-year CAC incidence (rate ratio=1.03; 95% CI: 0.71-1.52) or CAC progression (0.97; 0.68-1.38) in Poisson regression, or cIMT (beta coefficient: -0.009; -0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO. CONCLUSIONS: In this population-based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early-middle-aged adults