137 research outputs found
Competition between Diffusion and Fragmentation: An Important Evolutionary Process of Nature
We investigate systems of nature where the common physical processes
diffusion and fragmentation compete. We derive a rate equation for the size
distribution of fragments. The equation leads to a third order differential
equation which we solve exactly in terms of Bessel functions. The stationary
state is a universal Bessel distribution described by one parameter, which fits
perfectly experimental data from two very different system of nature, namely,
the distribution of ice crystal sizes from the Greenland ice sheet and the
length distribution of alpha-helices in proteins.Comment: 4 pages, 3 figures, (minor changes
Functional Characterization of Water Transport and Cellular Localization of Three Aquaporin Paralogs in the Salmonid Intestine
Intestinal water absorption is greatly enhanced in salmonids upon acclimation from freshwater (FW) to seawater (SW); however, the molecular mechanism for water transport is unknown. We conducted a pharmacological characterization of water absorption in the rainbow trout intestine along with an investigation of the distribution and cellular localization of three aquaporins (Aqp1aa, -1ab, and -8ab) in pyloric caeca, middle (M), and posterior (P) intestine of the Atlantic salmon. In vitro iso-osmotic water absorption (Jv) was higher in SW than FW-trout and was inhibited by (mmol L−1): 0.1 KCN (41%), 0.1 ouabain (72%), and 0.1 bumetanide (82%) suggesting that active transport, Na+, K+-ATPase and Na+, K+, 2Cl−-co-transport are involved in establishing the driving gradient for water transport. Jv was also inhibited by 1 mmol L−1 HgCl2, serosally (23% in M and 44% in P), mucosally (27% in M), or both (61% in M and 58% in P), suggesting involvement of both apical and basolateral aquaporins in water transport. The inhibition was antagonized by 5 mmol L−1 mercaptoethanol. By comparison, 10 mmol L−1 mucosal tetraethylammonium, an inhibitor of certain aquaporins, inhibited Jv by 20%. In the presence of glucose, mucosal addition of phloridzin inhibited water transport by 20%, suggesting that water transport is partially linked to the Na+-glucose co-transporter. Using polyclonal antibodies against salmon Aqp1aa, -1ab, and -8ab, we detected Aqp1aa, and -1ab immunoreactivity in the brush border and sub-apical region of enterocytes in all intestinal segments. The Aqp8ab antibody showed a particularly strong immunoreaction in the brush border and sub-apical region of enterocytes throughout the intestine and also stained lateral membranes and peri-nuclear regions though at lower intensity. The present localization of three aquaporins in both apical and lateral membranes of salmonid enterocytes facilitates a model for transcellular water transport in the intestine of SW-acclimated salmonids
Diffusion, Fragmentation and Coagulation Processes: Analytical and Numerical Results
We formulate dynamical rate equations for physical processes driven by a
combination of diffusive growth, size fragmentation and fragment coagulation.
Initially, we consider processes where coagulation is absent. In this case we
solve the rate equation exactly leading to size distributions of Bessel type
which fall off as for large -values. Moreover, we provide
explicit formulas for the expansion coefficients in terms of Airy functions.
Introducing the coagulation term, the full non-linear model is mapped exactly
onto a Riccati equation that enables us to derive various asymptotic solutions
for the distribution function. In particular, we find a standard exponential
decay, , for large , and observe a crossover from the Bessel
function for intermediate values of . These findings are checked by
numerical simulations and we find perfect agreement between the theoretical
predictions and numerical results.Comment: (28 pages, 6 figures, v2+v3 minor corrections
Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study
Objective To examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction
Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study
Objectives To evaluate the individual risk factors composing the CHADS2 (Congestive heart failure, Hypertension, Age≥75 years, Diabetes, previous Stroke) score and the CHA2DS2-VASc (CHA2DS2-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism
Mutations in the potassium channel subunit KCNE1 are associated with early-onset familial atrial fibrillation
<p>Abstract</p> <p>Background</p> <p>Atrial fibrillation (AF) is the most common arrhythmia. The potassium current I<sub>Ks </sub>is essential for cardiac repolarization. Gain-of-function mutations in K<sub>V</sub>7.1, the pore-forming α-subunit of the I<sub>Ks </sub>channel, have been associated with AF. We hypothesized that early-onset lone AF is associated with mutations in the I<sub>Ks </sub>channel regulatory subunit KCNE1.</p> <p>Methods</p> <p>In 209 unrelated early-onset lone AF patients (< 40 years) the entire coding sequence of <it>KCNE1 </it>was bidirectionally sequenced. We analyzed the identified KCNE1 mutants electrophysiologically in heterologous expression systems.</p> <p>Results</p> <p>Two non-synonymous mutations G25V and G60D were found in <it>KCNE1 </it>that were not present in the control group (n = 432 alleles) and that have not previously been reported in any publicly available databases or in the exom variant server holding exom data from more than 10.000 alleles. Proband 1 (female, age 45, G25V) had onset of paroxysmal AF at the age of 39 years. Proband 2 (G60D) was diagnosed with lone AF at the age of 33 years. The patient has inherited the mutation from his mother, who also has AF. Both probands had no mutations in genes previously associated with AF. In heterologous expression systems, both mutants showed significant gain-of-function for I<sub>Ks </sub>both with respect to steady-state current levels, kinetic parameters, and heart rate-dependent modulation.</p> <p>Conclusions</p> <p>Mutations in K<sub>V</sub>7.1 leading to gain-of-function of I<sub>Ks </sub>current have previously been described in lone AF, yet this is the first time a mutation in the beta-subunit <it>KCNE1 </it>is associated with the disease. This finding further supports the hypothesis that increased potassium current enhances AF susceptibility.</p
Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest
Introduction: A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, to increase the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed to investigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population.Materials and Methods: A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40–50] years, 49% males), with available digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.6–13.4] years. Data on outcomes were collected from Danish administrative healthcare registries. Furthermore, ~400,000 persons from UK Biobank were investigated for associations between the three loci and cardiac arrest/ventricular fibrillation (VF).Results: Homozygote carriers of the C allele in rs6800541 intronic to SCN10A had a significantly larger J-point elevation (JPE) compared with wildtype carriers (11 vs. 6 μV, P < 0.001). There was an additive effect of carrying multiple BrS-associated risk alleles with an increased JPE in lead V1. None of the BrS-associated genetic loci predisposed to syncope, atrial fibrillation, or total mortality in the general Danish population. The rs9388451 genetic locus adjacent to the HEY2 gene was associated with cardiac arrest/VF in an analysis using the UK Biobank study (odds ratio = 1.13 (95% confidence interval: 1.08–1.18), P = 0.006).Conclusions: BrS-associated risk alleles increase the JPE in lead V1 in an additive manner, but was not associated with increased mortality or syncope in the general population of Denmark. However, the HEY2 risk allele increased the risk of cardiac arrest/VF in the larger population study of UK Biobank indicating an important role of this common genetic locus
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