Complex patterns of spontaneous initiations and terminations of reentrant circulation in a loop of cardiac tissue

A two-component model is developed that consists of a discrete loop of cardiac cells that circulates action potentials together with a cardiac pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and their interactions with the pacer are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability of reentrant circulation (T-bistability) and in some cases, also phase-resetting interactions with the pacer.Comment: 27 pages, 10 figures, 61 references; A version of this paper (same results) is to appear in the Journal of Theoretical Biology; arXiv V2 adds helpful commments to facilitate reading and corrects minor errors in presentatio

The Role of Power-Law Correlated Disorder in the Anderson Metal-Insulator Transition

We study the influence of scale-free correlated disorder on the metal-insulator transition in the Anderson model of localization. We use standard transfer matrix calculations and perform finite-size scaling of the largest inverse Lyapunov exponent to obtain the localization length for respective 3D tight-binding systems. The density of states is obtained from the full spectrum of eigenenergies of the Anderson Hamiltonian. We discuss the phase diagram of the metal-insulator transition and the influence of the correlated disorder on the critical exponents.Comment: 6 pages, 3 figure

Effect of Pulsed Low-Intensity Ultrasonography on Symptom Relief and Tibiofemoral Articular Cartilage Thickness Among Veterans Affairs Enrollees With Knee Osteoarthritis: A Randomized Clinical Trial

Importance: Osteoarthritis (OA) is a major cause of disability in the US, with no approved treatments to slow progression, but animal models suggest that pulsed low-intensity ultrasonography (PLIUS) may promote cartilage growth. Objective: To evaluate the efficacy of PLIUS in providing symptom reduction and decreased loss of tibiofemoral cartilage thickness in patients with knee OA. Design, Setting, and Participants: A phase 2A, sham-controlled, parallel, double-blind randomized clinical trial was conducted at 2 Veterans Affairs hospitals in Salt Lake City, Utah, and San Diego, California, from May 22, 2015, to January 31, 2019. Data were analyzed from June 27, 2020, to October 20, 2020. Participants recruited through the US Department of Veterans Affairs (N = 132) with clinical and radiographic evidence of early knee OA were randomly assigned to receive PLIUS or a sham device, self-administered for 20 minutes daily over the medial compartment of the knee. All enrollees participated in a 4-week prerandomization sham run-in period, followed by a 48-week treatment period. Randomization was stratified by study site and Kellgren-Lawrence grades 1 (n = 15), 2 (n = 51), and 3 (n = 66). Intervention: Participants either received 48 weeks of PLIUS or sham ultrasonography. Main Outcomes and Measures: The trial incorporated 2 coprimary outcomes: symptomatic improvement assessed by Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International Responder Criteria (ie, met if either >50% improvement in pain and function with at least a 20% absolute improvement of at least 2 of the following 3 factors: improvement by at least 20% [pain, function, and patient global assessment] with at least a 10-mm absolute improvement), and cartilage preservation assessed as change in central medial femoral condyle cartilage thickness by magnetic resonance imaging. Intention-to-treat analysis was used. Results: The mean (SD) participant age was 63.6 (10.7) years and 119 were men (90.2%). The mean (SD) duration of OA symptoms was 13.4 (12.3) years. In the PLIUS group, 70.4% (95% CI, 58.2%-82.6%) of the participants experienced symptomatic improvement, compared with 67.3% (95% CI, 54.9%-79.7%) of participants in the sham group (P = .84); there was no statistically significant difference in response rates between the treatment groups, and the between-group rate difference of 3.1% (95% CI, -14.3% to 20.5%) did not meet the predefined 10% threshold for clinically significant symptomatic improvement from application of PLIUS. At 48 weeks of treatment, central medial femoral condyle cartilage thickness decreased by a mean (SD) of 73.8 (168.1) μm in the PLIUS group and by 42.2 (297.0) μm in the sham group. This 48-week mean change between the 2 groups did not reach statistical significance (P = .44), and the between-group 48-week difference of -31.7 μm (95% CI, -129.0 μm to 65.7 μm) did not meet the predefined threshold. There were 99 nonserious adverse events in the PLIUS group and 89 in the sham group during the trial. No serious adverse events were deemed related to the study device. Conclusions and Relevance: PLIUS, as implemented in this study, demonstrated neither symptomatic benefit nor a decrease in loss of tibiofemoral cartilage thickness in knee OA. Trial Registration: ClinicalTrials.gov Identifier: NCT02034409.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Stimulation of the cytosolic receptor for peptidoglycan, Nod1, by infection with Chlamydia trachomatis or Chlamydia muridarum.

International audienceInfection of epithelial cells by the intracellular pathogen, Chlamydia trachomatis, leads to activation of NF-kappaB and secretion of pro-inflammatory cytokines. We find that overexpression of a dominant-negative Nod1 or depletion of Nod1 by RNA interference inhibits partially the activation of NF-kappaB during chlamydial infection in vitro, suggesting that Nod1 can detect the presence of Chlamydia. In parallel, there is a larger increase in the expression of pro-inflammatory genes following Chlamydia infection when primary fibroblasts are isolated from wild-type mice than from Nod1-deficient mice. The Chlamydia genome encodes all the putative enzymes required for proteoglycan synthesis, but proteoglycan from Chlamydia has never been detected biochemically. Since Nod1 is a ubiquitous cytosolic receptor for peptidoglycan from Gram-negative bacteria, our results suggest that C. trachomatis and C. muridarum do in fact produce at least the rudimentary proteoglycan motif recognized by Nod1. Nonetheless, Nod1 deficiency has no effect on the efficiency of infection, the intensity of cytokine secretion, or pathology in vaginally infected mice, compared with wild-type controls. Similarly, Rip2, a downstream mediator of Nod1, Toll-like receptor (TLR)-2, and TLR4, increases only slightly the intensity of chlamydial infection in vivo and has a very mild effect on the immune response and pathology. Thus, Chlamydia may not produce sufficient peptidoglycan to stimulate Nod1-dependent pathways efficiently in infected animals, or other receptors of the innate immune system may compensate for the absence of Nod1 during Chlamydia infection in vivo

A simple mechanistic model of seed dispersal, predation and plant establishment: Janzen-Connell and beyond

1. Although, in nature, seed dispersal usually declines with distance from the source, seedling establishment patterns are highly variable. An increase in seed survival can lead to either hump-shaped (Janzen-Connell (J-C) pattern) or declining (Hubbell pattern) establishment with distance from seed source, but declining establishment can also be generated if survival decreases with distance (McCanny pattern). Pathogens and seed predators are considered to be major mortality agents structuring recruitment patterns, but it is unclear how well predation alone can explain variation in these patterns. 2. We introduce a simple mechanistic model showing that distance and density-dependent seed predation can generate all of the observed recruitment patterns. Our approach provides the first mathematical reconstruction of conceptual models previously considered to be based on contrasting underlying mechanisms. Three easily measurable quantities (the proportion of seeds escaping predation at the source, and the mean distance from the source of dispersed seeds and of predators’ activity) can be used to test for consistency with the J-C pattern. The association between recruitment patterns and plant (dispersal) and animal (predation) characteristics is robust with respect to parameter values and various functional forms. 3. The model shows that the J-C pattern can occur only if the mean distance over which predators are active is lower than that over which seeds are dispersed, corresponding to a system with host-specific, or immobile, seed predators (often invertebrates) that are restricted to areas of high seed density near adult plants, and therefore selecting for longer dispersal distances of seeds. 4.The Hubbell pattern is generated by the model when dispersal and predation distances are of equivalent magnitudes. The McCanny pattern emerges if more generalized, or more mobile, seed predators (often vertebrates) are attracted to the adult trees but also tend to forage farther away, thereby selecting for short dispersal distances that generate high densities needed to satiate seed predators. 5.The model also predicts that the total number of seeds surviving predation is lowest at intermediate distances, suggesting that distance-dependent predation promotes either short or long dispersal distances, or both (dimorphism)