Stability of adhesion clusters under constant force

We solve the stochastic equations for a cluster of parallel bonds with shared constant loading, rebinding and the completely dissociated state as an absorbing boundary. In the small force regime, cluster lifetime grows only logarithmically with bond number for weak rebinding, but exponentially for strong rebinding. Therefore rebinding is essential to ensure physiological lifetimes. The number of bonds decays exponentially with time for most cases, but in the intermediate force regime, a small increase in loading can lead to much faster decay. This effect might be used by cell-matrix adhesions to induce signaling events through cytoskeletal loading.Comment: Revtex, 4 pages, 4 Postscript files include

Probing molecular free energy landscapes by periodic loading

Single molecule pulling experiments provide information about interactions in biomolecules that cannot be obtained by any other method. However, the reconstruction of the molecule's free energy profile from the experimental data is still a challenge, in particular for the unstable barrier regions. We propose a new method for obtaining the full profile by introducing a periodic ramp and using Jarzynski's identity for obtaining equilibrium quantities from non-equilibrium data. Our simulated experiments show that this method delivers significant more accurate data than previous methods, under the constraint of equal experimental effort.Comment: 4 pages, 3 figure

Electrophysiological characterization of the hyperdirect pathway and its functional relevance for subthalamic deep brain stimulation

The subthalamic nucleus (STN) receives input from various cortical areas via hyperdirect pathway (HDP) which bypasses the basal-ganglia loop. Recently, the HDP has gained increasing interest, because of its relevance for STN deep brain stimulation (DBS). To understand the HDP's role cortical responses evoked by STN-DBS have been investigated. These responses have short (<2 ms), medium (2–15 ms), and long (20–70 ms) latencies. Medium-latency responses are supposed to represent antidromic cortical activations via HDP. Together with long-latency responses the medium responses can potentially be used as biomarker of DBS efficacy as well as side effects. We here propose that the activation sequence of the cortical evoked responses can be conceptualized as high frequency oscillations (HFO) for signal analysis. HFO might therefore serve as marker for antidromic activation. Using existing knowledge on HFO recordings, this approach allows data analyses and physiological modeling to advance the pathophysiological understanding of cortical DBS-evoked high-frequency activity

Les problèmes de comportement, les représentations d’attachement et le parcours de placement d’enfants relevant de la protection de l’enfance

International audienc

Corneal collagen cross-linking (CXL) for the treatment of melting keratitis in cats and dogs: a pilot study

Objective UV-A/riboflavin cross-linking (CXL) of corneal collagen fibers is an established, highly promising therapy for corneal melting in physician-based ophthalmology. A prospective pilot study was conducted to demonstrate proof of principle of this novel method for the treatment of melting corneal ulcers in dogs and cats. Procedures After obtaining owner consent, CXL was performed in three cats and three dogs with corneal melting, which either affected the entire corneal surface or was resistant to conventional antibiotic and anticollagenolytic therapy, or affected parts or all of the corneal surface. Medical therapy was continued in all patients. The available follow-up ranged from 2 to 22.5 months and involved slit-lamp examination, fluorescein staining, and photographic documentation during all rechecks. Results Surgical stabilization of the cornea was not necessary in any case, because progression of corneal melting was arrested in all cases within 1–20 days of CXL treatment. Corneal re-epithelization occurred within 7–40 days in all eyes. At 40 days after CXL, all eyes presented a quiescent corneal state without signs of active inflammation and with beginning scar formation. The complications observed in three of the six animals included a corneal sequestrum, superficial corneal stromal pigmentation, and bullous keratopathy. Conclusions This study shows the feasibility of CXL to treat progressive corneal melting in veterinary patients. CXL may represent a cost-efficient and safe alternative therapy in the treatment for corneal melting in veterinary ophthalmology. More investigations comparing the effectivity and complication rate of CXL to those of standard medical treatment are necessary

The Kundu--Eckhaus equation and its discretizations

In this article we show that the complex Burgers and the Kundu--Eckhaus equations are related by a Miura transformation. We use this relation to discretize the Kundu--Eckhaus equation.Comment: 10 page

Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries.

In the setting of type-2 diabetes, there are declines of structural stability and functionality of blood capillaries and red blood cells (RBCs), increasing the risk for microcirculatory disturbances. Correcting hyperglycemia is not entirely effective at reestablishing normal cellular metabolism and function. Therefore, identification of pathological changes occurring before the development of overt hyperglycemia may lead to novel therapeutic targets for reducing the risk of microvascular dysfunction. Here we determine whether RBC-capillary interactions are altered by prediabetic hypersecretion of amylin, an amyloid forming hormone co-synthesized with insulin, and is reversed by endothelial cell-secreted epoxyeicosatrienoic acids. In patients, we found amylin deposition in RBCs in association with type-2 diabetes, heart failure, cancer and stroke. Amylin-coated RBCs have altered shape and reduced functional (non-glycated) hemoglobin. Amylin-coated RBCs administered intravenously in control rats upregulated erythropoietin and renal arginase expression and activity. We also found that diabetic rats expressing amyloid-forming human amylin in the pancreas (the HIP rat model) have increased tissue levels of hypoxia-inducible transcription factors, compared to diabetic rats that express non-amyloid forming rat amylin (the UCD rat model). Upregulation of erythropoietin correlated with lower hematocrit in the HIP model indicating pathologic erythropoiesis. In the HIP model, pharmacological upregulation of endogenous epoxyeicosatrienoic acids protected the renal microvasculature against amylin deposition and also reduced renal accumulation of HIFs. Thus, prediabetes induces dysregulation of amylin homeostasis and promotes amylin deposition in RBCs and the microvasculature altering RBC-capillary interaction leading to activation of hypoxia signaling pathways and pathologic erythropoiesis. Hence, dysregulation of amylin homeostasis could be a therapeutic target for ameliorating diabetic vascular complications

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

The Global School Adaptation score: a new neurodevelopmental assessment tool for very preterm children at five years of age

Objective To determine the usefulness of a neurodevelopmental assessment tool consisting of a questionnaire administered to teachers to measure the Global School Adaptation (GSA) scores of very preterm children at the age of 5 years. Study design A sample of 445 very preterm children (&lt;35 weeks of gestation) was assessed at 5 years of age using GSA and IQ scores. According to the consistency between the scores, children were determined to be well classified, intermediately classified, or misclassified. The differences between groups were assessed through univariate and multivariate logistic regression. Results The GSA score was highly or intermediately consistent with the IQ score for 89.2% of the children, and 10.8% were considered misclassified. Children with a higher GSA than IQ score had more autonomy and self-confidence (P &lt; .01), and those with a lower GSA than IQ score had more behavioral problems (P &lt; .01). Analysis by logistic regression showed that sex and gestational age significantly affected the consistency between the 2 scores. Thus, girls were less likely to have a lower GSA than IQ score (aOR = 0.45; 95% CI: 0.24-0.84; P = .01), and a lower gestational age significantly increased the likelihood of having a higher GSA than IQ score (for children born between 24 and 28 weeks of gestation: aOR = 2.70; 95% CI: 1.23-5.92; P = .01). Conclusions The GSA score is a simple, inexpensive, and reliable screening tool for assessing neurodevelopment in very preterm children at 5 years of age