Random bursts determine dynamics of active filaments

Constituents of living or synthetic active matter have access to a local energy supply that serves to keep the system out of thermal equilibrium. The statistical properties of such fluctuating active systems differ from those of their equilibrium counterparts. Using the actin filament gliding assay as a model, we studied how nonthermal distributions emerge in active matter. We found that the basic mechanism involves the interplay between local and random injection of energy, acting as an analog of a thermal heat bath, and nonequilibrium energy dissipation processes associated with sudden jump-like changes in the system’s dynamic variables. We show here how such a mechanism leads to a nonthermal distribution of filament curvatures with a non-Gaussian shape. The experimental curvature statistics and filament relaxation dynamics are reproduced quantitatively by stochastic computer simulations and a simple kinetic model.In active systems, perpetual local energy input prevents relaxation into a thermal equilibrium state (1–3). Examples are living matter (4–10) or appropriately reconstituted or synthetic model systems (11–17). It is widely accepted that nonthermal fluctuations play a crucial role for the dynamics of active systems (8, 9, 18–24) and may even cause an apparent violation of the fluctuation-dissipation theorem (11). The physical origin of the violation can be attributed to local tensile stresses generated by myosin minifilaments, as shown by rheological measurements of 3D actin networks consisting of myosin II, actin filaments, and cross-linkers (11). Although this study focused on how the macroscopic properties of the active filament network are altered with respect to its equilibrium counterpart, we consider how local stresses generated by motors mesoscopically affect the dynamics and the conformational statistics of individual filaments. To this end, we use the actin gliding assay (25, 26), which has become a paradigm of active systems. In this assay, actin filaments are moved by individual nonprocessive myosin motors, which are bound to a substrate. We find that motile filaments in this assay display a nonthermal distribution of curvatures with an exponential shape, which is essentially different from its equilibrium counterpart. Based on our observations, we were able to elucidate the origin of the nonthermal fluctuations in the gliding assay and introduce a mechanism that explains how nonthermal distributions may emerge in active matter systems. The mechanism relies on the interplay between local and random input of energy, acting as an analog of a thermal heat bath, and nonequilibrium energy dissipation processes due to sudden jump-like changes in the system’s dynamic variables. We perform stochastic simulations of the filament’s dynamics and provide a rationale drawn from kinetic theory. Both approaches quantitatively reproduce the experimental curvature distribution and correctly predict the relaxation dynamics of the active filament.     

Malignant head and neck paragangliomas in SDHB mutation carriers.

OBJECTIVE: Three of four paraganglioma syndromes (PGLs) have been characterized on a molecular genetic basis. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D (SDHD) gene, PGL 3 is caused by SDHC gene mutations, and PGL 4 is caused by SDHB gene mutations. The objective of this study was to investigate whether PGLs are associated with malignant head and neck paragangliomas (HNPs). STUDY DESIGN AND SETTING: Through November 2005, we screened 195 HNP patients for mutations of the genes SDHB, SDHC, and SDHD. RESULTS: We detected 5 SDHC, 13 SDHB, and 45 SDHD gene mutations. In seven SDHB mutation carriers, there were distant metastases. No signs of metastases were found in SDHC and SDHD patients. One patient with a sporadic HNP presented with locally metastatic disease. CONCLUSIONS: SDHB mutations are associated with a high rate of malignant HNPs. SIGNIFICANCE: In SDHB patients, a three-body region imaging and scintigraphy or DOPA-PET must be performed to exclude metastases.     

Studies of reservoir hosts for Marburg virus

To determine reservoir hosts for Marburg virus (MARV), we examined the fauna of a mine in northeastern Democratic Republic of the Congo. The mine was associated with a protracted outbreak of Marburg hemorrhagic fever during 1998-2000. We found MARV nucleic acid in 12 bats, comprising 3.0%-3.6% of 2 species of insectivorous bat and 1 species of fruit bat. We found antibody to the virus in the serum of 9.7% of 1 of the insectivorous species and in 20.5% of the fruit bat species, but attempts to isolate virus were unsuccessful.     

Are Ambient Ultrafine,Accumulation Mode,and Fine Particles Associated with Adverse Cardiac Responses in Patients Undergoing Cardiac Rehabilitation?

Background: Mechanisms underlying previously reported air pollution and cardiovascular (CV) morbidity associations remain poorly understood.Objectives: We examined associations between markers of pathways thought to underlie these air pollution and CV associations and ambient particle concentrations in postinfarction patients.Methods: We studied 76 patients, from June 2006 to November 2009, who participated in a 10-week cardiac rehabilitation program following a recent (within 3 months) myocardial infarction or unstable angina. Ambient ultrafine particle (UFP; 10-100 nm), accumulation mode particle (AMP; 100-500 nm), and fine particle concentrations (PM2.5; ≤ 2.5 μm in aerodynamic diameter) were monitored continuously. Continuous Holter electrocardiogram (ECG) recordings were made before and during supervised, graded, twice weekly, exercise sessions. A venous blood sample was collected and blood pressure was measured before sessions.Results: Using mixed effects models, we observed adverse changes in rMSSD [square root of the mean of the sum of the squared differences between adjacent normal-to-normal (NN) intervals], SDNN (standard deviation of all NN beat intervals), TpTe (time from peak to end of T-wave), heart rate turbulence, systolic and diastolic blood pressures, C-reactive protein, and fibrinogen associated with interquartile range increases in UFP, AMP, and PM2.5 at 1 or more lag times within the previous 5 days. Exposures were not associated with MeanNN, heart-rate-corrected QT interval duration (QTc), deceleration capacity, and white blood cell count was not associated with UFP, AMP, and PM2.5 at any lag time.Conclusions: In cardiac rehabilitation patients, particles were associated with subclinical decreases in parasympathetic modulation, prolongation of late repolarization duration, increased blood pressure, and systemic inflammation. It is possible that such changes could increase the risk of CV events in this susceptible population.     

Helical twist controls the thickness of F-actin bundles

In the presence of condensing agents such as nonadsorbing polymer, multivalent counter ions, and specific bundling proteins, chiral biopolymers typically form bundles with a finite thickness, rather than phase-separating into a polymer-rich phase. Although short-range repulsive interactions or geometrical frustrations are thought to force the equilibrium bundle size to be limited, the precise mechanism is yet to be resolved. The importance of the tight control of biopolymer bundle size is illustrated by the ubiquitous cytoskeletal actin filament bundles that are crucial for the proper functioning of cells. Using an in vitro model system, we show that size control relies on a mismatch between the helical structure of individual actin filaments and the geometric packing constraints within bundles. Small rigid actin-binding proteins change the twist of filamentous actin (F-actin) in a concentration-dependent manner, resulting in small, well defined bundle thickness up to approximately 20 filaments, comparable to those found in filopodia. Other F-actin cross-linking proteins can subsequently link these small, well organized bundles into larger structures of several hundred filaments, comparable to those found in, for example, Drosophila bristles. The energetic tradeoff between filament twisting and cross-linker binding within a bundle is suggested as a fundamental mechanism by which cells can precisely adjust bundle size and strength.     

Selective Precipitation of Interleukin-4 Using Hydrophobic Ion Pairing: A Method for Improved Analysis of Proteins Formulated with Large Excesses of Human Serum Albumin

In order to ensure the stability of protein pharmaceuticals, human serum albumin (HSA) is often added as an excipient, frequently in large excess. This makes chromatographic analysis of the stability of the active protein difficult. In the case of interleukin-4 (IL-4), separation from HSA can be achieved to some degree by size exclusion chromatography, but some HSA co-elutes with the IL-4. Hydrophobic ion pairing provides a method for selective precipitation of IL-4 from HSA. Hydrophobic ion pairing involves the electrostatic interaction of ionic detergents with oppositely charged polypeptides. Even when HSA is present in fifty-fold excess (w/w), the resulting precipitate contains greater than 70% of the IL-4. Selective precipitation with SDS produces enhancements in IL-4 over HSA of more than 2000-fold. This approach permits subsequent facile analysis of IL-4 by conventional reverse phase HPLC.     

Effects and side effects of hormonal contraceptives in the region of the nose, throat, and ear

The pathomechanism of diseases in the field of oto-rhino-laryngology caused by an hormonal contraceptive therapy are presented on base of a critical literature survey. Complications of oral contraception are proved only for the oral tissue (hyperplastic gingivitis) the larynx and the eustachian tube. Otological (otosclerosis, acute deafness, slowly progressive deafness) and rhinological diseases (Rhinopathia vasomotorica) in women under oral contraception cannot be attributed exclusively to this therapy.