Fluctuating-friction molecular motors

We show that the correlated stochastic fluctuation of the friction coefficient can give rise to long-range directional motion of a particle undergoing Brownian random walk in a constant periodic energy potential landscape. The occurrence of this motion requires the presence of two additional independent bodies interacting with the particle via friction and via the energy potential, respectively, which can move relative to each other. Such three-body system generalizes the classical Brownian ratchet mechanism, which requires only two interacting bodies. In particular, we describe a simple two-level model of fluctuating-friction molecular motor that can be solved analytically. In our previous work [M.K., L.M and D.P. 2000 J. Nonlinear Opt. Phys. Mater. vol. 9, 157] this model has been first applied to understanding the fundamental mechanism of the photoinduced reorientation of dye-doped liquid crystals. Applications of the same idea to other fields such as molecular biology and nanotechnology can however be envisioned. As an example, in this paper we work out a model of the actomyosin system based on the fluctuating-friction mechanism.Comment: to be published in J. Physics Condensed Matter (http://www.iop.org/Journals/JPhysCM

Operation Moshtarak and the manufacture of credible, “heroic” warfare

Richard Lance Keeble argues that Fleet Street’s coverage of the Afghan conflict has served largely to promote the interests of the military/industrial/media complex – and marginalise the views of the public who have consistently appealed in polls for the troops to be brought back hom

Kinesin-2 KIF3AC and KIF3AB Can Drive Long-Range Transport along Microtubules

AbstractMammalian KIF3AC is classified as a heterotrimeric kinesin-2 that is best known for organelle transport in neurons, yet in vitro studies to characterize its single molecule behavior are lacking. The results presented show that a KIF3AC motor that includes the native helix α7 sequence for coiled-coil formation is highly processive with run lengths of ∼1.23 μm and matching those exhibited by conventional kinesin-1. This result was unexpected because KIF3AC exhibits the canonical kinesin-2 neck-linker sequence that has been reported to be responsible for shorter run lengths observed for another heterotrimeric kinesin-2, KIF3AB. However, KIF3AB with its native neck linker and helix α7 is also highly processive with run lengths of ∼1.62 μm and exceeding those of KIF3AC and kinesin-1. Loop L11, a component of the microtubule-motor interface and implicated in activating ADP release upon microtubule collision, is significantly extended in KIF3C as compared with other kinesins. A KIF3AC encoding a truncation in KIF3C loop L11 (KIF3ACΔL11) exhibited longer run lengths at ∼1.55 μm than wild-type KIF3AC and were more similar to KIF3AB run lengths, suggesting that L11 also contributes to tuning motor processivity. The steady-state ATPase results show that shortening L11 does not alter kcat, consistent with the observation that single molecule velocities are not affected by this truncation. However, shortening loop L11 of KIF3C significantly increases the microtubule affinity of KIF3ACΔL11, revealing another structural and mechanistic property that can modulate processivity. The results presented provide new, to our knowledge, insights to understand structure-function relationships governing processivity and a better understanding of the potential of KIF3AC for long-distance transport in neurons

Perceived need of, and interest in, HIV pre-exposure prophylaxis amongst men who have sex with men attending three sexual health clinics in London, UK

HIV pre-exposure prophylaxis (PrEP) has proven efficacy in reducing the risk of HIV infection in men who have sex with men (MSM), but has not yet been commissioned in the UK. The aim of this study was to investigate perceived need and benefit (or experience of) PrEP among HIV-negative MSM attending sexual health clinics. HIV-negative MSM attending three sexual health centres in London, UK were opportunistically invited to complete a questionnaire. Data collected comprised demographic data and sexual and drug use behaviours as well as questions regarding perceptions of risk and need for PrEP. Logistic regression analysis was undertaken to identify variables predicting acceptability of, and intention to use, PrEP. In addition, data were gathered in respondents already taking PrEP. Eight hundred and thirty-nine questionnaires were analysed. The median age of respondents was 35 years (IQR 28–41, range 18–78), 650 (77%) were of white ethnicity and 649 (77%) had a university education. Four hundred and fifty-six (54%) reported at least one episode of condomless anal sex in the preceding three months, 437 (52%) reported recreational drug use in the preceding three months and 311 (37%) had been diagnosed with a sexually transmitted infection within the preceding six months. Four hundred and sixty-three (64%) of 726 strongly agreed with the statement ‘I think I would benefit from PrEP’. Multivariate logistic regression analysis demonstrated that having receptive anal intercourse (RAI) without condoms, having an awareness of the risk of unprotected RAI and having belief in the effectiveness of PrEP were independent predictors for someone thinking they would benefit from taking PrEP. Eight percent of respondents (59/724) had already taken or were currently taking PrEP. The results suggest that individuals at risk are likely to perceive themselves as benefiting from PrEP. The majority perceived their risk of acquiring HIV and benefit from PrEP accurately. Overall they appeared to have little concern over the use of PrEP and generally positive attitudes. Further investigation is warranted to understand why those at risk do not perceive benefit from PrEP

Paired comparisons of carbon exchange between undisturbed and regenerating stands in four managed forests in Europe

The effects of harvest on European forest net ecosystem exchange (NEE) of carbon and its photosynthetic and respiratory components (GPP (gross primary production) and TER (total ecosystem respiration)) were examined by comparing four pairs of mature/harvested sites in Europe via a combination of eddy covariance measurements and empirical modeling. Three of the comparisons represented high coniferous forestry (spruce in Britain, and pines in Finland and France), while a coppice-with-standard oak plantation was examined in Italy. While every comparison revealed that harvesting converted a mature forest carbon sink into a carbon source of similar magnitude, the mechanisms by which this occurred were very different according to species or management practice. In Britain, Finland, and France the annual sink (source) strength for mature (clear-cut) stands was estimated at 496 (112), 138 (239), and 222 (225) g C m−2, respectively, with 381 (427) g C m−2 for the mature (coppiced) stand in Italy. In all three cases of high forestry in Britain, Finland, and France, clear-cutting crippled the photosynthetic capacity of the ecosystem – with mature (clear-cut) GPP of 1970 (988), 1010 (363), and 1600 (602) g C m−2– and also reduced ecosystem respiration to a lesser degree – TER of 1385 (1100), 839 (603), and 1415 (878) g C m−2, respectively. By contrast, harvesting of the coppice oak system provoked a burst in respiration – with mature (clear-cut) TER estimated at 1160 (2220) gC m−2– which endured for the 3 years sampled postharvest. The harvest disturbance also reduced GPP in the coppice system – with mature (clear-cut) GPP of 1600 (1420) g C m−2– but to a lesser extent than in the coniferous forests, and with near-complete recovery within a few years. Understanding the effects of harvest on the carbon balance of European forest systems is a necessary step towards characterizing carbon exchange for timberlands on large scales

An unfolding signifier: London's Baltic Exchange in Tallinn

In the summer of 2007 an unusual cargo arrived at Muuga and Paldiski harbors outside Tallinn. It consisted of nearly 50 containers holding over 1,000 tons of building material ranging from marble columns, staircases and fireplaces, to sculpted allegorical figures, wooden paneling and old-fashioned telephone booths. They were once part of the Baltic Exchange in the City of London. Soon they will become facets of the landscape of Tallinn. The following article charts this remarkable story and deploys this fragmented monument to analyze three issues relating to the Estonian capital: the relocation of the ‘Bronze Soldier’, the demolition of the Sakala Culture Center, and Tallinn’s future role as European Cultural Capital in 2011

Thermal Denaturation and Aggregation of Myosin Subfragment 1 Isoforms with Different Essential Light Chains

We compared thermally induced denaturation and aggregation of two isoforms of the isolated myosin head (myosin subfragment 1, S1) containing different “essential” (or “alkali”) light chains, A1 or A2. We applied differential scanning calorimetry (DSC) to investigate the domain structure of these two S1 isoforms. For this purpose, a special calorimetric approach was developed to analyze the DSC profiles of irreversibly denaturing multidomain proteins. Using this approach, we revealed two calorimetric domains in the S1 molecule, the more thermostable domain denaturing in two steps. Comparing the DSC data with temperature dependences of intrinsic fluorescence parameters and S1 ATPase inactivation, we have identified these two calorimetric domains as motor domain and regulatory domain of the myosin head, the motor domain being more thermostable. Some difference between the two S1 isoforms was only revealed by DSC in thermal denaturation of the regulatory domain. We also applied dynamic light scattering (DLS) to analyze the aggregation of S1 isoforms induced by their thermal denaturation. We have found no appreciable difference between these S1 isoforms in their aggregation properties under ionic strength conditions close to those in the muscle fiber (in the presence of 100 mM KCl). Under these conditions kinetics of this process was independent of protein concentration, and the aggregation rate was limited by irreversible denaturation of the S1 motor domain