AFM pulling and the folding of donor-acceptor oligorotaxanes: phenomenology and interpretation

The thermodynamic driving force in the self-assembly of the secondary structure of a class of donor-acceptor oligorotaxanes is elucidated by means of molecular dynamics simulations of equilibrium isometric single-molecule force spectroscopy AFM experiments. The oligorotaxanes consist of cyclobis(paraquat-\emph{p}-phenylene) rings threaded onto an oligomer of 1,5-dioxynaphthalenes linked by polyethers. The simulations are performed in a high dielectric medium using MM3 as the force field. The resulting force vs. extension isotherms show a mechanically unstable region in which the molecule unfolds and, for selected extensions, blinks in the force measurements between a high-force and a low-force regime. From the force vs. extension data the molecular potential of mean force is reconstructed using the weighted histogram analysis method and decomposed into energetic and entropic contributions. The simulations indicate that the folding of the oligorotaxanes is energetically favored but entropically penalized, with the energetic contributions overcoming the entropy penalty and effectively driving the self-assembly. In addition, an analogy between the single-molecule folding/unfolding events driven by the AFM tip and the thermodynamic theory of first-order phase transitions is discussed and general conditions, on the molecule and the cantilever, for the emergence of mechanical instabilities and blinks in the force measurements in equilibrium isometric pulling experiments are presented. In particular, it is shown that the mechanical stability properties observed during the extension are intimately related to the fluctuations in the force measurements.Comment: 42 pages, 17 figures, accepted to the Journal of Chemical Physic

Phase resolved PLIF and chemiluminescence for measuring combustion dynamics

Transient behavior of combustion systems has long been a subject of both fundamental and practical concerns. Extreme cases of very rapid changes include the ignition of reacting mixtures and detonation. At the other extreme is a wide range of quasi-steady changes of behavior, for example adjustments of the operating point of a combustion chamber. Between the limiting cases of 'infinitely fast' and 'infinitesimally slow' lie important fundamental problems of time-dependent behavior and a wide array of practical applications. Among the latter are combustion instabilities and their active control, a primary motivation for the work reported in this paper. Owing to the complicated chemistry, chemical kinetics and flow dynamics of actual combustion systems, numerical simulations of their behavior remains in a relatively primitive state. Even as that situation continually improves, it is an essential part of the field that methods of measuring true dynamical behavior be developed to provide results having both fine spatial resolution and accuracy in time. This paper is a progress report of recent research carried out in the Jet Propulsion Center of the California Institute of Technology

HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1

An estimated 10–20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle. The regulatory gene Tax-1 is required for efficient virus replication, as it drives transcription of viral gene products, and has also been demonstrated to play a key role in the pathogenesis of the virus. Several studies have identified a PDZ binding motif (PBM) at the carboxyl terminus of Tax-1 and demonstrated the importance of this domain for HTLV-1 induced cellular transformation. Using a mass spectrometry-based proteomics approach we identified sorting nexin 27 (SNX27) as a novel interacting partner of Tax-1. Further, we demonstrated that their interaction is mediated by the Tax-1 PBM and SNX27 PDZ domains. SNX27 has been shown to promote the plasma membrane localization of glucose transport 1 (GLUT1), one of the receptor molecules of the HTLV-1 virus, and the receptor molecule required for HTLV-1 fusion and entry. We postulated that Tax-1 alters GLUT1 localization via its interaction with SNX27. We demonstrate that over expression of Tax-1 in cells causes a reduction of GLUT1 on the plasma membrane. Furthermore, we show that knockdown of SNX27 results in increased virion release and decreased HTLV-1 infectivity. Collectively, we demonstrate the first known mechanism by which HTLV-1 regulates a receptor molecule post-infection.</div

Region Foreign Economic Relations as a Factor of Reindustiralization

At present, the strengthening vector of the developing economies, in particular, of the countries of Eurasian Economic Union and BRICS, in the geographic structure of Russian foreign economic activity is observed. The subject matter of the article is to see, how the development of this direction can be economically favorable. For this purpose, the forms and degree of the development of economic partnership including collaboration with the Russian regions are investigated. The agreements on the economic partnership with the regions of partner countries of Russia, their production relations are considered. The analysis of foreign trade shows that in the case of the partner countries within Eurasian integration and the BRICS group — Russian economy gets the high possibility to become the supplier of products of relatively high degree of processing which is the key factor of development of its processing industry, i.e. the factor of reindustrialization and export-oriented import substitution.The article has been prepared within the project of fundamental research of the Ural Branch of the Russian Academy of Sciences (20152017) No. 15-14-7-13 “Scenario approaches to realization of Ural vector of management and development of the Russian Arctic in terms of world instability”

How does HTLV-1 cause adult T-cell leukaemia/lymphoma (ATL)?

A typical person infected with the retrovirus human T-lymphotropic virus type 1 (HTLV-1) carries tens of thousands of clones of HTLV-1-infected T lymphocytes, each clone distinguished by a unique integration site of the provirus in the host genome. However, only 5% of infected people develop the malignant disease adult T cell leukaemia/lymphoma, usually more than 50 years after becoming infected. We review the host and viral factors that cause this aggressive disease

Strengthening collective action to address resource conflict in Lake Kariba, Zambia

Where natural resources are a key component of the rural economy, the ability of the poor to realize their visions for the future depends significantly on institutional structures that govern resource access and management. This case study reports on an initiative on the shores of Lake Kariba in Zambia, where lakeshore residents face competition over fishing, tourism, and commercial aquaculture. Multistakeholder dialogue produced agreements with investors and increased accountability of state agencies and traditional leaders, enabling communities to have greater influence over their futures through improvements in aquatic resource governance. The report documents the rationale for the approach followed and steps in the capacity-building process, discusses obstacles encountered, and identifies lessons for policymakers and practitioners seeking to implement a similar approach

Molecular transport junctions: Current from electronic excitations in the leads

Using a model comprising a 2-level bridge connecting free electron reservoirs we show that coupling of a molecular bridge to electron-hole excitations in the leads can markedly effect the source-drain current through a molecular junction.In some cases, e.g. molecules that exhibit strong charge transfer transitions, the contribution from electron-hole excitations can exceed the Landauer elastic current and dominate the observed conduction.Comment: 4 pages, 2 figures, submitted to PR

Increased Perceived Stress is Associated with Blunted Hedonic Capacity: Potential Implications for Depression Research

Preclinical studies suggest that stress exerts depressogenic effects by impairing hedonic capacity, in humans, however, the precise mechanisms linking stress and depression are largely unknown. As an initial step towards better understanding the association between stress and anhedonia, the present study tested, in two independent samples, whether individuals reporting elevated stress exhibit decreased hedonic capacity. The Perceived Stress Scale (PSS) measured the decree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Hedonic capacity was objectively assessed using a signal-detection task based on a differential reinforcement schedule. Decreased reward responsiveness (i.e., the participants propensity to modulate behavior as a function of reward) was used as an operational measure of hedonic capacity. In both Study 1 (n = 88) and Study 2 (n = 80), participants with high PSS scores displayed blunted reward responsiveness and reported elevated anhedonic symptoms. Additionally, PSS scores predicted reduced reward responsiveness even after controlling for general distress and anxiety symptoms. These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression.Psycholog

Increased Perceived Stress is Associated with Blunted Hedonic Capacity: Potential Implications for Depression Research

Preclinical studies suggest that stress exerts depressogenic effects by impairing hedonic capacity, in humans, however, the precise mechanisms linking stress and depression are largely unknown. As an initial step towards better understanding the association between stress and anhedonia, the present study tested, in two independent samples, whether individuals reporting elevated stress exhibit decreased hedonic capacity. The Perceived Stress Scale (PSS) measured the decree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Hedonic capacity was objectively assessed using a signal-detection task based on a differential reinforcement schedule. Decreased reward responsiveness (i.e., the participants propensity to modulate behavior as a function of reward) was used as an operational measure of hedonic capacity. In both Study 1 (n = 88) and Study 2 (n = 80), participants with high PSS scores displayed blunted reward responsiveness and reported elevated anhedonic symptoms. Additionally, PSS scores predicted reduced reward responsiveness even after controlling for general distress and anxiety symptoms. These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression.Psycholog