The Pusher as an Object of the Simulation Model in the Tasks of Studying Cyclic Mechanisms Dynamics

The cyclic mechanism is one of the basic automatic machines components. It is the cyclic mechanisms that define the performance and reliability limits of these machines. The methods for assessing the automatic machines reliability are based on data of dynamic forces acting on the mechanism's links, leading to their deformation and possible destruction under certain operating conditions. Simulation modeling of dynamic processes in cyclic mechanisms is based on its representation in the form of interconnected typical objects, the allowable properties and limits of which are known. The article presents the dynamics study results one of the basic high-speed automatic machines mechanism in the object-oriented representation. Mechanism performs translational motion and allows the possibility of one-way kinematic connection breaking.

Molecular architecture of black widow spider neurotoxins

Latrotoxins (LaTXs) are presynaptic pore-forming neurotoxins found in the venom of Latrodectus spiders. The venom contains a toxic cocktail of seven LaTXs, with one of them targeting vertebrates (α-latrotoxin (α-LTX)), five specialized on insects (α, β, γ, δ, ε- latroinsectotoxins (LITs), and one on crustaceans (α-latrocrustatoxin (α-LCT)). LaTXs bind to specific receptors on the surface of neuronal cells, inducing the release of neurotransmitters either by directly stimulating exocytosis or by forming Ca2+-conductive tetrameric pores in the membrane. Despite extensive studies in the past decades, a high-resolution structure of a LaTX is not yet available and the precise mechanism of LaTX action remains unclear. Here, we report cryoEM structures of the α-LCT monomer and the δ-LIT dimer. The structures reveal that LaTXs are organized in four domains. A C-terminal domain of ankyrin-like repeats shields a central membrane insertion domain of six parallel α-helices. Both domains are flexibly linked via an N-terminal α-helical domain and a small β-sheet domain. A comparison between the structures suggests that oligomerization involves major conformational changes in LaTXs with longer C-terminal domains. Based on our data we propose a cyclic mechanism of oligomerization, taking place prior membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca2+ ions and allow calcium flux at negative membrane potentials. Our comparative analysis between α-LCT and δ-LIT provides first crucial insights towards understanding the molecular mechanism of the LaTX family.

Molecular architecture of black widow spider neurotoxins

Latrotoxins (LaTXs) are presynaptic pore-forming neurotoxins found in the venom of Latrodectus spiders. The venom contains a toxic cocktail of seven LaTXs, with one of them targeting vertebrates (α-latrotoxin (α-LTX)), five specialized on insects (α, β, γ, δ, ɛ-latroinsectotoxins (LITs), and one on crustaceans (α-latrocrustatoxin (α-LCT)). LaTXs bind to specific receptors on the surface of neuronal cells, inducing the release of neurotransmitters either by directly stimulating exocytosis or by forming Ca2+-conductive tetrameric pores in the membrane. Despite extensive studies in the past decades, a high-resolution structure of a LaTX is not yet available and the precise mechanism of LaTX action remains unclear.Here, we report cryoEM structures of the α-LCT monomer and the δ-LIT dimer. The structures reveal that LaTXs are organized in four domains. A C-terminal domain of ankyrin-like repeats shields a central membrane insertion domain of six parallel α-helices. Both domains are flexibly linked via an N-terminal α-helical domain and a small β-sheet domain. A comparison between the structures suggests that oligomerization involves major conformational changes in LaTXs with longer C-terminal domains. Based on our data we propose a cyclic mechanism of oligomerization, taking place prior membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca2+ ions and allow calcium flux at negative membrane potentials. Our comparative analysis between α-LCT and δ-LIT provides first crucial insights towards understanding the molecular mechanism of the LaTX family.

Exploring cyclic networks of multisite modification reveals origins of information processing characteristics

Multisite phosphorylation (and generally multisite modification) is a basic way of encoding substrate function and circuits/networks of post-translational modifications (PTM) are ubiquitous in cell signalling. The information processing characteristics of PTM systems are a focal point of broad interest. The ordering of modifications is a key aspect of multisite modification, and a broad synthesis of the impact of ordering of modifications is still missing. We focus on a basic class of multisite modification circuits: the cyclic mechanism, which corresponds to the same ordering of phosphorylation and dephosphorylation, and examine multiple variants involving common/separate kinases and common/separate phosphatases. This is of interest both because it is encountered in concrete cellular contexts, and because it serves as a bridge between ordered (sequential) mechanisms (representing one type of ordering) and random mechanisms (which have no ordering). We show that bistability and biphasic dose response curves of the maximally modified phosphoform are ruled out for basic structural reasons independent of parameters, while oscillations can result with even just one shared enzyme. We then examine the effect of relaxing some basic assumptions about the ordering of modification. We show computationally and analytically how bistability, biphasic responses and oscillations can be generated by minimal augmentations to the cyclic mechanism even when these augmentations involved reactions operating in the unsaturated limit. All in all, using this approach we demonstrate (1) how the cyclic mechanism (with single augmentations) represents a modification circuit using minimal ingredients (in terms of shared enzymes and sequestration of enzymes) to generate bistability and oscillations, when compared to other mechanisms, (2) new design principles for rationally designing PTM systems for a variety of behaviour, (3) a basis and a necessary step for understanding the origins and robustness of behaviour observed in basic multisite modification systems.

Synthesis and Characterization of Copper Oxide Composite and Study of Composite Mediated Photo-Oxidative Degradation of Methylene Blue under Visible Light

Copper oxide composite was prepared from copper (II) acetate. Characterization of composite was performed by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), FT-IR Spectroscopy and X-ray diffractometry. According to the findings of SEM the particle size was within the range from 450 nm to 550 nm. Band gap energy was determined by reflectance measurement and value was found to be 4.21 eV. From the result of EDS, it appears that the composite contains only Cu and O atoms. Result of XRD confirms that the composite contains CuO, Cu2O and metallic Cu. FTIR spectrum of composite supports the presence of Cu2O. Adsorptive and catalytic properties of composite were studied using Methylene blue as adsorbent. Photo-oxidative degradation of MB was investigated in the suspension of composite in separate experiments at different pH ranging from 2.5 to 5.5 under visible light. Low pH range from 2.5 to 3.5 is most effective for degradation. This was explained by proposing a cyclic mechanism which suggests the conversion of Cu22+ to Cu2+ and vice versa. 95.5% of MB was found to degrade when 5×10-5 M solution of MB was irradiated for three hours in 100 mL suspension of composite having concentration 1gL-1 at pH 2.5.

The dynamics of cultivation and floods in arable lands of Central Argentina

Although floods in watersheds have been associated with land-use change since ancient times, the dynamics of flooding is still incompletely understood. In this paper we explored the relations between rainfall, groundwater level, and cultivation to explain the dynamics of floods in the extremely flat and valuable arable lands of the Quinto river watershed, in central Argentina. The analysis involved an area of 12.4 million hectare during a 26-year period (1978–2003), which comprised two extensive flooding episodes in 1983–1988 and 1996–2003. Supported by information from surveys as well as field and remote sensing measurements, we explored the correlation among precipitation, groundwater levels, flooded area and land use. Flood extension was associated to the dynamics of groundwater level. While no correlation with rainfall was recorded in lowlands, a significant correlation (P<0.01) between groundwater and rainfall in highlands was found when estimations comprise a time lag of one year. Correlations between groundwater level and flood extension were positive in all cases, but while highly significant relations (P<0.01) were found in highlands, non significant relations (P>0.05) predominate in lowlands. Our analysis supports the existence of a cyclic mechanism driven by the reciprocal influence between cultivation and groundwater in highlands. This cycle would involve the following stages: (a) cultivation boosts the elevation of groundwater levels through decreased evapotranspiration; (b) as groundwater level rises, floods spread causing a decline of land cultivation; (c) flooding propitiates higher evapotranspiration favouring its own retraction; (d) cultivation expands again following the retreat of floods. Thus, cultivation would trigger a destabilizing feedback self affecting future cultivation in the highlands. It is unlikely that such sequence can work in lowlands. The results suggest that rather than responding directly and solely to the same mechanism, floods in lowlands may be the combined result of various factors like local rainfall, groundwater level fluctuations, surface and subsurface lateral flow, and water-body interlinking. Although the hypothetical mechanisms proposed here require additional understanding efforts, they suggest a promising avenue of environmental management in which cultivation could be steered in the region to smooth the undesirable impacts of floods.