Directional instability of microtubule transport in the presence of kinesin and dynein, two opposite polarity motor proteins.

Kinesin and dynein are motor proteins that move in opposite directions along microtubules. In this study, we examine the consequences of having kinesin and dynein (ciliary outer arm or cytoplasmic) bound to glass surfaces interacting with the same microtubule in vitro. Although one might expect a balance of opposing forces to produce little or no net movement, we find instead that microtubules move unidirectionally for several microns (corresponding to hundreds of ATPase cycles by a motor) but continually switch between kinesin-directed and dynein-directed transport. The velocities in the plus-end (0.2-0.3 microns/s) and minus-end (3.5-4 microns/s) directions were approximately half those produced by kinesin (0.5 microns/s) and ciliary dynein (6.7 microns/s) alone, indicating that the motors not contributing to movement can interact with and impose a drag upon the microtubule. By comparing two dyneins with different duty ratios (percentage of time spent in a strongly bound state during the ATPase cycle) and varying the nucleotide conditions, we show that the microtubule attachment times of the two opposing motors as well as their relative numbers determine which motor predominates in this assay. Together, these findings are consistent with a model in which kinesin-induced movement of a microtubule induces a negative strain in attached dyneins which causes them to dissociate before entering a force-generating state (and vice versa); reversals in the direction of transport may require the temporary dissociation of the transporting motor from the microtubule. The bidirectional movements described here are also remarkably similar to the back-and-forth movements of chromosomes during mitosis and membrane vesicles in fibroblasts. These results suggest that the underlying mechanical properties of motor proteins, at least in part, may be responsible for reversals in microtubule-based transport observed in cells

I feel wealthy: a major determinant of Portuguese households’ indebtedness?

This paper examines the response of household debt to households’ perception of house prices using data from the first wave of the Household Finance and Consumption Survey. Whereas the literature has hitherto emphasized the effects of housing wealth on consumption, this study concentrates on the effects on debt accumulation—distinguishing mortgage debt from non-mortgage debt and inspecting over-indebtedness. Different measures of housing wealth are considered, controlling for tenure years. The findings reveal that the effects of housing wealth differ by type of loans and with the measure of housing wealth. Over-indebtedness is driven by the same factors that determine mortgage debt, suggesting a strong association between having outstanding liabilities from the primary residence and the risk of entering into default. Further estimations by different income and wealth classes revealed dissimilar housing wealth effects, with non-mortgage debt tending to rise among lower-income households and over-indebtedness tending to be larger among the wealthier.info:eu-repo/semantics/acceptedVersio

The Critical Tradition at Rhodes University: Retrospect and Prospect

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The many faces of LINER-like galaxies: a WISE view

We use the SDSS and WISE surveys to investigate the real nature of galaxies defined as LINERs in the BPT diagram. After establishing a mid-infrared colour W2-W3 = 2.5 as the optimal separator between galaxies with and without star formation, we investigate the loci of different galaxy classes in the W_{Ha} versus W2-W3 space. We find that: (1) A large fraction of LINER-like galaxies are emission-line retired galaxies, i.e galaxies which have stopped forming stars and are powered by hot low-mass evolved stars (HOLMES). Their W2-W3 colours show no sign of star formation and their Ha equivalent widths, W_{Ha}, are consistent with ionization by their old stellar populations. (2) Another important fraction have W2-W3 indicative of star formation. This includes objects located in the supposedly `pure AGN' zone of the BPT diagram. (3) A smaller fraction of LINER-like galaxies have no trace of star formation from W2-W3 and a high W_{Ha}, pointing to the presence of an AGN. (4) Finally, a few LINERs tagged as retired by their W_{Ha} but with W2-W3 values indicative of star formation are late-type galaxies whose SDSS spectra cover only the old `retired' bulge. This reinforces the view that LINER-like galaxies are a mixed bag of objects involving different physical phenomena and observational effects thrusted into the same locus of the BPT diagram.Comment: Accepted for publication in MNRAS; 9 pages, 6 figure

Killing them softly:managing pathogen polymorphism and virulence in spatially variable environments

Understanding why pathogen populations are genetically variable is vital because genetic variation fuels evolution, which often hampers disease control efforts. Here I argue that classical models of evolution in spatially variable environments – specifically, models of hard and soft selection – provide a useful framework to understand the maintenance of pathogen polymorphism and the evolution of virulence. First, the similarities between models of hard and soft selection and pathogen life cycles are described, highlighting how the type and timing of pathogen control measures impose density regulation that may affect both the level of pathogen polymorphism and virulence. The article concludes with an outline of potential lines of future theoretical and experimental work

Nucleotide specificity of the enzymatic and motile activities of dynein, kinesin, and heavy meromyosin.

The substrate specificities of dynein, kinesin, and myosin substrate turnover activity and cytoskeletal filament-driven translocation were examined using 15 ATP analogues. The dyneins were more selective in their substrate utilization than bovine brain kinesin or muscle heavy meromyosin, and even different types of dyneins, such as 14S and 22S dynein from Tetrahymena cilia and the beta-heavy chain-containing particle from the outer-arm dynein of sea urchin flagella, could be distinguished by their substrate specificities. Although bovine brain kinesin and muscle heavy meromyosin both exhibited broad substrate specificities, kinesin-induced microtubule translocation varied over a 50-fold range in speed among the various substrates, whereas heavy meromyosin-induced actin translocation varied only by fourfold. With both kinesin and heavy meromyosin, the relative velocities of filament translocation did not correlate well with the relative filament-activated substrate turnover rates. Furthermore, some ATP analogues that did not support the filament translocation exhibited filament-activated substrate turnover rates. Filament-activated substrate turnover and power production, therefore, appear to become uncoupled with certain substrates. In conclusion, the substrate specificities and coupling to motility are distinct for different types of molecular motor proteins. Such nucleotide "fingerprints" of enzymatic activities of motor proteins may prove useful as a tool for identifying what type of motor is involved in powering a motility-related event that can be reconstituted in vitro

Cloning and expression of a human kinesin heavy chain gene: interaction of the COOH-terminal domain with cytoplasmic microtubules in transfected CV-1 cells.

To understand the interactions between the microtubule-based motor protein kinesin and intracellular components, we have expressed the kinesin heavy chain and its different domains in CV-1 monkey kidney epithelial cells and examined their distributions by immunofluorescence microscopy. For this study, we cloned and sequenced cDNAs encoding a kinesin heavy chain from a human placental library. The human kinesin heavy chain exhibits a high level of sequence identity to the previously cloned invertebrate kinesin heavy chains; homologies between the COOH-terminal domain of human and invertebrate kinesins and the nonmotor domain of the Aspergillus kinesin-like protein bimC were also found. The gene encoding the human kinesin heavy chain also contains a small upstream open reading frame in a G-C rich 5' untranslated region, features that are associated with translational regulation in certain mRNAs. After transient expression in CV-1 cells, the kinesin heavy chain showed both a diffuse distribution and a filamentous staining pattern that coaligned with microtubules but not vimentin intermediate filaments. Altering the number and distribution of microtubules with taxol or nocodazole produced corresponding changes in the localization of the expressed kinesin heavy chain. The expressed NH2-terminal motor and the COOH-terminal tail domains, but not the alpha-helical coiled coil rod domain, also colocalized with microtubules. The finding that both the kinesin motor and tail domains can interact with cytoplasmic microtubules raises the possibility that kinesin could crossbridge and induce sliding between microtubules under certain circumstances

Substitutability between drugs, innovation, and fiscal policy in the pharmaceutical industry

A theoretical model is developed in order to examine and explain the growth and welfare effects of fiscal policies in the pharmaceutical industry. When the fiscal instrument is a tax over pharmaceutical firms' profits, R&D by firms in the pharmaceutical sector results in growth if there is a generic market. Otherwise, a subsidy over pharmaceutical firms' profits should be considered to generate innovation in medicines. In terms of policy implications, our empirical results suggest that stimulating generic competition in the pharmaceutical sector is a main instrument to contain costs and promote welfare.info:eu-repo/semantics/publishedVersio

Effect of hierarchical parish system on Portuguese housing rents

This manuscript analyzes an inter-parish housing rents gradient with respect to surrounding parishes. Using data on housing rents for 4049 Portuguese parishes in 278 municipalities, the paper explores the spatial patterns of housing rents using the geographically weighted regression (GWR) methodology. The housing rents can be explained by socio-economic factors comprising the effects of unemployment, sustainability, social diversity, elderly dependency, and population density. The proportion of overcrowded dwellings reflecting how poor living conditions affect housing rents was also included in the spatial analysis. On the structural side, characteristics of the dwellings were also included such as the area of the home and the number of other homes available in the parishes. Locational factors reflect households’ valuation for access to other parishes. In order to capture location characteristics, besides considering mobility within municipalities, the GWR allowed using distances to nearby parishes, i.e., parish hierarchy distance effect. The results suggest that the Portuguese rental housing market exhibits a heterogeneous pattern across the territory, displaying spatial variability and a hierarchical space pattern as a consequence of its locational attributes.info:eu-repo/semantics/publishedVersio