Cargo Transport: Two Motors Are Sometimes Better Than One

Molecular motor proteins are crucial for the proper distribution of organelles and vesicles in cells. Much of our current understanding of how motors function stems from studies of single motors moving cargos in vitro. More recently, however, there has been mounting evidence that the cooperation of multiple motors in moving cargos and the regulation of motor–filament affinity could be key mechanisms that cells utilize to regulate cargo transport. Here, we review these recent advances and present a picture of how the different mechanisms of regulating the number of motors moving a cargo could facilitate cellular functions

Cargo Transport at Microtubule Crossings: Evidence for Prolonged Tug-of-War between Kinesin Motors

AbstractIntracellular transport of cargos along microtubules is often complicated by the topology of the underlying filament network. The fundamental building blocks for this complex arrangement are filament intersections. The navigation of cargos across microtubule intersections remains poorly understood. Here, we demonstrate that kinesin-driven cargos are engaged in a tug-of-war at microtubule intersections. Tug-of-war events result in long pauses that can last from a few seconds to several minutes. We demonstrate that the extent of the tug-of-war and the duration of pauses change with the number of motors on the cargo and can be regulated by ionic strength. We also show that dwell times at intersections depend on the angle between crossing microtubules. Our data suggest that local microtubule geometry can regulate microtubule-based transport

Local Ordering in the Pseudogap State of the High-Tc_c Superconductor Bi2_2Sr2_2CaCu2_2O8+δ_{8+\delta}

We report atomic scale characterization of the pseudogap state in a high-T$_c$ superconductor, Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$. The electronic states at low energies within the pseudogap exhibit spatial modulations having an energy-independent incommensurate periodicity. These patterns, which are oriented along the copper-oxygen bond directions, appear to be a consequence of an electronic ordering phenomenon--the observation of which correlates with the pseudogap in the density of electronic states. Our results provide a stringent test for various ordering scenarios in the cuprates, which have been central in the debate on the nature of the pseudogap and the complex electronic phase diagram of these compounds.Comment: To appear on Science Express, http://www.sciencemag.org/sciencexpress/recent.shtml, 19 pages, 4 figures, pdf onl

Thyristor-Bypassed Sub-Module Power-Groups for Achieving High-Efficiency, DC Fault Tolerant Multilevel VSCs

Achieving DC fault tolerance in modular multilevel converters requires the use of a significant number of Sub-Modules (SMs) which are capable of generating a negative voltage. This results in an increase in the number of semiconductor devices in the current path, increasing converter conduction losses. This paper introduces a thyristor augmented multilevel structure called a Power-Group (PG), which replaces the stacks of SMs in modular converters. Each PG is formed out of a series stack of SMs with a parallel force-commutated thyristor branch, which is used during normal operation as a low loss bypass path in order to achieve significant reduction in overall losses. The PG also offers negative voltage capability and so can be used to construct high efficiency DC fault tolerant converters. Methods of achieving the turn-on and turn-off of the thyristors by using voltages generated by the parallel stack of SMs within each PG are presented, while keeping both the required size of the commutation inductor, and the thyristor turn-off losses low. Efficiency estimates indicate that this concept could result in converter topologies with power-losses as low as 0.3% rated power, whilst retaining high quality current waveforms and achieving tolerance to both AC and DC faults

High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport

High-resolution particle tracking shows a specific role for the dynein regulatory factor LIS1 in high-load axonal transport of large vesicles but no evidence for mechanical activation of opposite-directed motors

The genetic diversity and evolution of field pea (Pisum) studied by high throughput retrotransposon based insertion polymorphism (RBIP) marker analysis

BACKGROUND: The genetic diversity of crop species is the result of natural selection on the wild progenitor and human intervention by ancient and modern farmers and breeders. The genomes of modern cultivars, old cultivated landraces, ecotypes and wild relatives reflect the effects of these forces and provide insights into germplasm structural diversity, the geographical dimension to species diversity and the process of domestication of wild organisms. This issue is also of great practical importance for crop improvement because wild germplasm represents a rich potential source of useful under-exploited alleles or allele combinations. The aim of the present study was to analyse a major Pisum germplasm collection to gain a broad understanding of the diversity and evolution of Pisum and provide a new rational framework for designing germplasm core collections of the genus. RESULTS: 3020 Pisum germplasm samples from the John Innes Pisum germplasm collection were genotyped for 45 retrotransposon based insertion polymorphism (RBIP) markers by the Tagged Array Marker (TAM) method. The data set was stored in a purpose-built Germinate relational database and analysed by both principal coordinate analysis and a nested application of the Structure program which yielded substantially similar but complementary views of the diversity of the genus Pisum. Structure revealed three Groups (1-3) corresponding approximately to landrace, cultivar and wild Pisum respectively, which were resolved by nested Structure analysis into 14 Sub-Groups, many of which correlate with taxonomic sub-divisions of Pisum, domestication related phenotypic traits and/or restricted geographical locations. Genetic distances calculated between these Sub-Groups are broadly supported by principal coordinate analysis and these, together with the trait and geographical data, were used to infer a detailed model for the domestication of Pisum. CONCLUSIONS: These data provide a clear picture of the major distinct gene pools into which the genus Pisum is partitioned and their geographical distribution. The data strongly support the model of independent domestications for P. sativum ssp abyssinicum and P. sativum. The relationships between these two cultivated germplasms and the various sub-divisions of wild Pisum have been clarified and the most likely ancestral wild gene pools for domesticated P. sativum identified. Lastly, this study provides a framework for defining global Pisum germplasm which will be useful for designing core collections

Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

Thyristor/Diode-Bypassed Sub-Module Power-Groups for Improved Efficiency in Modular Multilevel Converters

The half-bridge Modular Multilevel Converter (MMC) is a Voltage Source Converter (VSC) with high effi- ciency, controllability and modularity. The topology is weak to DC side faults unless bipolar sub-modules are used, but this results in decreased efficiency. Power-Groups (PGs), a thyristor augmented multilevel structure, have been proposed as a way to reduce the power-loss increase arising from achieving DC- fault-tolerance. This paper investigates whether the PG concept can also achieve significant efficiency improvements in VSCs that are not required to be DC fault tolerant. A Single Sub-Module Voltage (SSMV) method of controlling the turn-on/turn-off of the thyristor assembly within each PG structure is presented and the differences with the previously detailed Dual Sub-Module Voltage (DSMV) technique are described. Two thyristor-based PG structures for use in non-DC-fault-tolerant MMCs are proposed, one using SSMV and the other using DSMV. A comparison is made considering the required semiconductor device count, the impact on thyristor snubber design, and the overall power- losses achieved. A further, simplified, variant using a diode bypassed PG structure is presented which results in power- loss reductions during rectifier mode only. Results show that power-loss reductions of ∼ 20-25% can be achieved by using the proposed PG structures to augment a half-bridge MMC

Independent, Rapid and Targeted Loss of Highly Repetitive DNA in Natural and Synthetic Allopolyploids of Nicotiana tabacum

Allopolyploidy (interspecific hybridisation and polyploidy) has played a significant role in the evolutionary history of angiosperms and can result in genomic, epigenetic and transcriptomic perturbations. We examine the immediate effects of allopolyploidy on repetitive DNA by comparing the genomes of synthetic and natural Nicotiana tabacum with diploid progenitors N. tomentosiformis (paternal progenitor) and N. sylvestris (maternal progenitor). Using next generation sequencing, a recently developed graph-based repeat identification pipeline, Southern blot and fluorescence in situ hybridisation (FISH) we characterise two highly repetitive DNA sequences (NicCL3 and NicCL7/30). Analysis of two independent high-throughput DNA sequencing datasets indicates NicCL3 forms 1.6–1.9% of the genome in N. tomentosiformis, sequences that occur in multiple, discontinuous tandem arrays scattered over several chromosomes. Abundance estimates, based on sequencing depth, indicate NicCL3 is almost absent in N. sylvestris and has been dramatically reduced in copy number in the allopolyploid N. tabacum. Surprisingly elimination of NicCL3 is repeated in some synthetic lines of N. tabacum in their forth generation. The retroelement NicCL7/30, which occurs interspersed with NicCL3, is also under-represented but to a much lesser degree, revealing targeted elimination of the latter. Analysis of paired-end sequencing data indicates the tandem component of NicCL3 has been preferentially removed in natural N. tabacum, increasing the proportion of the dispersed component. This occurs across multiple blocks of discontinuous repeats and based on the distribution of nucleotide similarity among NicCL3 units, was concurrent with rounds of sequence homogenisation