65 research outputs found

    Clamp loader ATPases and the evolution of DNA replication machinery

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    Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life

    Spike-Based Bayesian-Hebbian Learning of Temporal Sequences

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    Many cognitive and motor functions are enabled by the temporal representation and processing of stimuli, but it remains an open issue how neocortical microcircuits can reliably encode and replay such sequences of information. To better understand this, a modular attractor memory network is proposed in which meta-stable sequential attractor transitions are learned through changes to synaptic weights and intrinsic excitabilities via the spike-based Bayesian Confidence Propagation Neural Network (BCPNN) learning rule. We find that the formation of distributed memories, embodied by increased periods of firing in pools of excitatory neurons, together with asymmetrical associations between these distinct network states, can be acquired through plasticity. The model's feasibility is demonstrated using simulations of adaptive exponential integrate-and-fire model neurons (AdEx). We show that the learning and speed of sequence replay depends on a confluence of biophysically relevant parameters including stimulus duration, level of background noise, ratio of synaptic currents, and strengths of short-term depression and adaptation. Moreover, sequence elements are shown to flexibly participate multiple times in the sequence, suggesting that spiking attractor networks of this type can support an efficient combinatorial code. The model provides a principled approach towards understanding how multiple interacting plasticity mechanisms can coordinate hetero-associative learning in unison

    Protein Homeostasis, Aging and Alzheimer’s Disease

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    System and Method for Underwater Radiography

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    A system for subsea imaging comprises a first plate having an inner surface, an outer surface, and a cavity formed in the inner surface. In addition, the system comprises a phosphor imaging plate disposed in the cavity. Further, the system comprises a second plate having an inner surface facing the inner surface of the first plate and an outer surface facing away from the outer surface of the first plate. Still further, the system comprises a seal member disposed between the inner surface of the first plate and the inner surface of the second plate. The seal member extends around the perimeter of the cavity and is configured to seal the phosphor imaging plate and the cavity from intrusion water

    AFLPs support deep relationships among darters (Percidae: Etheostomatinae) consistent with morphological hypotheses

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    Recent attention has focused on the efficacy of amplified fragment length polymorphisms (AFLPs) for resolving deep evolutionary relationships. Here we show that AFLPs provide resolution of deep relationships within the family Percidae that are more consistent with previous morphological hypotheses than are relationships proposed by previous molecular analyses. Despite in silico predictions, we were able to resolve relatively ancient divergences, estimated at >25 MA. We show that the most distantly related species share the fewest fragments, but suggest that large data sets and extensive taxon sampling are sufficient to overcome this obstacle of the AFLP technique for deep divergences. We compare genetic distances estimated from mitochondrial DNA with those from AFLPs and contrast traditional PAUP(*) Nei–Li AFLP genetic distances with a recently proposed method utilizing the Dice equation with constraining nucleotides
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