Temporal integration by a slowly inactivating K+ current in hippocampal neurons

A central aspect of neuronal function is how each nerve cell translated synaptic input into a sequence of action potentials that carry information along the axon, coded as spike frequency. When transduction from a graded depolarizing input to spikes is studied by injecting a depolarizing current, there is often a remarkably long delay to the first action potential, both in mammalian and molluscan neurons. Here, I report that the delayed excitation in rat hippocampal neurons is due to a slowly inactivating potassium current, ID. ID co-exists with other voltage-gated K+ currents, including a fast A current and a slow delayed rectifier current. As ID activates in the subthreshold range, and takes tens of seconds to recover from inactivation, it enables the cell to integrate separate depolarizing inputs over long times. ID also makes the encoding properties of the cell exceedingly sensitive to the prevailing membrane potential.     

Nonlinear elasticity in biological gels

The mechanical properties of soft biological tissues are essential to their physiological function and cannot easily be duplicated by synthetic materials. Unlike simple polymer gels, many biological materials--including blood vessels, mesentery tissue, lung parenchyma, cornea and blood clots--stiffen as they are strained, thereby preventing large deformations that could threaten tissue integrity. The molecular structures and design principles responsible for this nonlinear elasticity are unknown. Here we report a molecular theory that accounts for strain-stiffening in a range of molecularly distinct gels formed from cytoskeletal and extracellular proteins and that reveals universal stress-strain relations at low to intermediate strains. The input to this theory is the force-extension curve for individual semi-flexible filaments and the assumptions that biological networks composed of these filaments are homogeneous, isotropic, and that they strain uniformly. This theory shows that systems of filamentous proteins arranged in an open crosslinked mesh invariably stiffen at low strains without requiring a specific architecture or multiple elements with different intrinsic stiffness.     

Protein phosphatase 1 is a molecular constraint on learning and memory

Repetition in learning is a prerequisite for the formation of accurate and long-lasting memory. Practice is most effective when widely distributed over time, rather than when closely spaced or massed. But even after efficient learning, most memories dissipate with time unless frequently used. The molecular mechanisms of these time-dependent constraints on learning and memory are unknown. Here we show that protein phosphatase 1 (PP1) determines the efficacy of learning and memory by limiting acquisition and favouring memory decline. When PP1 is genetically inhibited during learning, short intervals between training episodes are sufficient for optimal performance. The enhanced learning correlates with increased phosphorylation of cyclic AMP-dependent response element binding (CREB) protein, of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and of the GluR1 subunit of the AMPA receptor; it also correlates with CREB-dependent gene expression that, in control mice, occurs only with widely distributed training. Inhibition of PP1 prolongs memory when induced after learning, suggesting that PP1 also promotes forgetting. This property may account for ageing-related cognitive decay, as old mutant animals had preserved memory. Our findings emphasize the physiological importance of PP1 as a suppressor of learning and memory, and as a potential mediator of cognitive decline during ageing.     

Food habits of clouded salamanders ( Aneides ferreus ) in Curry County, Oregon (Amphibia: Caudata: Plethodontidae)

Stomach contents of 650 clouded salamanders ( Aneides ferreus ), collected monthly throughout the year from Curry County, Oregon, were examined. Samples from three age classes were involved: (1) 489 adults, (2) 131 juveniles, and (3) 30 hatchlings. Foods did not vary by sex, but did vary by age and by season. Hatchlings ate small items, particularly mites, springtails, flies, and small beetles. Juveniles fed mainly on flies, isopods (sowbugs), beetles, mites, and centipedes in winter; beetles, ants, and isopods in spring; ants and beetles in summer; and isopods, beetles, and ants in fall. Adults ate isopods and beetles as their major foods in winter, spring, and fall and isopods, ants, beetles, and earwigs in summer. Four species were exceedingly important as foods for these salamanders: an unidentified isopod, the snout beetle ( Trachyphloeus bifoveatus ), the European earwig ( Forficula auricularia ), and an ant ( Lasius alienus ).       

Gorenstein平坦预包络和预解式

我们在［７］中引进了Ｇｏｒｅｎｓｔｅｉｎ平坦模。本文将这类模的刻画推广到任意ｎ－Ｇｏｒｅｎｓｔｅｉｎ环上，并利用这类模刻画了ｎ－Ｇｏｒｅｓｔｅｉｎ环。而且，我们证明了任意ｎ－Ｇｏｒｅｎｓｔｅｉｎ环上Ｇｏｒｅｎｓｔｅｉｎ平坦预包络的存在性，并证得得这种环关于Ｇｏｒｅｎｓｔｅｉｎ平坦模的内射类的整体维数至多为ｎ－２，当ｎ≤１时，该整体维数为零。     

Birth of a relativistic outflow in the unusual γ-ray transient Swift J164449.3+573451

Active galactic nuclei, which are powered by long-term accretion onto central supermassive black holes, produce relativistic jets with lifetimes of at least one million years, and the observation of the birth of such a jet is therefore unlikely. Transient accretion onto a supermassive black hole, for example through the tidal disruption of a stray star, thus offers a rare opportunity to study the birth of a relativistic jet. On 25 March 2011, an unusual transient source (Swift J164449.3+573451) was found, potentially representing such an accretion event. Here we report observations spanning centimetre to millimetre wavelengths and covering the first month of evolution of a luminous radio transient associated with Swift J164449.3+573451. The radio transient coincides with the nucleus of an inactive galaxy. We conclude that we are seeing a newly formed relativistic outflow, launched by transient accretion onto a million-solar-mass black hole. A relativistic outflow is not predicted in this situation, but we show that the tidal disruption of a star naturally explains the observed high-energy properties and radio luminosity and the inferred rate of such events. The weaker beaming in the radio-frequency spectrum relative to γ-rays or X-rays suggests that radio searches may uncover similar events out to redshifts of z?≈?6.     

AAV serotype 2 vectors preferentially integrate into active genes in mice

Recombinant adeno-associated virus serotype 2 (rAAV2) is a promising vector for gene therapy because it can achieve long-term stable transgene expression in animals and human subjects after direct administration of vectors into various target tissues. In the liver, although stable transgene expression primarily results from extrachromosomal vector genomes, a series of experiments has shown that vector genomes integrate into host chromosomes in hepatocytes at a low frequency. Despite the low integration efficiency, recent reports of retroviral insertional mutagenesis in mice and two human subjects have raised concerns about the potential for rAAV2-mediated insertional mutagenesis. Here we characterize rAAV2-targeted chromosomal integration sites isolated from selected or non-selected hepatocytes in vector-injected mouse livers. We document frequent chromosomal deletions of up to 2 kb at integration sites (14 of 14 integrations, 100%; most of the deletions were <0.3 kb) and preferred integration into genes (21 of 29 integrations, 72%). In addition, all of the targeted genes analyzed (20 of 20 targeted genes, 100%) were expressed in the liver. This is the first report to our knowledge on host chromosomal effects of rAAV2 integration in animals, and it provides insights into the nature of rAAV2 vector integration into chromosomes in quiescent somatic cells in animals and human subjects.