Calcium block of Na+ channels and its effect on closing rate

Calcium ion transiently blocks Na+ channels, and it shortens the time course for closing of their activation gates. We examined the relation between block and closing kinetics by using the Na+ channels natively expressed in GH3 cells, a clonal line of rat pituitary cells. To simplify analysis, inactivation of the Na+ channels was destroyed by including papain in the internal medium. All divalent cations tested, and trivalent La3+, blocked a progressively larger fraction of the channels as their concentration increased, and they accelerated the closing of the Na+ channel activation gate. For calcium, the most extensively studied cation, there is an approximately linear relation between the fraction of the channels that are calcium-blocked and the closing rate. Extrapolation of the data to very low calcium suggests that closing rate is near zero when there is no block. Analysis shows that, almost with certainty, the channels can close when occupied by calcium. The analysis further suggests that the channels close preferentially or exclusively from the calcium-blocked state.

Differential expression of major histocompatibility complex class II genes on murine macrophages associated with T cell cytokine profile and protective/suppressive effects

Protective/suppressive major histocompatibility complex (MHC) class II alleles have been identified in humans and mice where they exert a disease-protective and immunosuppressive effect. Various modes of action have been proposed, among them differential expression of MHC class II genes in different types of antigen-presenting cells impacting on the T helper type 1 (Th1)–Th2 balance. To test this possibility, the expression of H-2 molecules from the four haplotypes H-2b, H-2d, H-2k, and H-2q was determined on bone marrow-derived macrophages (BMDMs) and splenic B cells. The I-Ab and I-Ek molecules, both well characterized as protective/suppressive, are expressed at a high level on almost all CD11b+ BMDMs for 5–8 days, after which expression slowly declines. In contrast, I-Ad, I-Ak, and I-Aq expression is lower, peaks over a shorter period, and declines more rapidly. No differential expression could be detected on B cells. In addition, the differential MHC class II expression found on macrophages skews the cytokine response of T cells as shown by an in vitro restimulation assay with BMDMs as antigen-presenting cells. The results indicate that macrophages of the protective/suppressive haplotypes express MHC class II molecules at a high level and exert Th1 bias, whereas low-level expression favors a Th2 response. We suggest that the extent of expression of the class II gene gates the back signal from T cells and in this way controls the activity of macrophages. This effect mediated by polymorphic nonexon segments of MHC class II genes may play a role in determining disease susceptibility in humans and mice.

Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment

IA, JNP, and MP were partly supported by the NIH, grants R01-AI-100947 to MP, and R21-GM-107683 to Matthias Chung, subcontract to MP. JNP was partly supported by an NSF graduate fellowship number DGE750616. IA, JNP, BRL, OCS and MP were supported in part by the Bill and Melinda Gates Foundation, award number 42917 to OCS. JP and AWW received core funding support from The Wellcome Trust (grant number 098051). AWW, and the Rowett Institute of Nutrition and Health, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS).

Neuronal nicotinic threonine-for-leucine 247 α7 mutant receptors show different gating kinetics when activated by acetylcholine or by the noncompetitive agonist 5-hydroxytryptamine

Mutation of the highly conserved leucine residue (Leu-247) converts 5-hydroxytryptamine (5HT) from an antagonist into an agonist of neuronal homomeric α7 nicotinic acetylcholine receptor expressed in Xenopus oocytes. We show here that acetylcholine (AcCho) activates two classes of single channels with conductances of 44 pS and 58 pS, similar to those activated by 5HT. However, the mean open time of AcCho-gated ion channels (11 ms) is briefer than that of 5HT-gated ion channels (18 ms). Furthermore, whereas the open time of AcCho channels lengthens with hyperpolarization, that of 5HT channels is decreased. In voltage-clamped oocytes, the apparent affinity of the α7 mutant receptor for 5HT is not modified by the presence of dihydro-β-erythroidine, which acts on the AcCho binding site in a competitive manner. This indicates a noncompetitive action of 5HT on nicotinic acetylcholine receptors. Considered together, our findings show that AcCho gates α7 mutant channels with similar conductance but with different kinetic profile than the channels gated by 5HT, suggesting that the two agonists act on different docking sites. These results will help to understand the crosstalk between cholinergic and serotonergic systems in the central nervous system.

High frequency of sex and equal frequencies of mating types in natural populations of the ciliate Tetrahymena thermophila.

In ciliate protists, sex involves the temporary joining of two cells of compatible mating type, followed by meiosis and exchange of gametic nuclei between conjugants. Reproduction is by asexual binary fission following conjugation. For the many ciliates with fixed multiple mating types, frequency-dependent sex-ratio theory predicts equal frequencies of mating types, if sex is common in nature. Here, we report that in natural populations of Tetrahymena thermophila sexually immature cells, indicative of recent conjugation, are found from spring through fall. In addition, the seven mating types occur in approximately equal frequencies, and these frequencies appear to be maintained by interaction between complex, multiple mat alleles and environmental conditions during conjugation. Such genotype-environment interaction determining mating type frequency is rare among ciliates.

Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation.

Art influences on Mark Z. Danielewski's House of Leaves and Los Angeles's influence on Johnny Truant

"...is a novel that combines literature and art to create a unique postmodern object. It was published just over a decade ago, and in that time numerous scholars and students have written papers and articles on it. Within these articles, the themes are usually about deconstruction, the house as a digital object, the house's lack of homeliness, or characters who claim authorial presence. Danielewski distance himself from that role. The house and its impossible labyrinth are the central feature of the book. A house should provide stability, but this house shifts its rooms and walls at random. A house should protect its occupants, but this one kills people. This house links itself into an infinite amount of information through its use of the internet as an influence and a stylistic device, but it has nothing but an absence in its very foundation, an empty labyrinth with an unseen monster."

Rome, Italy, 1891 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Pianta di Roma, col patrocinio del comune di Roma. It was published by editore Loreto Pasqualucci [per] dall' Istituto cartografico italiano in 1891. Scale 1:6,000. Map in Italian.The image inside the map neatline is georeferenced to the surface of the earth and fit to the European Datum 1950, Universal Transverse Mercator (UTM) Zone 33N projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads and stations, drainage, built-up areas and selected buildings, walls, gates, fortification, ground cover, and more. Relief shown by shading. Includes also index and inset: Receniti di Roma nei successivi periodi della sua storia.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Jerusalem, 1876 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Ordnance survey of Jerusalem, by captain Charles W. Wilson R. F. under the direction of Colonel Sir Henry James, R.E., F.R.S., &c. director of the Ordnance Survey, 1864-5. It was published by Ordnance Survey Office in 1876. Rev. [of 1864-5 ed.]. Revised 1876. Scale 1:2,500. Covers primarily the Old City.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM Zone 36S, meters, WGS 1984) projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings (churches, synagogues, convents, schools), fortification, gates, religious sites, cemeteries, watch houses, cisterns, tombs, pools, aqueducts, and more. Relief shown by hachures, contours and spot heights. Includes also a list of references.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Rome, Italy, 1705 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Novissima et accuratissima delineatio Romae veteris et novae : in viatorum usum et commoditatem excusa, Petri Vander Aa. It was published by Petri Vander Aa in [1705]. Scale [ca. 1:20,040]. Covers Rome, Italy and Vatican City. Map in Latin and Italian.The image inside the map neatline is georeferenced to the surface of the earth and fit to the "European Datum 1950 UTM Zone 33N" coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map.This map shows features such as roads, drainage, built-up areas and selected buildings pictorially, walls, gates, fortification, ground cover, and more. Relief is shown by hachures. Includes indexes.This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Rome, Italy, 1715 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Urbis Romae veteris ac modernae accurata delineatio, edita a Ioh. Bapt. Homanno S.C.M. geographo Norimbergae. It was published by Joh. Bapt. Homannus in [1715]. Scale [ca. 1:20,040]. Covers Rome, Italy and Vatican City. Map in Latin and German.The image inside the map neatline is georeferenced to the surface of the earth and fit to the "European Datum 1950 UTM Zone 33N" coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map.This map shows features such as roads, drainage, built-up areas and selected buildings pictorially, walls, gates, fortification, ground cover, and more. Relief is shown by hachures. Includes text, index, and illustrations.This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Rome, Italy, 1755 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Vrbis Romae ichnographia, à Leonardo Bufalino ligneis formis evulgata atque aeri incisa à Ioh. Baptista Nolli, geometra et architecto summi Pontificus Benedicti XIV. It was published by Offic. Homann in 1755. Scale [ca. 1:5,000]. Covers Rome, Italy and Vatican City. Map in Latin.The image inside the map neatline is georeferenced to the surface of the earth and fit to the "European Datum 1950 UTM Zone 33N" coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map.This map shows features such as roads, drainage, built-up areas and selected buildings, walls, gates, fortification, and more. Relief is shown by hachures. Includes indexes.This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Rome, Italy, 1823 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Nuova pianta di Roma Moderna, estratta dalla grande del Nolli corretta ed accresciuta de nomi delle contrade indicati al loro rispettivo sito in Roma; Pietro Ruga incise. It was published by Venanzio Monaldini Libraio e Cartolaro in 1823. Scale [ca. 1:9,120]. Covers Rome, Italy and Vatican City. The image inside the map neatline is georeferenced to the surface of the earth and fit to the "European Datum 1950 UTM Zone 33N" coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, city districts, walls, gates, and fortifications, selected buildings, and more. Relief is shown by hachures. Includes index and inset plans: Pianta della Chiesa di S. Lorenzo fuori le mura -- Mausoleo di S. Costanza -- Pianta della Basilica di S. Paolo -- Pianta del Pantheon, degli avanzi delle Terme di Agrippa, e dé ruderi scoperti recentemente. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Rome, Italy, 1832 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Pianta della citta di Roma : con la indicazione di tvtte le antichita e nvovi abbellimenti nell anno MDCCCXXXII, Pietro Ruga incise. It was published by Venanzio Monaldini libraio e cartolaro in 1832. Scale [ca. 1:5,066]. Covers Rome, Italy and Vatican City.The image inside the map neatline is georeferenced to the surface of the earth and fit to the "European Datum 1950 UTM Zone 33N" coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, city districts, walls, gates, and fortifications, selected buildings, and more. Relief is shown by hachures. Includes indices and architectural engravings at left and right margins: Basilica di S. Giovanni -- Interno di S. Giovanni -- Basilica di S. Paolo -- Interno di S. Paolo -- Campidoglio Moderno -- Anfiteatro Favio -- Primaide di C. Cestio -- Foro Trajano -- Basilica di S. Pietro -- Interno di S. Pietro -- Basilica di S. M.a Maggiore -- Interno di S. M.a Maggiore -- Pantheon di Agrippa -- Interno del Pantheon -- Monte Cavallo -- Foro Romano. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.