Growth factor-mediated Fyn signaling regulates α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression in rodent neocortical neurons

Src-family protein tyrosine kinases (PTKs) transduce signals to regulate neuronal development and synaptic plasticity. However, the nature of their activators and molecular mechanisms underlying these neural processes are unknown. Here, we show that brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor enhance expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor 1 and 2/3 proteins in rodent neocortical neurons via the Src-family PTK(s). The increase in AMPA receptor levels was blocked in cultured neocortical neurons by addition of a Src-family-selective PTK inhibitor. Accordingly, neocortical cultures from Fyn-knockout mice failed to respond to BDNF whereas those from wild-type mice responded. Moreover, the neocortex of young Fyn mutants exhibited a significant in vivo reduction in these AMPA receptor proteins but not in their mRNA levels. In vitro kinase assay revealed that BDNF can indeed activate the Fyn kinase: It enhanced tyrosine phosphorylation of Fyn as well as that of enolase supplemented exogenously. All of these results suggest that the Src-family kinase Fyn, activated by the growth factors, plays a crucial role in modulating AMPA receptor expression during brain development.

Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex

Cortical blood flow at the level of individual capillaries and the coupling of neuronal activity to flow in capillaries are fundamental aspects of homeostasis in the normal and the diseased brain. To probe the dynamics of blood flow at this level, we used two-photon laser scanning microscopy to image the motion of red blood cells (RBCs) in individual capillaries that lie as far as 600 μm below the pia mater of primary somatosensory cortex in rat; this depth encompassed the cortical layers with the highest density of neurons and capillaries. We observed that the flow was quite variable and exhibited temporal fluctuations around 0.1 Hz, as well as prolonged stalls and occasional reversals of direction. On average, the speed and flux (cells per unit time) of RBCs covaried linearly at low values of flux, with a linear density of ≈70 cells per mm, followed by a tendency for the speed to plateau at high values of flux. Thus, both the average velocity and density of RBCs are greater at high values of flux than at low values. Time-locked changes in flow, localized to the appropriate anatomical region of somatosensory cortex, were observed in response to stimulation of either multiple vibrissae or the hindlimb. Although we were able to detect stimulus-induced changes in the flux and speed of RBCs in some single trials, the amplitude of the stimulus-evoked changes in flow were largely masked by basal fluctuations. On average, the flux and the speed of RBCs increased transiently on stimulation, although the linear density of RBCs decreased slightly. These findings are consistent with a stimulus-induced decrease in capillary resistance to flow.

Intracellular polyamines mediate inward rectification of Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that lack the glutamate receptor GluR2 subunit are Ca(2+)-permeable and exhibit inwardly rectifying current responses to kainate and AMPA. A proportion of cultured rat hippocampal neurons show similar Ca(2+)-permeable inwardly rectifying AMPA receptor currents. Inward rectification in these neurons was lost with intracellular dialysis and was not present in excised outside-out patches but was maintained in perforated-patch whole-cell recordings, suggesting that a diffusible cytoplasmic factor may be responsible for rectification. Inclusion of the naturally occurring polyamines spermine and spermidine in the recording pipette prevented loss of rectification in both whole-cell and excised-patch recordings; Mg2+ and putrescine were without effect. Inward rectification of Ca(2+)-permeable AMPA receptors may reflect voltage-dependent channel block by intracellular polyamines.

Windham County, Connecticut, 1856 (Image 2 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Windham County, Connecticut, from actual survey by E.P. Gerrish, W.C. Eaton & D.S. & H.C. Osborn, 1855; lith by W.H. Rease. It was published by E.M. Woodford in 1856. Scale [ca. 1:42,240]. This layer is image 2 of 4 total images, representing the southeast portion of the four sheet source map.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Connecticut State Plane coordinate system (NAD 1983 in Feet) (Fipszone 0600). 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, drainage, public buildings, schools, churches, cemeteries, industry locations (e.g. mills, factories, mines, etc.), private buildings with names of property owners, town boundaries, and more. Relief shown by hachures. It includes many cadastral insets of individual county towns and villages. It also includes illustrations, business directories, and tables of statistics and distances.This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.

Warsaw, Poland, 1762 (Image 2 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de la ville de Varsovie : dedie A. S. Mavgvste III roi de Pologne Electevr de Saxe, levé par ordre de S.E. M. le Comte Bielinksi Grand Marechal de la Covronne par M. P. Ricavd de Tirregaille Lieut. Colonel et Inginieur au Service du Roi et de la Repvblique en 1762 ; Marstalski fecit. It was published in 1762. Scale [ca. 1:6,600]. Covers Warsaw, Poland. This layer is image 2 of 4 total images, representing the northwest portion of the four sheet source map. Map in French and Polish. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Pulkovo 1942 Adjust 1958 Poland Zone II' 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, fortification, ground cover, and more. Relief shown by hachures. Includes index and views. 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.

Inhibition of NF-kB activation and cytokines production in THP-1 monocytes by 2-styrylchromones

Nuclear factor kappa B (NF-kB) is one of the most important transcription factors whose modulation triggers a cascade of signaling events, namely the expression of many cytokines, enzymes, chemokines, and adhesion molecules, some of which being potential key targets for intervention in the treatment of inflammatory conditions. The 2-styrylchromones (2-SC) designation represents a well-recognized group of natural and synthetic chromones, vinylogues of flavones (2-phenylchromones). Several 2-SC were recently tested for their anti-inflammatory potential, regarding the arachidonic acid metabolic cascade, showing some motivating results. In addition, several flavones with structural similarities to 2-SC have shown NF-kB inhibitory properties. Hence, the aim of the present work was to continue the investigation on the interference of 2-SC in inflammatory pathways. Herein we report their effects on lipopolysaccharide (LPS)-induced NF-kB activation and consequent production of proinflammatory cytokines/chemokine, using a human monocytic cell line (THP-1). From the twelve 2-SC tested, three of them were able to significantly inhibit the NF-kB activation and to reduce the production of the proinflammatory cytokines/chemokine. The compound 3',4',5-trihydroxy-2- styrylchromone stood up as the most active in both assays, being a promising candidate for an anti-inflammatory drug.

Abundance of ostracoda in sediment cores CRP-1 and CRP-2

Sparse, poorly preserved late Oligocene (3 species) and early Miocene (4 species) ostracod faunas have been recovered from CRP-2A, while relatively more abundant Quaternary faunas occur in CRP-1 (24 species). All taxa are marine. No definitive age assignments can be made on the two older faunas, which are not considered to be in situ, although the taxa identified are not at variance with sediment ages determined on other grounds. The Oligocene ostracods (Lithostratigraphical Unit, LSU 9.4) suggest deposition in cold, relatively shallow, shelf waters with faunal connections to the Antarctic Peninsula and South America, while the Miocene fauna (LSU 5.1) is considered to be a cool-cold, deeper water (?outer shelf) association with faunal connections to both New Zealand and the Antarctic Peninsula. The Quaternary faunas are primarily from LSU 3.1 (carbonate-rich layer), and suggest deposition in very cold, relatively quiet water that was at least 100 m, and possibly 130-200 m deep. None of the taxa are known from pre-Pleistocene sediments, and all occur in modern Antarctic/sub-Antarctic regimes, predominantly from south of 60° S. Specimens in the "carbonate-rich layer" probably have suffered minor penecontemporaneous fractionation, while the fauna in LSU 2.2 has suffered more extensive post-mortem transportation and possible reworking (though not necessarily from pre-Quaternary sources).