The EphA4 receptor regulates dendritic spine remodeling by affecting β1-integrin signaling pathways

Remodeling of dendritic spines is believed to modulate the function of excitatory synapses. We previously reported that the EphA4 receptor tyrosine kinase regulates spine morphology in hippocampal pyramidal neurons, but the signaling pathways involved were not characterized (Murai, K.K., L.N. Nguyen, F. Irie, Y. Yamaguchi, and E.B. Pasquale. 2003. Nat. Neurosci. 6:153–160). In this study, we show that EphA4 activation by ephrin-A3 in hippocampal slices inhibits integrin downstream signaling pathways. EphA4 activation decreases tyrosine phosphorylation of the scaffolding protein Crk-associated substrate (Cas) and the tyrosine kinases focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) and also reduces the association of Cas with the Src family kinase Fyn and the adaptor Crk. Consistent with this, EphA4 inhibits β1-integrin activity in neuronal cells. Supporting a functional role for β1 integrin and Cas inactivation downstream of EphA4, the inhibition of integrin or Cas function induces spine morphological changes similar to those associated with EphA4 activation. Furthermore, preventing β1-integrin inactivation blocks the effects of EphA4 on spines. Our results support a model in which EphA4 interferes with integrin signaling pathways that stabilize dendritic spines, thus modulating synaptic interactions with the extracellular environment

Sensitivity of simulated water mass transformation on the Antarctic shelf to tides, topography and model resolution

Peer reviewe

Small-scale deformation of an Arctic sea ice floe detected by GPS and satellite imagery

Small-scale (~100 to 200 m) deformations of an Arctic sea ice floe were detected from multiple GPS-equipped buoys that were deployed on the same ice floe. Over a nine-month period three deformation events were recorded. At each case the event was of limited duration, each lasting less than a day. The events were highly compressive in nature with the area occupied by the buoy array decreasing by over half of the original area. The strain rate during the deformation, of the order of 10−5 s−1, is about three orders of magnitude larger than previous estimates for brittle fracturing for cracks of about 100 m in length. On the 2-day time scale, the strain rate became too small and none of the deformation events could be detected. This suggests that satellite data with longer time scales may significantly underestimate the amount of intermittent, small-scale brittle failure of total deformation. Taken as a whole, our results show the influence that large-scale wind stress can have on small-scale deformation. However, it is important to note that the impact of large-scale wind stress is also dependent on the properties of sea ice as well as on the spatial and temporal evolution of the underlying forces that influence the fracturing proces

Commentary on key aspects of fecal microbiota transplantation in small animal practice

The gastrointestinal tract of dogs, cats, and other mammals including humans harbors millions of beneficial microorganisms that regulate and maintain health. Fecal microbiota transplantation (FMT) is a procedure involving the administration of a fecal infusion from a healthy individual (donor) to a patient with disease to help improve health. Despite the effectiveness of FMT to treat intestinal disorders in humans, in particular recurrent Clostridium difficile infection, there is a paucity of scientific data regarding the application of FMT in veterinary patients. Here, we outline key aspects of FMT in small animal practice

The Grizzly, September 28, 1993

The Quilt\u27s Arrival: To Remember • Dawleys Appointed Biology Co-Chairs • Russian President Yeltsin Dissolves Parliament • Model UN Seeks New Delegation • Billy Joel Rocks Philly • Javapalooza • Big Al Day Exposed • Fitness Forum • Freshman Primer • Letter: Faculty Members Point Out Error • Tutorial Program Strengthens Ursinus • Ursinus Perceived as Anti-Gay • UC Training Staff Saves the Day • Bear Pack Way Ahead Again • Football Holds Off Western Maryland • Scooter\u27s Dayhttps://digitalcommons.ursinus.edu/grizzlynews/1319/thumbnail.jp

An environmentally benign antimicrobial nanoparticle based on a silver-infused lignin core

Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles

Structure of the human mTOR Complex I and its implications for rapamycin inhibition

The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth in response to the nutrient and energy status of the cell, and its deregulation is common in human cancers. Little is known about the overall architecture and subunit organization of this essential signaling complex. We have determined the three-dimensional (3D) structure of the fully assembled human mTORC1 by cryo-electron microscopy (cryo-EM). Our analyses reveal that mTORC1 is an obligate dimer with an overall rhomboid shape and a central cavity. The dimeric interfaces are formed by interlocking interactions between the mTOR and raptor subunits. Extended incubation with FKBP12-rapamycin compromises the structural integrity of mTORC1 in a stepwise manner, leading us to propose a model in which rapamycin inhibits mTORC1-mediated phosphorylation of 4E-BP1 and S6K1 through different mechanisms.National Institutes of Health (U.S.) (Grant AI47389)National Institutes of Health (U.S.) (Grant CA103866)United States. Dept. of Defense (W81XWH-07-1-0448)W. M. Keck Foundatio

Sensitivity of simulated water mass transformation on the Antarctic shelf to tides, topography and model resolution

Water mass transformation (WMT) around the Antarctic margin controls Antarctica Bottom Water formation and the abyssal limb of the global meridional overturning circulation, besides mediating ocean-ice shelf exchange, ice sheet stability and its contribution to sea level rise. However, the mechanisms controlling the rate of WMT in the Antarctic shelf are poorly understood due to the lack of observations and the inability of climate models to simulate those mechanisms, in particular beneath the floating ice shelves. We used a circum-Antarctic ocean-ice shelf model to assess the contribution of surface fluxes, mixing, and ocean-ice shelf interaction to the WMT on the continental shelf. The salt budget dominates the WMT rates, with only a secondary contribution from the heat budget. Basal melt of ice shelves drives buoyancy gain at lighter density classes (27.2<σθ< 27.6 kg m-3), while salt input associated with sea-ice growth in coastal polynyas drives buoyancy loss at heavier densities (σθ> 27.6). We found a large sensitivity of the WMT rates to model horizontal resolution, tides and topography within the Filchner-Ronne, East and West Antarctica ice shelf cavities. In the Filchner-Ronne Ice Shelf, an anticyclonic circulation in front of the Ronne Depression regulates the rates of basal melting/refreezing and WMT and is substantially affected by tides and model resolution. Model resolution is also found to affect the Antarctic Slope Current in both East and West Antarctica, impacting the on-shelf heat delivery, basal melt and WMT. Moreover, the representation of the ice shelf draft associated with model resolution impacts the freezing temperature and thus basal melt and WMT rates in the East Antarctica. These results highlight the importance of resolving small-scale features of the flow and topography, and to include the effects of tidal forcing, to adequately represent water mass transformations on the shelf that directly influence the abyssal global overturning circulation

The Grizzly, November 5, 1991

Red and Gold Day • Changes for Education Majors • Golf Cart Stolen • Unrest in the Quad • Alcohol Update • Fourth Annual Grizzly Network Career Day • U.S.G.A. Minutes • Chemical Awareness • Biology Department Update • Environmental Notes • Fraternities Experience Humanity of Habitat • The Winner Is: Mudslinger #1 • The Harm of Rumors • Priorities in College Athletics • Feed Your Mind • Halloween Flop • Soviet Art at Ursinus • The Quad Peacock • College Choir Performs Requiem • Senior Barn Bash • Goodfellas • Bears Rush by the Mules in 13-9 Upset • Volleyball Ends Season with a Loss • Field Hockey Passes by Princeton • Senior Runners Reflect on Seasonhttps://digitalcommons.ursinus.edu/grizzlynews/1282/thumbnail.jp