Heterogeneity in Kv2 Channel Expression Shapes Action Potential Characteristics and Firing Patterns in CA1 versus CA2 Hippocampal Pyramidal Neurons.

The CA1 region of the hippocampus plays a critical role in spatial and contextual memory, and has well-established circuitry, function and plasticity. In contrast, the properties of the flanking CA2 pyramidal neurons (PNs), important for social memory, and lacking CA1-like plasticity, remain relatively understudied. In particular, little is known regarding the expression of voltage-gated K+ (Kv) channels and the contribution of these channels to the distinct properties of intrinsic excitability, action potential (AP) waveform, firing patterns and neurotransmission between CA1 and CA2 PNs. In the present study, we used multiplex fluorescence immunolabeling of mouse brain sections, and whole-cell recordings in acute mouse brain slices, to define the role of heterogeneous expression of Kv2 family Kv channels in CA1 versus CA2 pyramidal cell excitability. Our results show that the somatodendritic delayed rectifier Kv channel subunits Kv2.1, Kv2.2, and their auxiliary subunit AMIGO-1 have region-specific differences in expression in PNs, with the highest expression levels in CA1, a sharp decrease at the CA1-CA2 boundary, and significantly reduced levels in CA2 neurons. PNs in CA1 exhibit a robust contribution of Guangxitoxin-1E-sensitive Kv2-based delayed rectifier current to AP shape and after-hyperpolarization potential (AHP) relative to that seen in CA2 PNs. Our results indicate that robust Kv2 channel expression confers a distinct pattern of intrinsic excitability to CA1 PNs, potentially contributing to their different roles in hippocampal network function

Enantio- and Diastereoselective 1,2-Additions to α-Ketoesters with Diborylmethane and Substituted 1,1-Diborylalkanes

The catalytic enantioselective synthesis of boronate-substituted tertiary alcohols through additions of diborylmethane and substituted 1,1-diborylalkanes to α-ketoesters is reported. The reactions are catalyzed by readily available chiral phosphine/copper(I) complexes and produce β-hydroxyboronates containing up to two contiguous stereogenic centers in up to 99:1 e.r. and greater than 20:1 d.r. The utility of the organoboron products is demonstrated through several chemoselective functionalizations. Evidence indicates the reactions occur via an enantioenriched α-boryl-copper-alkyl intermediate

Perceptual and Semantic Contributions to Repetition Priming of Environmental Sounds

Repetition of environmental sounds, like their visual counterparts, can facilitate behavior and modulate neural responses, exemplifying plasticity in how auditory objects are represented or accessed. It remains controversial whether such repetition priming/suppression involves solely plasticity based on acoustic features and/or also access to semantic features. To evaluate contributions of physical and semantic features in eliciting repetition-induced plasticity, the present functional magnetic resonance imaging (fMRI) study repeated either identical or different exemplars of the initially presented object; reasoning that identical exemplars share both physical and semantic features, whereas different exemplars share only semantic features. Participants performed a living/man-made categorization task while being scanned at 3T. Repeated stimuli of both types significantly facilitated reaction times versus initial presentations, demonstrating perceptual and semantic repetition priming. There was also repetition suppression of fMRI activity within overlapping temporal, premotor, and prefrontal regions of the auditory "what” pathway. Importantly, the magnitude of suppression effects was equivalent for both physically identical and semantically related exemplars. That the degree of repetition suppression was irrespective of whether or not both perceptual and semantic information was repeated is suggestive of a degree of acoustically independent semantic analysis in how object representations are maintained and retrieve

The effect of schizotypy on spatial learning in an environment with a distinctive shape

In two experiments, participants completed the Oxford-Liverpool Inventory of Feelings and Experiences measuring schizotypal traits across four dimensions (unusual experiences, cognitive disorganization, introvertive anhedonia, and impulsive non-conformity). They then took part in a virtual navigation task where they were required to learn about the position of a hidden goal with reference to geometric cues of a rectangular arena or rely on colored wall panels to find the hidden goal in a square-shaped arena. Unusual experience and cognitive disorganization were significant predictors of the use of geometric cues, but no significant predictors were found for the use of wall panels. Implications to hippocampal function and the clinical domain are considered

Towing tank and flume testing of passively adaptive composite tidal turbine blades

Composite tidal turbine blades with bend-twist (BT) coupled layups allow the blade to self-adapt to local site conditions by passively twisting. Passive feathering has the potential to increase annual energy production and shed thrust loads and power under extreme tidal flows. Decreased hydrodynamic thrust and power during extreme conditions means that the turbine support structure, generator, and other components can be sized more appropriately, resulting in a higher utilization factor and increased cost effectiveness

Cognitive Information Processing

Contains research objectives and summary of research.Madeline Moses FundNational Science Foundation (Grant GK-33736X1)National Institutes of Health (Grant 5 PO1 GM19428-02)Peter Bent Brigham Hospital, Purchase Order G-33196Associated Press (Grant)National Institutes of Health (Grant 5 PO1 GM14940-07

BMP-7 Does Not Protect against Bleomycin-Induced Lung or Skin Fibrosis

Bone morphogenic protein (BMP)-7 is a member of the BMP family which are structurally and functionally related, and part of the TGFβ super family of growth factors. BMP-7 has been reported to inhibit renal fibrosis and TGFβ1-induced epithelial-mesenchymal transition (EMT), in part through negative interactions with TGFβ1 induced Smad 2/3 activation. We utilized in vivo bleomycin-induced fibrosis models in the skin and lung to determine the potential therapeutic effect of BMP-7. We then determined the effect of BMP-7 on TGFβ1-induced EMT in lung epithelial cells and collagen production by human lung fibroblasts. We show that BMP-7 did not affect bleomycin-induced fibrosis in either the lung or skin in vivo; had no effect on expression of pro-fibrotic genes by human lung fibroblasts, either at rest or following exposure to TGFβ1; and did not modulate TGFβ1 -induced EMT in human lung epithelial cells. Taken together our data indicates that BMP-7 has no anti-fibrotic effect in lung or skin fibrosis either in vivo or in vitro. This suggests that the therapeutic options for BMP-7 may be confined to the renal compartment

Multisensory Interactions within Human Primary Cortices Revealed by BOLD Dynamics

Whether signals from different sensory modalities converge and interact within primary cortices in humans is unresolved, despite emerging evidence in animals. This is partially because of debates concerning the appropriate analyses of functional magnetic resonance imaging (fMRI) data in response to multisensory phenomena. Using event-related fMRI, we observed that simple auditory stimuli (noise bursts) activated primary visual cortices and that simple visual stimuli (checkerboards) activated primary auditory cortices, indicative of multisensory convergence. Moreover, analyses of blood oxygen level-dependent response dynamics revealed facilitation of hemodynamic response peak latencies and slopes for multisensory auditory-visual stimuli versus either unisensory condition, indicative of multisensory interactions within primary sensory cortices. Neural processing at the lowest cortical levels can be modulated by interactions between the senses. Temporal information in fMRI data can reveal these modulations and overcome analytic and interpretational challenges of more traditional procedures. In addition to providing an essential translational link with animal models, these results suggest that longstanding notions of cortical organization need to be revised to include multisensory interactions as an inherent component of functional brain organizatio

Chandra X-Ray Observations of Two Unusual BAL Quasars

We report sensitive Chandra X-ray non-detections of two unusual, luminous Iron Low-Ionization Broad Absorption Line Quasars (FeLoBALs). The observations do detect a non-BAL, wide-binary companion quasar to one of the FeLoBAL quasars. We combine X-ray-derived column density lower limits (assuming solar metallicity) with column densities measured from ultraviolet spectra and CLOUDY photoionization simulations to explore whether constant density slabs at broad line region densities can match the physical parameters of these two BAL outflows, and find that they cannot. In the "overlapping-trough" object SDSS J0300+0048, we measure the column density of the X-ray absorbing gas to be N_H >= 1.8 x 1024 cm-2. From the presence of Fe II UV78 absorption but lack of Fe II UV195/UV196 absorption, we infer the density in that part of the absorbing region to be n_e ~ 106 cm-3. We do find that a slab of gas at that density might be able to explain this object's absorption. In the Fe III-dominant object SDSS J2215-0045, the X-ray absorbing column density of N_H >= 3.4 x 1024 cm-2 is consistent with the Fe III-derived N_H >= 2 x 1022 cm-2 provided the ionization parameter is log U > 1.0 for both the n_e = 1011 cm-3 and n_e = 1012 cm-3 scenarios considered (such densities are required to produce Fe III absorption without Fe II absorption). However, the velocity width of the absorption rules out its being concentrated in a single slab at these densities. Instead, this object's spectrum can be explained by a low density, high ionization and high temperature disk wind that encounters and ablates higher density, lower ionization Fe III-emitting clumps.Comment: 18 pages, 6 figure