Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin

Background

Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated.

Results

To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ) and the subgranular zone (SGZ). We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (Survivin ^Camcre ) with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. Survivin ^Camcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning.

Conclusions

The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.     

Functional effects of spinocerebellar ataxia type 13 mutations are conserved in zebrafish Kv3.3 channels

Background  

The zebrafish has been suggested as a model system for studying human diseases that affect nervous system function and motor output. However, few of the ion channels that control neuronal activity in zebrafish have been characterized. Here, we have identified zebrafish orthologs of voltage-dependent Kv3 (KCNC) K⁺ channels. Kv3 channels have specialized gating properties that facilitate high-frequency, repetitive firing in fast-spiking neurons. Mutations in human Kv3.3 cause spinocerebellar ataxia type 13 (SCA13), an autosomal dominant genetic disease that exists in distinct neurodevelopmental and neurodegenerative forms. To assess the potential usefulness of the zebrafish as a model system for SCA13, we have characterized the functional properties of zebrafish Kv3.3 channels with and without mutations analogous to those that cause SCA13.     

Determining uterine blood flow in pregnancy with magnetic resonance imaging

Objective

The purpose of this study is to determine the feasibility of measuring total uterine blood flow in pregnancy using magnetic resonance imaging (MRI) technique.

Methods

Uterine blood flow was determined in pregnant women in whom MRI was being carried out to assess a fetal anomaly. A two-dimensional time-of-flight magnetic resonance (MR) angiogram sequence was performed. Scout images and a peripherally gated phase contrast MR sequence were planned to study simultaneous blood flow in the uterine and ovarian arteries.

Results

The MR pelvic angiogram sequence was completed in 13 women. The uterine arteries were visualized and their cross-sectional area determined. The complexity of the pelvic blood supply prevented the calculation of blood flow velocity and, thus, total uterine blood flow.

Conclusion

The measurement of total uterine blood flow during pregnancy was not possible using our MR technique. The ovarian vessels were not consistently visualized. Doppler ultrasonography remains the best modality by which to estimate total uterine blood flow in pregnancy.     

Neutron enhancement from laser interaction with a critical fluid

We discuss experimentally and theoretically neutron production from the laser driven explosion of gas clusters prepared near the liquid-gas critical point. We let deuterated methane that was prepared very close to its critical temperature and pressure expand through a conical nozzle to create clusters, and then irradiated those clusters with a high intensity pulse from the Texas Petawatt Laser. After ionization, the clusters explode producing energetic ions, some of which fuse with resultant neutron emission. We show that the critical fluctuations present in the nozzle before the expansion influence the dynamics of neutron production. Neutron production near the critical point follows a power law, which is a signature of a second order phase transition and it is consistent with the Fisher model. This result might be relevant for energy production from fusion reactions.     

Inverse potential scaling in co-electrocatalytic activity for CO2 reduction through redox mediator tuning and catalyst design

Electrocatalytic CO₂ reduction is an attractive strategy to mitigate the continuous rise in atmospheric CO₂ concentrations and generate value-added chemical products. A possible strategy to increase the activity of molecular systems for these reactions is the co-catalytic use of redox mediators (RMs), which direct reducing equivalents from the electrode surface to the active site. Recently, we demonstrated that a sulfone-based RM could trigger co-electrocatalytic CO₂ reduction via an inner-sphere mechanism under aprotic conditions. Here, we provide support for inner-sphere cooperativity under protic conditions by synthetically modulating the mediator to increase activity at lower overpotentials (inverse potential scaling). Furthermore, we show that both the intrinsic and co-catalytic performance of the Cr-centered catalyst can be enhanced by ligand design. By tuning both the Cr-centered catalyst and RM appropriately, an optimized co-electrocatalytic system with quantitative selectivity for CO at an overpotential (η) of 280 mV and turnover frequency (TOF) of 194 s⁻¹ is obtained, representing a three-fold increase in co-catalytic activity at 130 mV lower overpotential than our original report. Importantly, this work lays the foundation of a powerful tool for developing co-catalytic systems for homogeneous electrochemical reactions.

The use of sulfone-based redox mediators in electrocatalytic CO₂ reduction by Cr-centered complexes enhances the turnover frequencies at lower overpotentials via inner-sphere electron transfer and pancake bonding.     

Aquaculture Production of the Brown Seaweeds Laminaria digitata and Macrocystis pyrifera: Applications in Food and Pharmaceuticals

Seaweeds have a long history of use as food, as flavouring agents, and find use in traditional folk medicine. Seaweed products range from food, feed, and dietary supplements to pharmaceuticals, and from bioenergy intermediates to materials. At present, 98% of the seaweed required by the seaweed industry is provided by five genera and only ten species. The two brown kelp seaweeds Laminaria digitata, a native Irish species, and Macrocystis pyrifera, a native New Zealand species, are not included in these eleven species, although they have been used as dietary supplements and as animal and fish feed. The properties associated with the polysaccharides and proteins from these two species have resulted in increased interest in them, enabling their use as functional foods. Improvements and optimisations in aquaculture methods and bioproduct extractions are essential to realise the commercial potential of these seaweeds. Recent advances in optimising these processes are outlined in this review, as well as potential future applications of L. digitata and, to a greater extent, M. pyrifera which, to date, has been predominately only wild-harvested. These include bio-refinery processing to produce ingredients for nutricosmetics, functional foods, cosmeceuticals, and bioplastics. Areas that currently limit the commercial potential of these two species are highlighted.     

Reconfiguration of connected graph partitions

Motivated by recent computational models for redistricting and detection of gerrymandering, we study the following problem on graph partitions. Given a graph $G$ and an integer $k\ge 1$, a $k$-district map of $G$ is a partition of $V\left(G\right)$ into $k$ nonempty subsets, called districts, each of which induces a connected subgraph of $G$. A switch is an operation that modifies a $k$-district map by reassigning a subset of vertices from one district to an adjacent district; a 1-switch is a switch that moves a single vertex. We study the connectivity of the configuration space of all $k$-district maps of a graph $G$ under 1-switch operations. We give a combinatorial characterization for the connectedness of this space that can be tested efficiently. We prove that it is PSPACE-complete to decide whether there exists a sequence of 1-switches that takes a given $k$-district map into another; and NP-hard to find the shortest such sequence (even if a sequence of polynomial lengths is known to exist). We also present efficient algorithms for computing a sequence of 1-switches that take a given $k$-district map into another when the space is connected, and show that these algorithms perform a worst-case optimal number of switches up to constant factors.     

Approaching Dianionic Tetraoxadiborecine Macrocycles: 10-Membered Bora-Crown Ethers Incorporating Borafluorenate Units

The addition of non-benzenoid quinones, acenapthenequinone or aceanthrenequinone, to the 9-carbene-9-borafluorene monoanion ( 1 ) affords the first examples of dianionic 10-membered bora-crown ethers ( 2 – 5 ), which are characterized by multi-nuclear NMR spectroscopy (¹H, ¹³C, ¹¹B), X-ray crystallography, elemental analysis, and UV/Vis spectroscopy. These tetraoxadiborecines have distinct absorption profiles based on the positioning of the alkali metal cations. When compound 4 , which has a vacant C₄B₂O₄ cavity, is reacted with sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, a color change from purple to orange serves as a visual indicator of metal binding to the central ring, whereby the Na⁺ ion coordinates to four oxygen atoms. A detailed theoretical analysis of the calculated reaction energetics is provided to gain insight into the reaction mechanism for the formation of 2 – 5 . These data, and the electronic structures of proposed intermediates, indicate that the reaction proceeds via a boron enolate intermediate.