Axonal Control of the Adult Neural Stem Cell Niche

SUMMARYThe ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C

Addressing the climate challenge

In 2021, colleagues from across the University of Birmingham community were invited to write articles about topics relevant to the COP26 climate change summit. In this series of articles, experts from across many different disciplines provide new insight and evidence on how we might all understand and tackle climate change

Enhanced Precision Through Multiple Reads for LDPC Decoding in Flash Memories

Abstract—Multiple reads of the same Flash memory cell with distinct word-line voltages provide enhanced precision for LDPC decoding. In this paper, the word-line voltages are optimized by maximizing the mutual information (MI) of the quantized channel. The enhanced precision from a few additional reads allows FER performance to approach that of full precision soft information and enables an LDPC code to significantly outperform a BCH code. A constant-ratio constraint provides a significant simplification in the optimization with no noticeable loss in performance. For a well-designed LDPC code, the quantization that maximizes the mutual information also minimizes the frame error rate in our simulations. However, for an example LDPC code with a high error floor caused by small absorbing sets, the MMI quantization does not provide the lowest frame error rate. The best quantization in this case introduces more erasures than would be optimal for the channel MI in order to mitigate the absorbing sets of the poorly designed code. The paper also identifies a trade-off in LDPC code design when decoding is performed with multiple precision levels; the best code at one level of precision will typically not be the best code at a different level of precision

Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells

Hepatitis C virus non-structural protein NS5A plays an important role in viral replication and various cellular events. To gain further insight into the function of NS5A, we screened a human fetal liver cDNA library for its interacting proteins using the yeast two-hybrid system. FKBP38, a 38 kDa immunosuppressant FK506-binding protein, was identified and its interaction with NS5A was confirmed by both in vitro and in vivo. The interaction was mapped to the amino acids 148-236 of NS5A containing a BH domain (Bcl-2 homology domain). Besides, both NS5A and FKBP38 were found to localize in mitochondria and endoplasmic reticulum. Moreover, NS5A stably expressing Huh7 hepatoma cells showed more resistance to apoptosis and such inhibition of apoptosis could specifically be abrogated by depletion of FKBP38 using RNA interference. These results indicate that HCV NS5A inhibits apoptosis through interaction with FKBP38.</p

A new chitosan-based thermosensitive nanoplatform for combined photothermal and chemotherapy

Targeting the delivery of anti-cancer drugs to a tumor site is essential for effective treatment and to ensure minimal damage to healthy cells and tissues. In this work, a chitosan-based nanoplatform was constructed for combined photothermal therapy and chemotherapy of breast cancer. The pH-sensitive and biocompatible biopolymer chitosan (CS) was grafted with N-vinylcaprolactam (NVCL) and modified with biotin (Bio), imparting it with temperature sensitive property and the ability of active targeting. The polymer self-assembled to give nanoparticles (NPs) loaded with indocyanine green (ICG) and doxorubicin (DOX). When the NPs are exposed to near-infrared (NIR) laser irradiation, ICG converts the light to heat, inducing a significant phase transition in NPs and facilitating the release of the drug cargo. In addition, the solubility of chitosan is increased in the slightly acidic microenvironment of the tumor site, which also promotes drug release. A detailed analysis of the NPs both in vitro and in vivo showed that the carrier system is biocompatible, while the drug-loaded NPs are selectively taken up by cancer cells. Particularly when augmented with NIR irradiation, this leads to potent cell death in vitro and also in an in vivo murine xenograft model of breast cancer

Axonal control of the adult neural stem cell niche

The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSCs) in the walls of the lateral ventricles of the adult brain. How the adult brain\u27s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C