The role of microglia cells in Alzheimer’s disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4+) and non-containing (XO4−) microglia from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories in ageing and AD mice. XO4+ microglial transcriptomes demonstrated dysregulated expression of genes associated with late onset AD. We further showed that the transcriptional program associated with XO4+ microglia from mice is present in a subset of human microglia isolated from brains of individuals with AD. XO4− microglia displayed transcriptional signatures associated with accelerated ageing and contained more intracellular post-synaptic material than XO4+ microglia, despite reduced active synaptosome phagocytosis. We identified HIF1α as potentially regulating synaptosome phagocytosis in vitro using primary human microglia, and BV2 mouse microglial cells. Together, these findings provide insight into molecular mechanisms underpinning the functional diversity of microglia in AD.
Mitochondria form networks. Formation of mitochondrial networks is important for maintaining mitochondrial DNA integrity and interchanging mitochondrial material, whereas disruption of the mitochondrial network affects mitochondrial functions. According to the current view, mitochondrial networks are formed by fusion of individual mitochondria. Here, we report a new mechanism for formation of mitochondrial networks through KIF5B-mediated dynamic tubulation of mitochondria. We found that KIF5B pulls thin, highly dynamic tubules out of mitochondria. Fusion of these dynamic tubules, which is mediated by mitofusins, gives rise to the mitochondrial network. We further demonstrated that dynamic tubulation and fusion is sufficient for mitochondrial network formation, by reconstituting mitochondrial networks in vitro using purified fusion-competent mitochondria, recombinant KIF5B, and polymerized microtubules. Interestingly, KIF5B only controls network formation in the peripheral zone of the cell, indicating that the mitochondrial network is divided into subzones, which may be constructed by different mechanisms. Our data not only uncover an essential mechanism for mitochondrial network formation, but also reveal that different parts of the mitochondrial network are formed by different mechanisms.
Face parsing is a basic task in face image analysis. It amounts to labeling each pixel with appropriate facial parts such as eyes and nose. In the paper, we present a interlinked convolutional neural network (iCNN) for solving this problem in an end-to-end fashion. It consists of multiple convolutional neural networks (CNNs) taking input in different scales. A special interlinking layer is designed to allow the CNNs to exchange information, enabling them to integrate local and contextual information efficiently. The hallmark of iCNN is the extensive use of downsampling and upsampling in the interlinking layers, while traditional CNNs usually uses downsampling only. A two-stage pipeline is proposed for face parsing and both stages use iCNN. The first stage localizes facial parts in the size-reduced image and the second stage labels the pixels in the identified facial parts in the original image. On a benchmark dataset we have obtained better results than the state-of-the-art methods.
Organic-inorganic hybrid perovskites (OIHPs) have been a hot research topic for their advanced structural and functional features, which cover almost all the research fields of intelligent materials including ferroelectric, photovoltaic, fluorescent, dielectric, etc. However, the OIHPs ferroelastic semiconductor with optical-electrical response has been a huge challenge and rarely reported. In this work, a rare and interesting hybrid perovskite ferroelastic semiconductor [BFDA]PbBr 3 was synthesized, which benefits from the structural advantage of a long tail BFDA to be balanced by the suitable inorganic framework (BFDA=benzyl-(2-fluoro-ethyl)-dimethyl-ammonium). The [BFDA]PbBr 3 shows the high temperature ferroelastic phase transition at 365 K and a direct band gap of 3.33 eV. In addition, it can emit the charming orange pink light under 365 nm UV lamp. To combine with the ferroelastic, optical and dielectric properties, [BFDA]PbBr 3 can be identified as a very rare
MYH14 is a member of the myosin family, which has been implicated in many motile processes such as ion-channel gating, organelle translocation, and the cytoskeleton rearrangement. Mutations in MYH14 lead to a DFNA4-type hearing impairment. Further evidence also shows that MYH14 is a candidate noise-induced hearing loss (NIHL) susceptible gene. However, the specific roles of MYH14 in auditory function and NIHL are not fully understood. In the present study, we used CRISPR/Cas9 technology to establish a Myh14 knockout mice line in CBA/CaJ background (now referred to as Myh14−/− mice) and clarify the role of MYH14 in the cochlea and NIHL. We found that Myh14−/− mice did not exhibit significant hearing loss until five months of age. In addition, Myh14−/− mice were more vulnerable to high intensity noise compared to control mice. More significant outer hair cell loss was observed in Myh14−/− mice than in wild type controls after acoustic trauma. Our findings suggest that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.