A genome-wide RNAi screen reveals multiple regulators of caspase activation

Apoptosis is an evolutionally conserved cellular suicide mechanism that can be activated in response to a variety of stressful stimuli. Increasing evidence suggests that apoptotic regulation relies on specialized cell death signaling pathways and also integrates diverse signals from additional regulatory circuits, including those of cellular homeostasis. We present a genome-wide RNA interference screen to systematically identify regulators of apoptosis induced by DNA damage in Drosophila melanogaster cells. We identify 47 double- stranded RNA that target a functionally diverse set of genes, including several with a known function in promoting cell death. Further characterization uncovers 10 genes that influence caspase activation upon the removal of Drosophila inhibitor of apoptosis 1. This set includes the Drosophila initiator caspase Dronc and, surprisingly, several metabolic regulators, a candidate tumor suppressor, Charlatan, and an N-acetyltransferase, ARD1. Importantly, several of these genes show functional conservation in regulating apoptosis in mammalian cells. Our data suggest a previously unappreciated fundamental connection between various cellular processes and caspase-dependent cell death

Relationship of Agronomic Practices to Soil Nitrogen Dynamics

Soil nitrogen (N) dynamics are a major concern of soil nutrient status and its supply for crop uptake and growth. They are a central focus of agroecosystems. Agronomic practices play a central role in regulating soil N dynamics; the methodologies for investigating soil N mineralization are diverse, but debatable. This chapter discusses the pros and cons of different methods for measuring soil N mineralization, including laboratory, in-situ, and modeling procedures. This chapter illustrates the influence of agronomic practices on root architecture that potentially affects crop nutrient uptake. The relationship between agronomic practices and soil N dynamics were fully discussed, which can substantially inform soil fertility and crop nutrition management

A directionally tunable but frequency-invariant beamformer on an acoustic velocity-sensor triad to enhance speech perception

Herein investigated are computationally simple microphone-array beamformers that are independent of the frequency-spectra of all signals, all interference, and all noises. These beamformers allow the listener to tune the desired azimuth-elevation “look direction.” No prior information is needed of the interference. These beamformers deploy a physically compact triad of three collocated but orthogonally oriented velocity sensors. These proposed schemes’ efficacy is verified by a jury test, using simulated data constructed with Mandarin Chinese (a.k.a. Putonghua) speech samples. For example, a desired speech signal, originally at a very adverse signal-to-interference-and-noise power ratio (SINR) of -30 dB, may be processed to become fully intelligible to the jury

Chalcogenide Glass-on-Graphene Photonics

Two-dimensional (2-D) materials are of tremendous interest to integrated photonics given their singular optical characteristics spanning light emission, modulation, saturable absorption, and nonlinear optics. To harness their optical properties, these atomically thin materials are usually attached onto prefabricated devices via a transfer process. In this paper, we present a new route for 2-D material integration with planar photonics. Central to this approach is the use of chalcogenide glass, a multifunctional material which can be directly deposited and patterned on a wide variety of 2-D materials and can simultaneously function as the light guiding medium, a gate dielectric, and a passivation layer for 2-D materials. Besides claiming improved fabrication yield and throughput compared to the traditional transfer process, our technique also enables unconventional multilayer device geometries optimally designed for enhancing light-matter interactions in the 2-D layers. Capitalizing on this facile integration method, we demonstrate a series of high-performance glass-on-graphene devices including ultra-broadband on-chip polarizers, energy-efficient thermo-optic switches, as well as graphene-based mid-infrared (mid-IR) waveguide-integrated photodetectors and modulators

Bmi-1 Absence Causes Premature Brain Degeneration

Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle regulation and cell senescence. Its absence results in generalized astrogliosis and epilepsy during the postnatal development, but the underlying mechanisms are poorly understood. Here, we demonstrate the occurrence of oxidative stress in the brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis and brain mitochondrial damage. Moreover, astroglial glutamate transporters and glutamine synthetase decreased in the Bmi-1 null hippocampus, which might contribute to the sporadic epileptic-like seizures in these mice. These results indicate that Bmi-1 is required for maintaining endogenous antioxidant defenses in the brain, and its absence subsequently causes premature brain degeneration

Toll-Like Receptor 9 Is Required for Opioid-Induced Microglia Apoptosis

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6), the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or µ-opioid receptor (µOR) deficient primary microglia, suggesting an involvement of MAPK and µOR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require μOR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and µOR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of µOR is capable of preventing opioid-induced brain damage

RNF185, a Novel Mitochondrial Ubiquitin E3 Ligase, Regulates Autophagy through Interaction with BNIP1

Autophagy is an evolutionarily conserved catabolic process that allows recycling of cytoplasmic organelles, such as mitochondria, to offer a bioenergetically efficient pathway for cell survival. Considerable progress has been made in characterizing mitochondrial autophagy. However, the dedicated ubiquitin E3 ligases targeting mitochondria for autophagy have not been revealed. Here we show that human RNF185 is a mitochondrial ubiquitin E3 ligase that regulates selective mitochondrial autophagy in cultured cells. The two C-terminal transmembrane domains of human RNF185 mediate its localization to mitochondrial outer membrane. RNF185 stimulates LC3II accumulation and the formation of autophagolysosomes in human cell lines. We further identified the Bcl-2 family protein BNIP1 as one of the substrates for RNF185. Human BNIP1 colocalizes with RNF185 at mitochondria and is polyubiquitinated by RNF185 through K63-based ubiquitin linkage in vivo. The polyubiquitinated BNIP1 is capable of recruiting autophagy receptor p62, which simultaneously binds both ubiquitin and LC3 to link ubiquitination and autophagy. Our study might reveal a novel RNF185-mediated mechanism for modulating mitochondrial homeostasis through autophagy