This study provides direct evidence that SARS human coronavirus is capable of infecting the central nervous system, and that Mig might be involved in the brain immunopathology of SARS.
Summary Mitochondrial diseases and aging are associated with defects in the oxidative phosphorylation machinery (OXPHOS), which are the only complexes composed of proteins encoded by separate genomes. To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcription factor that regulates mitochondria-to-nuclear communication during the mitochondrial UPR, via ChIP-sequencing. Surprisingly, in addition to regulating mitochondrial chaperone, OXPHOS complex assembly factor, and glycolysis genes, ATFS-1 bound directly to OXPHOS gene promoters in both the nuclear and mitochondrial genomes. Interestingly, atfs-1 was required to limit the accumulation of OXPHOS transcripts during mitochondrial stress, which required accumulation of ATFS-1 in the nucleus and mitochondria. Because balanced ATFS-1 accumulation promoted OXPHOS complex assembly and function, our data suggest that ATFS-1 stimulates respiratory recovery by fine-tuning OXPHOS expression to match the capacity of the suboptimal protein-folding environment in stressed mitochondria, while simultaneously increasing proteostasis capacity.
We report the first complete genome sequence of a marine invertebrate virus. White spot bacilliform virus (WSBV; or white spot syndrome virus) is a major shrimp pathogen with a high mortality rate and a wide host range. Its double-stranded circular DNA genome of 305,107 bp contains 181 open reading frames (ORFs). Nine homologous regions containing 47 repeated minifragments that include direct repeats, atypical inverted repeat sequences, and imperfect palindromes were identified. This is the largest animal virus that has been completely sequenced. Although WSBV is morphologically similar to insect baculovirus, the two viruses are not detectably related at the amino acid level. Rather, some WSBV genes are more homologous to eukaryotic genes than viral genes. In fact, sequence analysis indicates that WSBV differs from all known viruses, although a few genes display a weak homology to herpesvirus genes. Most of the ORFs encode proteins that bear no homology to any known proteins, either suggesting that WSBV represents a novel class of viruses or perhaps implying a significant evolutionary distance between marine and terrestrial viruses. The most unique feature of WSBV is the presence of an intact collagen gene, a gene encoding an extracellular matrix protein of animal cells that has never been found in any viruses. Determination of the genome of WSBV will facilitate a better understanding of the molecular mechanism underlying the pathogenesis of the WSBV virus and will also provide useful information concerning the evolution and divergence of marine and terrestrial animal viruses at the molecular level.White spot bacilliform virus (WSBV) or white spot syndrome virus (WSSV) is a major shrimp pathogen that is highly virulent in penaeid shrimp, the most important species used in aquaculture, and can also infect most species of crustacean (15, 32). Infection of penaeid shrimp by WSBV can result in mortality of up to 90 to 100% within 3 to 7 days (57). A major outbreak of WSBV infection in 1993 resulted in a 70% reduction in shrimp production in China (14, 57) and has raised major concerns in aquaculture around the world. Prevention and inhibition of infection by this virus can be difficult due largely to the ability of WSBV to survive for a long time in the environment (2 years in a shrimp pond) and also due to a poor understanding of this virus at the molecular level.WSBV was originally classified as an unassigned member of the Baculoviridae because of its rod-shaped, enveloped morphology (20). However, it was recently excluded from the baculovirus family and is temporarily unclassified due to the lack of molecular information (53). The virus is known generally as white spot syndrome virus (WSSV) (31), and a new genus name, Whispovirus, was proposed by Vlak et al. (48). Sequence analysis of individual genes and proteins later showed that most WSBV proteins bear poor sequence homology to baculovirus proteins but have repeated regions similar to those of some baculoviruses. To understand the molecular basis of viral repl...
Induction of IP-10 is a critical event in the initiation of immune-mediated acute lung injury and lymphocyte apoptosis during the development of SARS. Superinfection after the immune injury is the main cause of death. The prompt elevation of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 is a sign of superinfection, indicating a high risk of death.
Hyperphosphatemia is common in patients with chronic kidney disease and is increasingly associated with poor clinical outcomes. Current management of hyperphosphatemia with dietary restriction and oral phosphate binders often proves inadequate. Tenapanor, a minimally absorbed, small-molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), acts locally in the gastrointestinal tract to inhibit sodium absorption. Because tenapanor also reduces intestinal phosphate absorption, it may have potential as a therapy for hyperphosphatemia. We investigated the mechanism by which tenapanor reduces gastrointestinal phosphate uptake, using in vivo studies in rodents and translational experiments on human small intestinal stem cell-derived enteroid monolayers to model ion transport physiology. We found that tenapanor produces its effect by modulating tight junctions, which increases transepithelial electrical resistance (TEER) and reduces permeability to phosphate, reducing paracellular phosphate absorption. NHE3-deficient monolayers mimicked the phosphate phenotype of tenapanor treatment, and tenapanor did not affect TEER or phosphate flux in the absence of NHE3. Tenapanor also prevents active transcellular phosphate absorption compensation by decreasing the expression of NaPi2b, the major active intestinal phosphate transporter. In healthy human volunteers, tenapanor (15 mg, given twice daily for 4 days) increased stool phosphorus and decreased urinary phosphorus excretion. We determined that tenapanor reduces intestinal phosphate absorption predominantly through reduction of passive paracellular phosphate flux, an effect mediated exclusively via on-target NHE3 inhibition.
Visible light communication (VLC) using lightemitting-diodes (LEDs) has been a popular research area recently. VLC can provide a practical solution for indoor positioning. In this paper, the impact of multipath reflections on indoor VLC positioning is investigated, considering a complex indoor environment with walls, floor and ceiling. For the proposed positioning system, an LED bulb is the transmitter and a photodiode (PD) is the receiver to detect received signal strength (RSS) information. Combined deterministic and modified Monte Carlo (CDMMC) method is applied to compute the impulse response of the optical channel. Since power attenuation is applied to calculate the distance between the transmitter and receiver, the received power from each reflection order is analyzed. Finally, the positioning errors are estimated for all the locations over the room and compared with the previous works where no reflections considered. Three calibration approaches are proposed to decrease the effect of multipath reflections. Index Terms-Indoor positioning, visible light communication, multipath reflections, impulse response, received signal strength.
This paper proposes a novel indoor positioning algorithm using visible light communications (VLC). The algorithm is implemented by preinstalled light-emitting diode illumination systems. It recovers the VLC channel features from illuminating visible light and estimates receiver locations by analytically solving the Lambertian transmission equation group. According to our research, the algorithm is able to provide positioning resolution higher than 0.5 mm, in a practical indoor environment. The performance significantly exceeds conventional indoor positioning approaches using microwaves.
Type I interferons (IFNs) play central roles in innate immunity; however, overproduction of IFN can lead to immunopathology. Here, we demonstrate that adenosine deaminase acting on RNA 1 (ADAR1), an RNA-editing enzyme induced by interferon, is essential for cells to avoid inappropriate sensing of cytosolic RNA in an inducible knockout cell model – the primary mouse embryo fibroblast (MEF) derived from ADAR1 lox/lox & Cre-ER mice, as well as in HEK293 cells. ADAR1 suppresses viral and cellular RNA detection by RIG-I through its RNA binding rather than its RNA editing activity. DsRNA binds to both ADAR1 and RIG-I, but ADAR1 reduces RIG-I RNA binding. In the absence of ADAR1, cellular RNA stimulates type I IFN production without viral infection or exogenous RNA stimulation. Moreover, we showed in the ADAR1 inducible knockout mice that ADAR1 gene disruption results in a high level IFN production in neuronal tissues – the hallmark of Aicardi-Goutières Syndrome (AGS), a heritable autoimmune disease recently found to be associated with ADAR1 gene mutations. In summary, this study found that ADAR1 limits cytosolic RNA sensing by RIG-I through its RNA binding activity; therefore, ADAR1 suppresses type I IFN production stimulated by viral and cellular RNAs. These results explain why loss of ADARA1 causes IFN induction and also indicates a mechanism for the involvement of ADAR1 in autoimmune diseases such as AGS.
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