Genome-wide Integrative Analysis of Zika-Virus-Infected Neuronal Stem Cells Reveals Roles for MicroRNAs in Cell Cycle and Stemness.

Zika virus (ZIKV) infection is implicated in severe fetal developmental disorders, including microcephaly. MicroRNAs (miRNAs) post-transcriptionally regulate numerous processes associated with viral infection and neurodegeneration, but their contribution to ZIKV pathogenesis is unclear. We analyzed the mRNA and miRNA transcriptomes of human neuronal stem cells (hNSCs) during infection with ZIKV MR766 and Paraiba strains. Integration of the miRNA and mRNA expression data into regulatory interaction networks showed that ZIKV infection resulted in miRNA-mediated repression of genes regulating the cell cycle, stem cell maintenance, and neurogenesis. Bioinformatics analysis of Argonaute-bound RNAs in ZIKV-infected hNSCs identified a number of miRNAs with predicted involvement in microcephaly, including miR-124-3p, which dysregulates NSC maintenance through repression of the transferrin receptor (TFRC). Consistent with this, ZIKV infection upregulated miR-124-3p and downregulated TFRC mRNA in ZIKV-infected hNSCs and mouse brain tissue. These data provide insights into the roles of miRNAs in ZIKV pathogenesis, particularly the microcephaly phenotype

Zika virus infection reprograms global transcription of host cells to allow sustained infection.

Zika virus (ZIKV) is an emerging virus causally linked to neurological disorders, including congenital microcephaly and Guillain-Barré syndrome. There are currently no targeted therapies for ZIKV infection. To identify novel antiviral targets and to elucidate the mechanisms by which ZIKV exploits the host cell machinery to support sustained replication, we analyzed the transcriptomic landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived macrophage cell lines before and after ZIKV infection. The four cell types differed in their susceptibility to ZIKV infection, consistent with differences in their expression of viral response genes before infection. Clustering and network analyses of genes differentially expressed after ZIKV infection revealed changes related to the adaptive immune system, angiogenesis and host metabolic processes that are conducive to sustained viral production. Genes related to the adaptive immune response were downregulated in microglia cells, suggesting that ZIKV effectively evades the immune response after reaching the central nervous system. Like other viruses, ZIKV diverts host cell resources and reprograms the metabolic machinery to support RNA metabolism, ATP production and glycolysis. Consistent with these transcriptomic analyses, nucleoside metabolic inhibitors abrogated ZIKV replication in microglia cells

Investigation of Pyrolyzing Ablators Using a Gas Injection Probe

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143112/1/6.2017-0437.pd

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Outdoor shade detection using smartphone sensors

This thesis presents a full end-to-end system for collecting information about light and shade across a large campus. The system includes several components, including the smartphone app, the cloud database, and the web application. The system includes multiple applications designed to utilize and test the capabilities of Android smartphone sensors, specifically the light sensors and positional orientation sensors. The first of these applications is a simple Android application which uses sensors to collect data on the CSUN campus (light and orientation) along with other environmental data provided from external sources (current geographic location, provided by Google Maps Services). The data is sent to a cloud database, where it is queried for use in a web application. The web application fetches the data to display it on map markers, fuses the data together based on location while getting rid of any erroneous data obtained during data collection, and implements a 'shade casting entity detection' component that indicates where shade casting entities are based on the illuminance values, orientation values (x, y, z), and the time of day. The results of this thesis test the accuracy of smartphone sensors based on the locational comparison between the shade casting entities located by the system and the actual shade casting entities shown on the satellite map view in reality

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing

Loss of CD103+ DCs and Mucosal IL-17+ and IL-22+ Lymphocytes is Associated with Mucosal Damage in SIV Infection

HIV/SIV disease progression is associated with multifocal damage to the GI tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of IL-17-producing lymphocytes, cells that microarray analysis showed express genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ DCs after SIV infection which associated with loss of IL-17 and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and co-culture of CD103+ DCs and naïve T-cells led to increased IL17A and RORc expression in differentiating T-cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis

Capacity Management in Agricultural Commodity Processing and Application in the Palm Industry

This paper examines the capacity investment decisions of a processor that uses a commodity input to produce both a commodity output and a by-product in the context of agricultural industries. We employ a multiperiod model to study the optimal one-time processing and (output) storage capacity investment decisions—in addition to the periodic processing and inventory decisions—when both input and output spot prices as well as production yield are uncertain. We characterize the optimal decisions and perform sensitivity analysis to investigate how spot price uncertainty affects the processor’s optimal capacity and profitability. Using a calibration based on the palm industry, we study (both numerically and analytically) the performance of a variety of heuristic capacity investment policies that can be used in practice. We find that if the yield uncertainty is ignored in capacity planning, then basing those plans on the average yield is preferable to basing them (as often occurs in practice) on the maximum yield. However, planning based on the average yield performs well only when the relative (processing-to-storage) capacity investment cost is high; otherwise, it leads to a significant loss of profit. We also find that ignoring spot price uncertainty in capacity planning results in a relatively small profit loss. In contrast, ignoring by-product revenue—which constitutes a small portion of total revenues—during capacity planning substantially reduces the processor’s profit. The online appendix is available at https://doi.org/10.1287/msom.2017.0624 . </jats:p

Platelets and mast cells promote pathogenic eosinophil recruitment during invasive fungal infection via the 5-HIAA-GPR35 ligand-receptor system

Cryptococcus neoformans is the leading cause of fungal meningitis and is characterized by pathogenic eosinophil accumulation in the context of type-2 inflammation. The chemoattractant receptor GPR35 is expressed by granulocytes and promotes their migration to the inflammatory mediator 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. Given the inflammatory nature of cryptococcal infection, we examined the role of GPR35 in the circuitry underlying cell recruitment to the lung. GPR35 deficiency dampened eosinophil recruitment and fungal growth, whereas overexpression promoted eosinophil homing to airways and fungal replication. Activated platelets and mast cells were the sources of GPR35 ligand activity and pharmacological inhibition of serotonin conversion to 5-HIAA, or genetic deficiency in 5-HIAA production by platelets and mast cells resulted in more efficient clearance of Cryptococcus. Thus, the 5-HIAA-GPR35 axis is an eosinophil chemoattractant receptor system that modulates the clearance of a lethal fungal pathogen, with implications for the use of serotonin metabolism inhibitors in the treatment of fungal infections