Project description:Cognitively normal brains are compared to sporadic AD and Down syndrome brains with AD for comparison of two different forms of Alzheimer's disease
Project description:Small molecule inhibitors of mitochondrial electron transport chain (ETC) hold significant promise in the field of mitochondrial research and aging biology. In this study, we studied two molecules: mycothiazole (MTZ) - isolated from the marine sponge P. mycofijiensis and its semisynthetic acetylated derivative 8-O-acetylmycothiazole (8-OAc) as efficient alternatives for their high efficiency to inhibit ETC complex I function. Similar to rotenone, a widely used complex I inhibitor, these two compounds showed anticancer activity and strikingly demonstrate a lack of toxicity to non-cancer cells, a highly beneficial feature in the development of anti-cancer therapeutics. Furthermore, experiments with these small molecules in vivo utilizing C.elegans demonstrate their additional utilization to aging studies. We observed that both molecules have the ability to induce a mitochondria-specific unfolded protein response (UPRMT) pathway, which extends lifespan of worms when applied in their adult stage. Interestingly, we also found that these two molecules employ different pathways to extend lifespan in worms, where MTZ utilize the transcription factors, ATFS-1 and HSF-1, which are involved in the UPRMT and heat shock response (HSR) pathways, respectively. In opposition,8-OAc only required HSF-1 and not ATFS-1. This observation elucidates an important insight into the functional roles of various protein subunits of ETC complexes and their regulatory mechanisms associated with aging.
Project description:We created a double loss-of-function/knockout mutant targeting two rice genes simultaneously. The selected genes are as follows: OsCNGC4(LOC_Os03g44440) and OsCNGC5(LOC_Os12g28260). These two CNGCs are strongly transcriptional expressed in the rice mature anthers (stages 13-14). The mutant of these OsCNGC4/5 displayed a low seed-setting rate. This data refers to the transcriptome of mature anthers from the double mutant of OsCNGC4 and OsCNGC5. We sampled mature anther for the analysis.
Project description:Rice anthers at anthesis stage from the wild type and osrac6-1 mutant anther (Dongjin cultivar) We collected the sample from our field and immediately froze the samples with liquid nitrogen.
Project description:Pollen tube growth is essential for successful fertilization and stable crop yields. We constructed loss-of-function/knock-out mutants that simultaneously target two rice genes using the CRISPR/Cas9 mutagenesis system. The selected OsRALF17 and OsRALF19 genes are strongly expressed in rice bicellular/tricellular pollen and have essential functions in the pollen tube growth. For the corresponding transcriptomic analysis, we sampled mature pollen anthers from a control group and an OsRALF17/19 knock-out mutant.
Project description:We created a triple loss-of-function/knockout mutant targeting three rice genes simultaneously. The three selected genes are as follows: OsADF1 (LOC_Os02g44470), OsADF6 (LOC_Os04g46910), and OsADF9 (LOC_Os07g30090). These three ADFs are strongly transcriptional expressed in the rice mature anthers (stages 13) and bi-/tricelluler pollen. The triple mutant of these OsADFs does not produce self-fertilizing seeds due to the short length of the pollen tube (male-sterile). This data is about mature anther transcriptome data about the triple mutant of OsADFs (ADFmT). We sampled mature anther for the analysis.
Project description:The capacity to deal with stress declines during the aging process, and preservation of cellular stress responses is critical to healthy aging. The unfolded protein response of the endoplasmic reticulum (UPRER) is one such conserved mechanism which is critical for the maintenance of several major functions of the ER during stress, including protein folding and lipid metabolism. Hyperactivation of the UPRER by overexpression of the major transcription factor, xbp-1s, solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissue to activate UPRER in a non-autonomous fashion. Previous work identified serotonergic and dopaminergic neurons in this signaling paradigm. To further expand our understanding of the neural circuitry that underlies the non-autonomous signaling of ER stress, we activated UPRER solely in glutamatergic, octopaminergic, and GABAergic neurons in C. elegans and paired whole-body transcriptomic analysis with functional assays. We found that UPRER-induced signals from glutamatergic neurons increased expression of canonical protein homeostasis pathways and octopaminergic neurons promoted pathogen response pathways, while minor, but statistically significant changes were observed in lipid metabolism-related genes with GABAergic UPRER activation. These findings provide further evidence for the distinct role neuronal subtypes play in driving the diverse response to ER stress.
Project description:Mechanical stress is a measure of internal resistance exhibited by a body or material when external forces, such as compression, tension, bending, etc. are applied. The study of mechanical stress on health and aging is a continuously growing field, as major changes to the extracellular matrix and cell-to-cell adhesions can result in dramatic changes to tissue stiffness during aging and diseased conditions. For example, during normal aging, many tissues including the ovaries, skin, blood vessels, and heart exhibit increased stiffness, which can result in a significant reduction in function of that organ. As such, numerous model systems have recently emerged to study the impact of mechanical and physical stress on cell and tissue health, including cell-culture conditions with matrigels and other surfaces that alter substrate stiffness and ex vivo tissue models that can apply stress directly to organs like muscle or tendons. Here, we sought to develop a novel method in an in vivo, model organism setting to study the impact of mechanical stress on aging, by increasing substrate stiffness in solid agar medium of C. elegans. To our surprise, we found shockingly limited impact of growth of C. elegans on stiffer substrates, including limited effects on cellular health, gene expression, organismal health, stress resilience, and longevity. Overall, our studies reveal that altering substrate stiffness of growth medium for C. elegans have only mild impact on animal health and longevity; however, these impacts were not nominal and open up important considerations for C. elegans biologists in standardizing agar medium choice for experimental assays.
Project description:Soil salinity is a major production constrain for agricultural crops, especially in Oryza sativa (rice). Analyzing physiological effect and molecular mechanism under salt stress is key for developing stress-tolerant plants. Roots system has a major role in coping with the osmotic change impacted by salinity and few salt-stress-related transcriptome studies in rice have been previously reported. However, transcriptome data sets using rice roots grown in soil condition are more relevant for further applications, but have not yet been available. The present work analyzed rice root and shoot physiological characteristics in response to salt stress using 250 mM NaCl for different timepoints. Subsequently, we identified that 5 day treatment is critical timepoint for stress response in the specific experimental design. We then generated RNA-Seq-based transcriptome data set with rice roots treated with 250 mM NaCl for 5 days along with untreated controls in soil condition using rice japonica cultivar Chilbo. We identified 447 upregulated genes under salt stress with more than fourfold changes (p value < 0.05, FDR < 0.05) and used qRT-PCR for six genes to confirm their salt-dependent induction patterns. GO-enrichment analysis indicated that carbohydrate and amino-acid metabolic process are significantly affected by the salt stress. MapMan overview analysis indicated that secondary metabolite-related genes are induced under salt stress. Metabolites profiling analysis confirmed that phenolics and flavonoids accumulate in root under salt stress. We further constructed a functional network consisting of regulatory genes based on predicted protein–protein interactions, suggesting useful regulatory molecular network for future applications.
Project description:The transcriptomic innate immune response derived from human nasal epithelial cells depends on how Streptococcus pneumoniae colonises the nasopharynx. This study compared three wild type strains and one deficient in pneumolysin to explore the pathways of epithelial activation following a three hour infection in vitro.