Mining Time-delayed Gene Regulation Patterns from Gene Expression Data

Discovered gene regulation networks are very helpful to predict unknown gene functions. The activating and deactivating relations between genes and genes are mined from microarray gene expression data. There are evidences showing that multiple time units delay exist in a gene regulation process. Association rule mining technique is very suitable for finding regulation relations among genes. However, current association rule mining techniques cannot handle temporally ordered transactions. We propose a modified association rule mining technique for efficiently discovering time-delayed regulation relationships among genes.By analyzing gene expression data, we can discover gene relations. Thus, we use modified association rule to mine gene regulation patterns. Our proposed method, BC3, is designed to mine time-delayed gene regulation patterns with length 3 from time series gene expression data. However, the front two items are regulators, and the last item is their affecting target. First we use Apriori to find frequent 2-itemset in order to figure backward to BL1. The Apriori mined the frequent 2-itemset in the same time point, so we make the L2 split to length one for having relation in the same time point. Then we combine BL1 with L1 to a new ordered-set BC2 with time-delayed relations. After pruning BC2 with the threshold, BL2 is derived. The results are worked out by BL2 joining itself to BC3, and sifting BL3 from BC3. We use yeast gene expression data to evaluate our method and analyze the results to show our work is efficient

Oxylipin Signals Govern Drought And Salt Tolerance And Resistance To Pathogens

Lipid signals derived from lipoxygenases (LOX), called oxylipins, emerge as pivotal mediators in responses to environmental constraints including biotic and abiotic stresses. Anthracnose leaf blight and stalk rot caused by Colletotrichum graminicola are major diseases threatening corn production; drought and salinity severely devastate crop yield. The involvement of specific LOXs in defense responses to C. graminicola and tolerance to drought and salinity remain largely unknown. The first objective of this study was to elucidate the functions of dual-specific LOXs in defense against C. graminicola. The second objective aimed to test the hypothesis that LOXs regulate drought and salt stress tolerance in maize. Transposon-insertional mutants and near-isogenic wild type of several LOXs, 12-oxophytodienoic reductase (OPR), and ACC synthase (ACS) were utilized to investigate the oxylipin-mediated responses to C. graminicola, drought, and salinity. Results showed recombinant ZmLOX1 protein imparts both 13- and 9-LOX activities, a unique feature for plant LOX. Defense phytohormones, mechanical wounding, and Z-3-hexenal treatment significantly up-regulated ZmLOX1 and ZmLOX2 expression, suggesting roles in various stress responses. Disruption of these genes does not impair wound-induced JA biosynthesis. Genetic evidence is provided that disruption of ZmLOX1 or ZmLOX2 caused a significant decrease in resistance to C. graminicola in leaves that associated with lower benzoic acid (BA) and salicylic acid (SA) accumulation. By contrast, lox1-3 and lox2-1 mutants accumulated significantly higher level of SA, but lower 10-oxo-11-phytoenoic acid (10-OPEA) in stalks upon C. graminicola infection, resulting in increased resistance. These findings have shed light on understanding that these rare dual specific LOXs play a role in defense against pathogens. In this study, evidence is provided that ZmLOX2 is required for drought tolerance via regulating transpirational water loss, while ZmLOX4 promoted drought sensitivity. Metabolite profiling and RNA sequencing results suggest that oxylipins regulate maize drought tolerance by mediating JA biosynthesis pathway. Supporting this notion, a JA-deficient mutant opr7-5 opr8-2 displayed dramatic reduction in stomata aperture and transpirational water loss, indicating that JA serves to open stomata. Increased ET production of opr7-5 opr8-2 under drought stress is in agreement with higher transpiration of ET-deficient acs2 acs6 mutant, suggesting ET enhances stomatal closure. Excessive amounts of SA and 10-OPEA accumulation in lox1-3 correlated with increased sensitivity to salt stress. Collectively, these data suggest that oxylipin signals govern drought level of SA, but lower 10-oxo-11-phytoenoic acid (10-OPEA) in stalks upon C. graminicola infection, resulting in increased resistance. These findings have shed light on understanding that these rare dual specific LOXs play a role in defense against pathogens. In this study, evidence is provided that ZmLOX2 is required for drought tolerance via regulating transpirational water loss, while ZmLOX4 promoted drought sensitivity. Metabolite profiling and RNA sequencing results suggest that oxylipins regulate maize drought tolerance by mediating JA biosynthesis pathway. Supporting this notion, a JA-deficient mutant opr7-5 opr8-2 displayed dramatic reduction in stomata aperture and transpirational water loss, indicating that JA serves to open stomata. Increased ET production of opr7-5 opr8-2 under drought stress is in agreement with higher transpiration of ET-deficient acs2 acs6 mutant, suggesting ET enhances stomatal closure. Excessive amounts of SA and 10-OPEA accumulation in lox1-3 correlated with increased sensitivity to salt stress. Collectively, these data suggest that oxylipin signals govern drought and salt tolerance and resistance to pathogens

IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major nosocomial pathogen that is widespread in both health-care facilities and in the community at large, as a result of direct host-to-host transmission. Several virulence factors are associated with pathogen transmission to naive hosts. Immunodominant surface antigen B (IsaB) is a virulence factor that helps Staphylococcus aureus to evade the host defense system. However, the mechanism of IsaB on host transmissibility remains unclear. We found that IsaB expression was elevated in transmissible MRSA. Wild-type isaB strains inhibited autophagic flux to promote bacterial survival and elicit inflammation in THP-1 cells and mouse skin. MRSA isolates with increased IsaB expression showed decreased autophagic flux, and the MRSA isolate with the lowest IsaB expression showed increased autophagic flux. In addition, recombinant IsaB rescued the virulence of the isaB deletion strain and increased the group A streptococcus (GAS) virulence in vivo. Together, these results reveal that IsaB diminishes autophagic flux, thereby allowing MRSA to evade host degradation. These findings suggest that IsaB is a suitable target for preventing or treating MRSA infection

Regulation of axon repulsion by MAX-1 SUMOylation and AP-3.

During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5-mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5-mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3 Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3 Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3-mediated trafficking and degradation of UNC-5 receptors during axon guidance

Plexin-A3 and plexin-A4 restrict the migration of sympathetic neurons but not their neural crest precursors

AbstractDuring development, the semaphorin family of guidance molecules is required for proper formation of the sympathetic nervous system. Plexins are receptors that mediate semaphorin signaling, but how plexins function during sympathetic development is not fully understood. Using phenotypic analyses of mutant mice in vivo, expression pattern studies, and in vitro assays, we show that plexin-A3 and plexin-A4 are essential for normal sympathetic development. This study confirms our previous in vitro findings that the two plexins differentially regulate the guidance of sympathetic axons. In addition, we find that semaphorin signaling through plexin-A3 and plexin-A4 restricts the migration of sympathetic neurons, but these two plexins function redundantly since migration defects are only observed in plexin-A3/-A4 double mutants. Surprisingly, our analysis also indicates that plexin-A3 and plexin-A4 are not required for guiding neural crest precursors prior to reaching the sympathetic anlagen. Immunoprecipitation studies suggest that these two plexins independently mediate secreted semaphorin signaling. Thus, plexin-A3 and plexin-A4 are expressed in newly-differentiated sympathetic neurons, but not their neural crest precursors. They function cooperatively to regulate the migration of sympathetic neurons and then differentially to guide the sympathetic axons

Usability Assessment of a Cable-Driven Exoskeletal Robot for Hand Rehabilitation

Study design: Case series.Background: Robot-assisted rehabilitation mediated by exoskeletal devices is a popular topic of research. The biggest difficulty in the development of rehabilitation robots is the consideration of the clinical needs. This study investigated the usability of a novel cable-driven exoskeletal robot specifically designed for hand rehabilitation.Methods: The study consists of three steps, including prototype development, spasticity observation, and usability evaluation. First, we developed the prototype robot DexoHand to manipulate the patient's fingers based on the clinical needs and the cable-driven concept established in our previous work. Second, we applied DexoHand to patients with different levels of spasticity. Finally, we obtained the system usability scale (SUS) and assessed its usability.Results: Two healthy subjects were recruited in the pre-test, and 18 patients with stroke and four healthy subjects were recruited in the formal test for usability. The total SUS score obtained from the patients and healthy subjects was 94.77 ± 2.98 (n = 22), indicating an excellent level of usability. The satisfaction score was 4.74 ± 0.29 (n = 22), revealing high satisfaction with DexoHand. The tension profile measured by the cables showed the instantaneous force used to manipulate fingers among different muscle tone groups.Conclusions:DexoHand meets the clinical needs with excellent usability, satisfaction, and reliable tension force monitoring, yielding a feasible platform for robot-assisted hand rehabilitation