Spray-induced gene silencing to identify powdery mildew gene targets and processes for powdery mildew control.

Spray-induced gene silencing (SIGS) is an emerging tool for crop pest protection. It utilizes exogenously applied double-stranded RNA to specifically reduce pest target gene expression using endogenous RNA interference machinery. In this study, SIGS methods were developed and optimized for powdery mildew fungi, which are widespread obligate biotrophic fungi that infect agricultural crops, using the known azole-fungicide target cytochrome P450 51 (CYP51) in the Golovinomyces orontii-Arabidopsis thaliana pathosystem.

Conditional Ablation of Glucocorticoid and Mineralocorticoid Receptors from Cochlear Supporting Cells Reveals Their Differential Roles for Hearing Sensitivity and Dynamics of Recovery from Noise-Induced Hearing Loss.

Endogenous glucocorticoids (GC) are known to modulate basic elements of cochlear physiology. These include both noise-induced injury and circadian rhythms. While GC signaling in the cochlea can directly influence auditory transduction via actions on hair cells and spiral ganglion neurons, evidence also indicates that GC signaling exerts effects via tissue homeostatic processes that can include effects on cochlear immunomodulation.

Detection of West Nile Virus Envelope Protein in Brain Tissue with an Immunohistochemical Assay.

Immunohistochemistry is a valuable tool for probing not only scientific questions but also clinical diagnoses. It provides power from localization of a protein within the milieu of a tissue section that may reflect positioning within or beyond the boundaries of a cell that is representative of the tissue at a discrete moment in time. The method can be applied broadly, including to tissues under normal, developmental, chemically, or genetically altered conditions and disease states.

Zika virus infection causes widespread damage to the inner ear.

Zika virus (ZIKV) has been recently recognized as a causative agent of newborn microcephaly, as well as other neurological consequences. A less well recognized comorbidity of prenatal ZIKV infection is hearing loss, but cases of hearing impairment following adult ZIKV infection have also been recognized. Diminished hearing following prenatal ZIKV infection in a mouse model has been reported, but no cellular consequences were observed.

Deletion of nicotinic acetylcholine receptor alpha9 in mice resulted in altered bone structure.

Alterations in bone strength and structure were found in knockout (KO) mouse strains with deletion of several acetylcholine receptors. Interestingly, the expression of the nicotinic acetylcholine receptors (nAChR) subunit α10 was down-regulated in osteogenic differentiated mesenchymal stem cells of patients with osteoporosis whereas the expression of subunit α9 was not altered. Since nAChR subunits α9 and α10 are often combined in a functional receptor, we analyzed here the bone of adult female KO mice with single deletion of either nAChR alpha9 (α9KO) or alpha10 (α10KO).

Cellular and axonal constituents of neocortical molecular layer heterotopia.

Human neocortical molecular layer heterotopia consist of aggregations of hundreds of neurons and glia in the molecular layer (layer I) and are indicative of neuronal migration defect. Despite having been associated with dyslexia, epilepsy, cobblestone lissencephaly, polymicrogyria, and Fukuyama muscular dystrophy, a complete understanding of the cellular and axonal constituents of molecular layer heterotopia is lacking. Using a mouse model, we identify diverse excitatory and inhibitory neurons as well as glia in heterotopia based on molecular profiles.

PIAS1 regulates breast tumorigenesis through selective epigenetic gene silencing.

Epigenetic gene silencing by histone modifications and DNA methylation is essential for cancer development. The molecular mechanism that promotes selective epigenetic changes during tumorigenesis is not understood. We report here that the PIAS1 SUMO ligase is involved in the progression of breast tumorigenesis.

PIAS1 SUMO ligase regulates the self-renewal and differentiation of hematopoietic stem cells.

The selective and temporal DNA methylation plays an important role in the self-renewal and differentiation of hematopoietic stem cells (HSCs), but the molecular mechanism that controls the dynamics of DNA methylation is not understood. Here, we report that the PIAS1 epigenetic pathway plays an important role in regulating HSC self-renewal and differentiation. PIAS1 is required for maintaining the quiescence of dormant HSCs and the long-term repopulating capacity of HSC.

β2 and γ3 laminins are critical cortical basement membrane components: ablation of Lamb2 and Lamc3 genes disrupts cortical lamination and produces dysplasia.

Cortical development is dependent on the timely production and migration of neurons from neurogenic sites to their mature positions. Mutations in several receptors for extracellular matrix (ECM) molecules and their downstream signaling cascades produce dysplasia in brain. Although mutation of a critical binding site in the gene that encodes the ECM molecule laminin γ1 (Lamc1) disrupts cortical lamination, the ECM ligand(s) for many ECM receptors have not been demonstrated directly in the cortex.

Schizophrenia susceptibility pathway neuregulin 1-ErbB4 suppresses Src upregulation of NMDA receptors.

Hypofunction of the N-methyl D-aspartate subtype of glutamate receptor (NMDAR) is hypothesized to be a mechanism underlying cognitive dysfunction in individuals with schizophrenia. For the schizophrenia-linked genes NRG1 and ERBB4, NMDAR hypofunction is thus considered a key detrimental consequence of the excessive NRG1-ErbB4 signaling found in people with schizophrenia. However, we show here that neuregulin 1β-ErbB4 (NRG1β-ErbB4) signaling does not cause general hypofunction of NMDARs.

The ligase PIAS1 restricts natural regulatory T cell differentiation by epigenetic repression.

CD4(+)Foxp3(+) regulatory T (T(reg)) cells are important for maintaining immune tolerance. Understanding the molecular mechanism that regulates T(reg) differentiation will facilitate the development of effective therapeutic strategies against autoimmune diseases. We report here that the SUMO E3 ligase PIAS1 restricts the differentiation of natural T(reg) cells by maintaining a repressive chromatin state of the Foxp3 promoter.

Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism.

Maintenance of single-layered endothelium, squamous endothelial cell shape, and formation of a patent vascular lumen all require defined endothelial cell polarity. Loss of beta1 integrin (Itgb1) in nascent endothelium leads to disruption of arterial endothelial cell polarity and lumen formation. The loss of polarity is manifested as cuboidal-shaped endothelial cells with dysregulated levels and mislocalization of normally polarized cell-cell adhesion molecules, as well as decreased expression of the polarity gene Par3 (pard3).

A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.

Loss of the CDK inhibitor p27(KIP1) is widely linked with poor prognosis in human cancer. In Wnt10b-expressing mammary tumors, levels of p27(KIP1) were extremely low; conversely, Wnt10b-null mammary cells expressed high levels of this protein, suggesting Wnt-dependent regulation of p27(KIP1). Interestingly we found that Wnt-induced turnover of p27(KIP1) was independent from classical SCF(SKP2)-mediated degradation in both mouse and human cells.

Heparin-binding EGF-like growth factor shows transient left-right asymmetrical expression in mouse myotome pairs.

Heparin-binding EGF-like growth factor (HB-EGF) is a potent mitogen and chemoattractant for diverse cell types including, keratinocytes, fibroblasts and vascular smooth muscle cells. In adult mice, skeletal muscle and endothelial cells prominently express HB-EGF, although analysis of embryonic expression has been limited to studies of heart and kidney development. Here we survey HB-EGF mRNA expression in E7.

Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4.

We have recently described an IFN regulatory factor 3-mediated antiviral gene program that is induced by both Toll-like receptor (TLR)3 and TLR4 ligands. In our current study, we show that activation of IFN/viral response gene expression in primary macrophage cells is stronger and prolonged with TLR3 stimulation compared with that of TLR4. Our data also reveal that the cytoplasmic tails of both TLR3 and TLR4 can directly interact with myeloid differentiation factor 88 (MyD88).