Epigenetic Regulation of Salicylic Acid-Mediated Plant Defense

Plant pathogens remain a significant threat to the stability of modern agricultural systems, and the investigation of mechanisms to improve the security of food resources has led to the partial characterization of plant immune response. With this progress, there is a newfound ability to analyze the relative pathogen resistance capability of specifically modified organisms, and in doing so, it is possible to identify individual alterations that might play a role in creating a more robust immune response. In this study, ten Arabidopsis thaliana mutants were infiltrated with Pseudomonas syringae pv. morsprunorum alongside positive and negative control Col-0 Wild-Type and npr1-2. The infiltrated mutant varieties that showed resistance to the development of infection by the pathogen were then analyzed for their the NPR1 protein content and concentration of PR1 mRNA. The results of both studies provided evidence that the suvh456 and sir2-1 mutants had a more effective immune response than the positive control Wild-Type variety, which supported the indication of pathogen resistance noted by the infiltration assay. These proteins have epigenetic influence over gene expression, and can be said to be acting as negative regulators of Arabidopsis immune defense

Department of Music and Arts Technology's Music Therapy Program

poster abstractThe Music Therapy Program in the Department of Music and Arts Technology as two main goals: to improve the quality of life of individuals through the use of music-based interventions and to use rigorous, scientific methods to determine the best use of music-based interventions for individuals with medical and developmental needs

Inositol phosphorylceramide synthase null Leishmania are viable and virulent in animal infections where salvage of host sphingomyelin predominates

Many pathogens synthesize inositol phosphorylceramide (IPC) as the major sphingolipid (SL), differing from the mammalian host where sphingomyelin (SM) or more complex SLs predominate. The divergence between IPC synthase and mammalian SL synthases has prompted interest as a potential drug target. However, in the trypanosomatid protozoan Leishmania, cultured insect stage promastigotes lack de novo SL synthesis (Δspt

Absence of chloride intracellular channel 4 (CLIC4) predisposes to acute kidney injury but has minimal impact on recovery

BackgroundCLIC4, a member of the CLIC family of proteins, was recently demonstrated to translocate to the nucleus in differentiating keratinocytes where it potentiates TGFβ-driven gene regulation. Since TGFβ signaling is known to play important roles in the fibrotic response to acute kidney injury, and since CLIC4 is abundantly expressed in kidney, we hypothesized that CLIC4 may play a role in the response to acute kidney injury.MethodsPreviously described Clic4 null mice were analyzed for the effect of absence of CLIC4 on growth, development and response to kidney injury. Kidney size, glomerular counts and density of peritubular capillaries of matched WT and Clic4 null mice were determined. Cohorts of WT and Clic4 null mice were subjected to the folic acid model of acute kidney injury. Extent of acute injury and long term functional recovery were assessed by plasma blood urea nitrogen (BUN); long term fibrosis/scarring was determined by histochemical assessment of kidney sections and by residual renal mass. Activation of the TGFβ signaling pathway was assessed by semi-quantitative western blots of phosphorylated SMADs 2 and 3.ResultsCLIC4 is abundantly expressed in the apical pole of renal proximal tubule cells, and in endothelial cells of glomerular and peritubular capillaries. CLIC4 null mice are small, have smaller kidneys with fewer glomeruli and less dense peritubular capillary networks, and have increased proteinuria. The Clic4 null mice show increased susceptibility to folic acid-induced acute kidney injury but no difference in recovery from acute injury, no nuclear redistribution of CLIC4 following injury, and no significant difference in activation of the TGFβ-signaling pathway as reflected in the level of phosphorylation of SMADs 2 and 3.ConclusionsAbsence of CLIC4 results in morphologic changes consistent with its known role in angiogenesis. These changes may be at least partially responsible for the increased susceptibility to acute kidney injury. However, the absence of CLIC4 has no significant impact on the extent of functional recovery or fibrosis following acute injury, indicating that CLIC4 does not play a major non-redundant role in the TGFβ signaling involved in response to acute kidney injury

Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes

Type 2 diabetes is associated with insulin resistance, impaired pancreatic β-cell insulin secretion, and nonalcoholic fatty liver disease. Tissue-specific SWELL1 ablation impairs insulin signaling in adipose, skeletal muscle, and endothelium, and impairs β-cell insulin secretion and glycemic control. Here, we show that

Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA

From MDPI via Jisc Publications RouterHistory: accepted 2021-11-25, pub-electronic 2021-11-29Publication status: PublishedFunder: German Network for Mitochondrial Disorders; Grant(s): mitoNET, 01GM1906D, R01HL148153Funder: Action Medical Research; Grant(s): GN2494Funder: Office of the Assistant Secretary for Health; Grant(s): W81XWH-17-1-0052, W81XWH-20-1-0150Biallelic pathogenic variants in CLPP, encoding mitochondrial matrix peptidase ClpP, cause a rare autosomal recessive condition, Perrault syndrome type 3 (PRLTS3). It is characterized by primary ovarian insufficiency and early sensorineural hearing loss, often associated with progressive neurological deficits. Mouse models showed that accumulations of (i) its main protein interactor, the substrate-selecting AAA+ ATPase ClpX, (ii) mitoribosomes, and (iii) mtDNA nucleoids are the main cellular consequences of ClpP absence. However, the sequence of these events and their validity in human remain unclear. Here, we studied global proteome profiles to define ClpP substrates among mitochondrial ClpX interactors, which accumulated consistently in ClpP-null mouse embryonal fibroblasts and brains. Validation work included novel ClpP-mutant patient fibroblast proteomics. ClpX co-accumulated in mitochondria with the nucleoid component POLDIP2, the mitochondrial poly(A) mRNA granule element LRPPRC, and tRNA processing factor GFM1 (in mouse, also GRSF1). Only in mouse did accumulated ClpX, GFM1, and GRSF1 appear in nuclear fractions. Mitoribosomal accumulation was minor. Consistent accumulations in murine and human fibroblasts also affected multimerizing factors not known as ClpX interactors, namely, OAT, ASS1, ACADVL, STOM, PRDX3, PC, MUT, ALDH2, PMPCB, UQCRC2, and ACADSB, but the impact on downstream metabolites was marginal. Our data demonstrate the primary impact of ClpXP on the assembly of proteins with nucleic acids and show nucleoid enlargement in human as a key consequence

Degradation of Host Sphingomyelin Is Essential for Leishmania Virulence

In eukaryotes, sphingolipids (SLs) are important membrane components and powerful signaling molecules. In Leishmania, the major group of SLs is inositol phosphorylceramide (IPC), which is common in yeast and Trypanosomatids but absent in mammals. In contrast, sphingomyelin is not synthesized by Leishmania but is abundant in mammals. In the promastigote stage in vitro, Leishmania use SL metabolism as a major pathway to produce ethanolamine (EtN), a metabolite essential for survival and differentiation from non-virulent procyclics to highly virulent metacyclics. To further probe SL metabolism, we identified a gene encoding a putative neutral sphingomyelinase (SMase) and/or IPC hydrolase (IPCase), designated ISCL (Inositol phosphoSphingolipid phospholipase C-Like). Despite the lack of sphingomyelin synthesis, L. major promastigotes exhibited a potent SMase activity which was abolished upon deletion of ISCL, and increased following over-expression by episomal complementation. ISCL-dependent activity with sphingomyelin was about 20 fold greater than that seen with IPC. Null mutants of ISCL (iscl−) showed modest accumulation of IPC, but grew and differentiated normally in vitro. Interestingly, iscl− mutants did not induce lesion pathology in the susceptible BALB/c mice, yet persisted indefinitely at low levels at the site of infection. Notably, the acute virulence of iscl− was completely restored by the expression of ISCL or heterologous mammalian or fungal SMases, but not by fungal proteins exhibiting only IPCase activity. Together, these findings strongly suggest that degradation of host-derived sphingomyelin plays a pivotal role in the proliferation of Leishmania in mammalian hosts and the manifestation of acute disease pathology

The mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging

A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. Hence observation of these regions has wide application to understanding host-pathogen interactions. Interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with their unsupported membranes, invasive dissection can alter the tissue architecture. For these reasons, intravital imaging through the unperforated skull is the method of choice. We give a protocol for a simple method of two-photon microscopy through the thinned cortical skull of the anesthetized mouse to enable real-time imaging with sub-micron resolution through the meninges and into the superficial brain parenchyma. In reporter mice in which selected cell types express fluorescent proteins, imaging after infection with fluorescent pathogens (lymphocytic choriomeningitis virus, Trypanosoma brucei or Plasmodium berghei) has shown strong recruitment to the cortical meninges of immune cells, including neutrophils, T cells, and putative dendritic cells and macrophages. Without special labeling, the boundaries between the dura mater, the leptomeninx, and the parenchyma are not directly visualized in intravital two-photon microscopy, but other landmarks and characteristics, which we illustrate, allow the researcher to identify the compartment being imaged. While most infectious meningitides are localized mainly in the dura mater, others involve recruitment of immune cells to the leptomeninx