A5004535762- Renin-Angiotensin System Studies
- Receptor Mechanisms and Signaling
- Insect Resistance and Genetics
- Epigenetics and DNA Methylation
- Genetically Modified Organisms Research
- Insect and Pesticide Research
- Angiogenesis and VEGF in Cancer
- RNA Research and Splicing
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer-related gene regulation
- Mesenchymal stem cell research
- Insect-Plant Interactions and Control
- Congenital heart defects research
- Insect Pest Control Strategies
- Mitochondrial Function and Pathology
- Genomics, phytochemicals, and oxidative stress
- Cancer, Hypoxia, and Metabolism
- Hormonal Regulation and Hypertension
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Genetics and Neurodevelopmental Disorders
- Gene expression and cancer classification
Jackson Laboratory
2022-2024
Medical College of Wisconsin
2012-2022
Bioengineering Center
2015
Czech Academy of Sciences, Institute of Physiology
2011
University of Minnesota
2001-2010
The renin-angiotensin system plays an important role in the control of blood pressure (BP) and renal function. To illuminate importance renin context a disease background vivo, we used zinc-finger nucleases (ZFNs) designed to target gene create knockout SS/JrHsdMcwi (SS) rat. ZFN against caused 10-bp deletion exon 5, resulting frameshift mutation. Plasma activity was undetectable Ren-/- rat, protein absent from juxtaglomerular cells kidney. Body weight lower rats (than Ren+/- or wild-type...
Despite the striking differences between male and female physiology, physiology is understudied. In response, National Institutes of Health promulgating new policies to increase use organisms in preclinical research. Females are commonly believed have greater variability than males because estrous cycle, but recent studies call this belief into question. Effects cycling on mean arterial pressure were assessed Dahl S rats using telemetry vaginal cytometry found that did not affect magnitude...
The high-dose refuge resistance management strategy is the main approach used to delay in targeted pests Bacillus thuringiensis (Bt) toxins transgenic crops. We an F2 screen test a critical assumption of strategy, which that allele (R) frequencies are initially rare (<10(-3)) Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae) from southern Corn Belt. expanded methodological scope so both males and females may be initiate determined how results sexes combined. In total, 62 female 131 male...
Abstract Shortly after the discovery of endothelial progenitor cells (EPCs) in 1997, many clinical trials were conducted using EPCs as a cellular based therapy with goal restoring damaged organ function by inducing growth new blood vessels (angiogenesis). Results disappointing, largely because and molecular mechanisms EPC-induced angiogenesis not clearly understood. Following injection, must migrate to target tissue engraft prior induction angiogenesis. In this study EPC migration was...
The F2 screen is a flexible methodology used to estimate the frequency of resistance alleles (R) in an insect population. We have developed several alternative protocols, along with associated statistics, conduct mated or unmated individuals, random and nonrandom mating F1 adults, screening multiple lines together screen. Our protocols describe how perform analyze starting P1 as females. A randomly population ≥50 adults should be sufficient detect R <99% time. If occurs screen, it most...
The high-dose/refuge strategy is considered as the main for delaying resistance in target pests to genetically modified crops that produce insecticidal proteins derived from Bacillus thuringiensis Berliner. This based on a key assumption alleles are initially rare (<10(-3)). To test this assumption, we used an F2 screen natural populations of Sesamia nonagrioides Lefebvre (Lepidoptera: Noctuidae) Greece and Spain. In total, 75 lines 85 Spain were screened survival larvae Cry1Ab corn, Zea...
Angiotensin II (AngII) has been shown to regulate angiogenesis and at high pathophysiological doses cause vasoconstriction through the AngII receptor type 1. 1 7 (Ang-(1-7)) acting Mas1 can act antagonistically levels of by inducing vasodilation, whereas effects Ang-(1-7) signaling on are less defined. To complicate matter, there is growing evidence that a subpressor dose produces phenotypes similar Ang-(1-7).This study shows low-dose Ang-(1-7), receptor, promotes vasodilation low, In...
The high-dose refuge resistance management strategy is the main approach used to delay in targeted pests Bacillus thuringiensis (Bt) toxins transgenic crops. We an F2 screen test a critical assumption of strategy, which that allele (R) frequencies are initially rare (<10−3) Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae) from southern Corn Belt. expanded methodological scope so both males and females may be initiate determined how results sexes combined. In total, 62 female 131 male O....
The large-scale cultivation of transgenic crops producing Bacillus thuringiensis (Bt) toxins have already lead to the evolution Bt resistance in some pest populations targeted by these crops. We used F2 screening method for further estimating frequency alleles European corn borer, Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae), maize, Zea mays L., Cry1Ab toxin. In France, Germany, and Italy, 784, 455, 80 lines borer were screened Mon810 respectively. Slovakia, 26 cost screen performed...
Autologous bone marrow cell (BMC) transplantation has been shown as a potential approach to treat various ischemic diseases. However, under many conditions BMC dysfunction reported, leading poor engraftment and failure of tissue revascularization. We have previously that skeletal muscle angiogenesis induced by electrical stimulation (ES) is impaired in the SS/Mcwi rats this effect related dysregulation renin angiotensin system (RAS) normalized replacement chromosome 13 derived from Brown...
Endothelial progenitor cells (EPCs) promote angiogenesis, and clinical trials suggest autologous EPC-based therapy may be effective in treatment of vascular diseases. Albeit promising, variability the efficacy EPCs associated with underlying disease states has hindered realization therapy. Here we first identify characterize EPC dysfunction a rodent model (SS/Mcwi rat) that exhibits impaired angiogenesis. To molecular candidates mediate angiogenic potential these cells, performed broad...
The histone demethylase KDM6A has recently elicited significant attention because its mutations are associated with a rare congenital disorder (Kabuki syndrome) and various types of human cancers. However, distinguishing that deleterious to the enzyme their underlying mechanisms dysfunction remain be fully understood. Here, we report results from multi-tiered approach evaluating impact 197 somatic using information derived combining conventional genomics data computational biophysics. This...
Abstract Vegetational diversity in agricultural systems is predicted to reduce herbivore populations, but we observed the opposite effect: higher nymph population densities of a functionally monophagous herbivore, squash bug, Anasa tristis (Hemiptera: Coreidae) vegetationally diverse squash‐bean‐corn polyculture than monoculture. We examined spatial and temporal aspects bug predator populations relation vegetational diversity. Average colonization, oviposition, mortality rates for were...
Abstract Background Kabuki syndrome is a genetic disorder that affects several body systems and presents with variations in symptoms severity. The named for common phenotype of faces resembling stage makeup used Japanese traditional theatrical art kabuki . most frequent cause this mutations the H3K4 family histone methyltransferases while smaller percentage results from alterations affecting demethylase, KDM6A. Because rare presentation latter form disease, little known about how missense...
Pancreatic ductal adenocarcinoma initiation is most frequently caused by Kras mutations. Here, we apply biological, biochemical, and network biology methods to validate GEMM-derived cell models using inducible KrasG12D expression. We describe the time-dependent, chromatin remodeling program that impacts function during early oncogenic signaling. find KrasG12D-induced transcriptional response dominated downregulated expression concordant with layers of epigenetic events. More open...
The health risks that arise from environmental exposures vary widely within and across human populations, these differences are largely determined by genetic variation gene-by-environment (gene–environment) interactions. However, risk assessment in laboratory mice typically involves isogenic strains therefore, does not account for known effects. In this context, genetically heterogenous cell lines promising tools population-based screening because they provide a way to introduce without...
Bone marrow mononuclear cells (BMMNCs) increase capillary density and reduce fibrosis in rodents after myocardial infarction, resulting an overall improvement left ventricular function. Little is known about the effectiveness of BMMNC therapy hypertensive heart disease. In current study, we show that delivery BMMNCs from hypertension protected SS-13 BN /MCWi donor rats, but not susceptible SS/MCWi resulted 57.2 83.4% reductions perivascular interstitial fibrosis, respectively, as well a 60%...
Abstract NADK2 encodes the mitochondrial form of nicotinamide adenine dinucleotide (NAD) kinase, which phosphorylates NAD. Rare recessive mutations in human are associated with a syndromic neurological disease that includes metabolic changes, such as hyperlysinemia and 2,4 dienoyl CoA reductase (DECR) deficiency. However, full pathophysiology resulting from deficiency is not known. Here, we describe two chemically induced mouse Nadk2—S326L S330P—which cause severe neuromuscular shorten...
Impaired regulation of renin in Dahl salt-sensitive rats (SS/JRHsdMcwi, SS) contributes to attenuated angiogenesis this strain. This study examined angiogenic function and genomic structure regions surrounding the gene using subcongenic strains SS BN/NHsdMcwi (BN) rat identify important variations between BN involved angiogenesis. Three candidate on Chr 13 were studied: two congenic containing 0.89 2.62 Mb portions that excluded allele a third strain contained 2.02 overlapping region...
The heptapeptide angiotensin-(1–7) (Ang-(1–7)) is protective in the cardiovascular system through its induction of vasodilator production and angiogenesis. Despite acting antagonistically to effects elevated, pathophysiological levels angiotensin II (AngII), recent evidence has identified convergent beneficial low both Ang-(1–7) AngII. Previous work AngII receptor type I (AT1R) as a component protein complex formed when binds receptor, Mas1. Importantly, pharmacological blockade AT1R did not...
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, painful disease with a 5-year survival rate of only 9%. Recent evidence indicates that distinct epigenomic landscapes underlie PDAC progression, identifying the H3K9me pathway as important to its pathobiology. Here, we delineate role Euchromatic Histone-lysine N-Methyltransferase 2 (EHMT2), enzyme generates H3K9me, downstream effector oncogenic KRAS during initiation and pancreatitis-associated promotion. EHMT2 inactivation in...
A challenge to understanding enhancer-gene relationships is that enhancers are not always sequentially close the gene they regulate. Physical proximity mapping through sequencing can provide an unbiased view of chromatin proximal promoter renin ( Ren). Our objective was determine genomic regions physically interact with promoter, using two different genetic backgrounds, Dahl salt sensitive and normotensive SS-13BN, which have been shown regulation plasma in vivo. The conformation capture...
A wheat germ-casien-agar diet for rearing European corn borer, Ostrinia nubilalis Hübner, contains five preservatives, sorbic acid (0.055% w/w), para-hydroxybenzoic methyl ester (methyl paraben, 0.144% propionic (0.488% aureomycin (0.292% and phosphoric (0.084% w/w). We conducted studies to determine if the first four of these preservatives can be reduced. In experiment we eliminated simultaneously either retained all paraben or reduced them by 50% as well. The with full no performed similar...