Cancer was recognized as a genetic disease at least four decades ago, with the realization that the spontaneous mutation rate must increase early in tumorigenesis, to account for the many mutations in tumor cells as compared with their progenitor normal cells. The genetic basis for cancer was established also from...
Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome’s integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced...
The BRAF proto-oncogene is a member of the Raf protein family that encodes serine/threonine protein kinases, which activate the MEK/ERK signaling transduction pathway. The V600E mutation of BRAF, found in 70% of melanoma cases, causes an upregulation of MEK/ERK signaling which leads to many hallmarks of cancer, including apoptosis evasion,...
RNA sequencing (RNA-seq) and genotyping-by-sequencing (GBS) were used for single nucleotide polymorphism (SNP) identification from two economically important obligate plant pathogens, Pseudoperonospora cubensis and P. humuli. Twenty isolates of P. cubensis and 19 isolates of P. humuli were genotyped using RNA-seq and GBS. Principle components analysis (PCA) of each data...
The chlamydiae are a family of obligate intracellular bacteria that have a unique bi-phasic developmental cycle, unique cellular properties, and a unique set of challenges to studying its biology. While genetic manipulation is becoming routine in Chlamydia, there are significant challenges to working with this intracellular parasite. The body of...
Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species (ROS) due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by PMN...
FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity,...
Mercury and arsenic are known developmental toxicants and environmental exposures are ubiquitous worldwide from natural and anthropogenic sources. Prenatal exposure to both contaminants are independently associated with adverse perinatal health outcomes and latent disease risk that could be in part mediated by epigenetic reprogramming events. Fetal programming events involving DNA...
Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically,...
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that...
The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of lowdose environmental mixtures and carcinogens in the promotion of invasion and metastasis...
Background:
Osteosarcoma (OS) is an aggressive and often fatal cancer that afflicts over 1000 humans and 10,000 dogs per year in the United States. Recent evidence suggests deregulation in the signaling triad, receptor activator of nuclear factor kappa B (RANK), its activating ligand (RANKL), and the RANKL inhibitor, osteoprotegerin (OPG)...
Polycyclic aromatic hydrocarbons (PAHs) and oxygen-substituted PAHs (OPAHs) are environmental contaminants present in urban air, dust, soil and water resulting from incomplete combustion of organic materials or fossil fuels; found in crude oil and coal; and formed through photoxidation or biotransformation of microbial. It is widely recognized that PAHs pose...
Genome defense likely evolved to curtail the spread of transposable elements and invading viruses. A combination of effective defense mechanisms has been shown to limit colonization of the Neurospora crassa genome by transposable elements. A novel DNA transposon named Sly1-1 was discovered in the genome of the most widely used...
Canine transitional cell carcinoma (TCC) has been shown to have a substantial inflammatory component. It exhibits genotypic and morphologic elements that resemble its human counterpart. Cyclooxygenases (COX) are key enzymes in the synthesis of proinflammatory molecules, such as prostaglandins. Excess prostaglandin production through cyclooxygenases may promote oncogenesis and progression of...
Peroxiredoxin (Prx) enzymes catalyze the reduction of hydrogen peroxide, peroxynitrous acid, and organic peroxides, and are extremely efficient peroxidases, with k[subscript cat]/K[subscript M] on the order of 10⁷ - 10⁸ M⁻¹ s⁻¹. Besides their role in oxidative stress defense, evidence has accumulated that some eukaryotes, including humans, use Prxs as...
Sporulation is an important strategy for certain bacterial species within the phylum Firmicutes to survive longer periods of time in adverse conditions. All spore-forming bacteria have two phases in their life; the vegetative form, where they can maintain all metabolic activities and replicate to increase numbers, and the spore form,...
Pseudoperonospora cubensis is an obligate pathogen and
causative agent of cucurbit downy mildew. To help advance
our understanding of the pathogenicity of P. cubensis, we
used RNA-Seq to improve the quality of its reference
genome sequence. We also characterized the RNA-Seq
dataset to inventory transcript isoforms and infer alternative
splicing...
A gene's duplication relaxes selection. Loss of duplicate, low-function DNA (fractionation) sometimes follows, mostly by deletion in plants, but mostly via the pseudogene pathway in fish and other clades with smaller population sizes. Subfunctionalization — the founding term of the Xfunctionalization lexicon — while not the general cause of differences...
Plant pathogenic Rhodococcus species are persistent pathogens able to cause severe growth deformities on a large range of hosts. The most well studied species, R. fascians is predicted by current models to synthesize a mixture of cytokinins that act to directly perturb the hosts' hormone balances, which results in abnormal...
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Figure 4.5. Average nucleotide identity dendogram for 59 isolates of
Rhodococcus