Digenic genotypes: The interface of inbreeding, linkage, and linkage disequilibrium.

Many traits in populations are well understood as being Mendelian effects at single loci or additive polygenic effects across numerous loci. However, there are important phenomena and traits that are intermediate between these two extremes and are known as oligogenic traits. Here we investigate digenic, or two-locus, traits and how their frequencies in populations are affected by non-random mating, specifically inbreeding, linkage disequilibrium, and selection.

Enhanced effective codon numbers to understand codon usage bias.

Codon usage bias is a well recognized phenomenon but the relative influence of its major causes: G+C content, mutational biases, and selection, are often difficult to disentangle. This paper presents methods to calculate modified effective codon numbers that allow the investigation of the sources of codon bias and how genes or organisms have their codon biases shaped. In particular, it demonstrates that variation in codon usage bias across organisms is likely driven more by likely mutational forces while the variation in codon usage bias within genomes is likely driven by codon selectional forces.

The nonlinear structure of linkage disequilibrium.

The allele frequency dependence of the ranges of all measures of linkage disequilibrium is well-known. The maximum values of commonly used parameters such as r and D vary depending on the allele frequencies at each locus. However, though this phenomenon is recognized and accounted for in many studies, the comprehensive mathematical framework underlying the limits of linkage disequilibrium measures at various frequency combinations is often heuristic or empirical.

Globin gene expression in correlation with G protein-related genes during erythroid differentiation.

Background: The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated potency for globin gene stimulation.

Stimulated stromal cells induce gamma-globin gene expression in erythroid cells via nitric oxide production.

Objective: We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies to demonstrate that stimulation of gamma-globin gene expression is also mediated by NOS induction in stromal cells within the bone marrow microenvironment.

Materials And Methods: Using NO analyzer, we measured NO production in endothelial and macrophage cell cultures.

Plant-mycorrhiza percent infection as evidence of coupled metabolism.

A common feature of mycorrhizal observation is the growth of the infection on the plant root as a percent of the infected root or root tip length. Often, this is measured as a logistic curve with an eventual, though usually transient, plateau. It is shown in this paper that the periods of stable percent infection in the mycorrhizal growth cycle correspond to periods where both the plant and mycorrhiza growth rates and likely metabolism are tightly coupled.

Patient note deidentification using a find-and-replace iterative process.

Medical research relies on access to clinical data. Health Insurance Portability and Accountability Act regulations require that patient information required for clinical research not have data that can be used to identify the patients from whose medical records the information has been derived. The only exception would be an institutional review board (IRB)-approved study for which the researcher has obtained a waiver to use patient data for a research study.

Biological activity of nitric oxide in the plasmatic compartment.

There exist reaction products of nitric oxide (NO) with blood that conserve its bioactivity and transduce an endocrine vasomotor function under certain conditions. Although S-nitrosated albumin has been considered the major species subserving this activity, recent data suggest that additional NO species, such as nitrite, nitrated lipids, N-nitrosamine, and iron-nitrosyl complexes, may contribute. We therefore examined the end products of NO reactions in plasma and blood in vitro and in vivo by using reductive chemiluminescent assays and electron paramagnetic resonance spectroscopy.

Exogenous reference RNA for normalization of real-time quantitative PCR.

We have utilized an in vitro transcribed 3' mRNA fragment of the plant gene ribulose bisphosphate carboxylase (RuBisCO) as an exogenous standard for normalization of quantitative PCR data. Both K562 cells and primary erythroid CD34+ progenitor cells were treated with sodium butyrate and changes in gamma-globin mRNA levels were assayed using a previously published TaqMan probe and primer set, while RuBisCO levels were assayed by a SYBR Green detection assay. The data presented show that a correction to measured gamma-globin induction was necessary with both cell types.

Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase.

Hydroxyurea treatment of patients with sickle-cell disease increases fetal hemoglobin (HbF), which reduces hemoglobin S polymerization and clinical complications. Despite its use in the treatment of myeloproliferative diseases for over 30 years, its mechanism of action remains uncertain. Recent studies have demonstrated that hydroxyurea generates the nitric oxide (NO) radical in vivo, and we therefore hypothesized that NO-donor properties might determine the hemoglobin phenotype.