American Indians without tribes in the twenty-first century

Among American Indians and Alaska Natives, most aspects of ethnicity are tightly associated with the person's tribal origins. Language, history, foods, land and traditions differ among the hundreds of tribes indigenous to the USA. With this in mind, we ask why almost one million American Indians failed to respond to the tribal affiliation part of the Census 2000 race question. We investigate four hypotheses about why one-third of multiracial American Indians and one-sixth of single-race American Indians did not write any response to the tribal affiliation question: (1) survey item non-response that undermines all fill-in-the-blank questions; (2) a non-salient tribal identity; (3) a genealogy-based affiliation; and (4) a mestizo identity, which does not require a tribe. We use multivariate logistic regression models and high-density restricted-use Census 2000 data. We find support for the first two hypotheses and note that predictors differ substantially for single-race versus multiple-race American Indians.     

Iron Acquisition from Natural Organic Matter by an Aerobic Pseudomonas mendocina Bacterium: Siderophores and Cellular Iron Status

This research investigated the potential role of siderophores in aerobic microbial Fe acquisition from natural organic matter (NOM; XAD-8 isolate and reverse osmosis concentrate pre- and post-Chelex® treatment) through the use of a siderophore-producing Pseudomonas mendocina wild type (WT) bacterium and an engineered mutant (Mt) that was incapable of siderophore production. NOM had complex effects on microbial growth under Fe-limited conditions as measured by optical density, most likely because of the presence of other toxic (trace) metals such as Al, NOM binding interference with additional trace metal nutrients, and/or biofilm development. However, a bioassay for cellular Fe status showed that both WT and Mt readily acquired Fe naturally associated with NOM. Thus, while siderophores may be useful for Fe acquisition from NOM by P. mendocina, they do not appear to be essential for this process.     

Binding and transport of PAMAM-RGD in a tumor spheroid model: the effect of RGD targeting ligand density

The mechanisms governing the efficient tumor spheroid penetration and transport by poly(amidoamine) (PAMAM) dendrimers displaying varying numbers of cyclic RGD targeting peptides (2, 3, 7, or 10) were evaluated in this work. The cell-free binding affinities and cellular internalization kinetics of PAMAM-RGD conjugates to malignant glioma cells were determined experimentally, and the results were incorporated into a mathematical model to predict the transport of these materials through a multicellular tumor spheroid. The theoretical analysis demonstrated that greater RGD crosslinking may improve transport through tumor spheroids due to their decreased integrin-binding affinity. This study provides evidence that altering the density of tumor-targeting ligands from a drug delivery platform is a feasible way to optimize the tumor-penetration efficiency of an anticancer agent, and provides insight into the physicochemical mechanisms governing the relative effectiveness of these conjugates.     

NMR assignments for the telokin-like domain of bacteriophage P22 coat protein

The bacteriophage P22 virion is assembled from identical coat protein monomers in a complex reaction that is generally conserved among tailed, double-stranded DNA bacteriophages and viruses. Many coat proteins of dsDNA viruses have structures based on the HK97 fold, but in some viruses and phages there are additional domains. In the P22 coat protein, a “telokin-like” domain was recently identified, whose structure has not yet been characterized at high-resolution. Two recently published low-resolution cryo-EM reconstructions suggest markedly different folds for the telokin-like domain that lead to alternative conclusions about its function in capsid assembly and stability. Here we report ¹H, ¹⁵N, and ¹³C NMR resonance assignments for the telokin-like domain. The secondary structure predicted from the chemical shift values obtained in this work shows significant discrepancies from both cryo-EM models but agrees better with one of the models. In particular, the functionally important “D-loop” in one model shows chemical shifts and solvent exchange protection more consistent with β-sheet structure. Our work will set the basis for a high-resolution NMR structure determination of the telokin-like domain that will help improve the cryo-EM models, and in turn lead to a better understanding of how coat protein monomers assemble into the icosahedral capsids required for virulence.     

Understanding deficient emotional self-regulation in adults with attention deficit hyperactivity disorder: a controlled study

While symptoms of deficient emotional self-regulation (DESR) such as low frustration tolerance, temper outbursts, emotional impulsivity, and mood lability are commonly associated with attention deficit hyperactivity disorder (ADHD), little is known about their nature. The main aim of this post hoc study was to examine the correlates of DESR in a large sample of adults with and without ADHD. Subjects were 206 adults with ADHD and 123 adults without ADHD from a family study of ADHD. Emotional impulsivity was operationalized using items from the Barkley Current Behavior Scale. Subjects were comprehensively assessed for psychiatric comorbidity using structured diagnostic interview methodology. We used the Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form (QLES-Q-SF) and Social Adjustment Scale-Self-report (SAS-SR) to assess quality of life and psychosocial functioning. DESR was more common among ADHD compared with non-ADHD adults, and 55 % of adults with ADHD reported extreme DESR of greater severity than 95 % of control subjects. The association of ADHD and DESR was not entirely accounted for by either current or lifetime comorbid disorders. DESR was also associated with significant functional impairment as evaluated by the QLES-Q-SF and SAS-SR, and with reduced marital status, as well as higher risk for traffic accidents and arrests. DESR adversely impacts quality of life in adults with ADHD. More work is needed to further evaluate DESR in clinical and investigational studies of subjects with ADHD.     

Candidate Sequence Variants and Fetal Hemoglobin in Children with Sickle Cell Disease Treated with Hydroxyurea

Background

Fetal hemoglobin level is a heritable complex trait that strongly correlates swith the clinical severity of sickle cell disease. Only few genetic loci have been identified as robustly associated with fetal hemoglobin in patients with sickle cell disease, primarily adults. The sole approved pharmacologic therapy for this disease is hydroxyurea, with effects largely attributable to induction of fetal hemoglobin.

Methodology/Principal Findings

In a multi-site observational analysis of children with sickle cell disease, candidate single nucleotide polymorphisms associated with baseline fetal hemoglobin levels in adult sickle cell disease were examined in children at baseline and induced by hydroxyurea therapy. For baseline levels, single marker analysis demonstrated significant association with BCL11A and the beta and epsilon globin loci (HBB and HBE, respectively), with an additive attributable variance from these loci of 23%. Among a subset of children on hydroxyurea, baseline fetal hemoglobin levels explained 33% of the variance in induced levels. The variant in HBE accounted for an additional 13% of the variance in induced levels, while variants in the HBB and BCL11A loci did not contribute beyond baseline levels.

Conclusions/Significance

These findings clarify the overlap between baseline and hydroxyurea-induced fetal hemoglobin levels in pediatric disease. Studies assessing influences of specific sequence variants in these and other genetic loci in larger populations and in unusual hydroxyurea responders are needed to further understand the maintenance and therapeutic induction of fetal hemoglobin in pediatric sickle cell disease.