Evaluation of the authenticity of a highly novel environmental sequence from boreal forest soil using ribosomal RNA secondary structure modeling.

The number of sequences from both formally described taxa and uncultured environmental DNA deposited in the International Nucleotide Sequence Databases has increased substantially over the last two decades. Although the majority of these sequences represent authentic gene copies, there is evidence of DNA artifacts in these databases as well. These include lab artifacts, such as PCR chimeras, and biological artifacts such as pseudogenes or other paralogous sequences. Sequences that fall in basal positions in phylogenetic trees and appear distant from known sequences are particularly suspect. Phylogenetic analyses suggest that a novel sequence type (NS1) found in two boreal forest soil clone libraries belongs to the fungal kingdom but does not fall unambiguously within any known phylum. We have evaluated this sequence type using an array of secondary-structure analyses. To our knowledge, such analyses have never been used on environmental ribosomal sequences. Ribosomal secondary structure was modeled for four rRNA loci (ITS1, 5.8S, ITS2, 5' LSU). These models were analyzed for the presence of conserved domains, conserved nucleotide motifs, and compensatory base changes. Minimal free energy (MFE) foldings and GC contents of sequences representing the major fungal clades, as well as NS1, were also compared. NS1 displays secondary rRNA structures consistent with other fungi and many, but not all, conserved nucleotide motifs found across eukaryotes. However, our analyses show that many other authentic sequences from basal fungi lack more of these conserved motifs than does NS1. Together our findings suggest that NS1 represents an authentic gene copy. The methods described here can be used on any rRNA-coding sequence, not just environmental fungal sequences. As new-generation sequencing methods that yield shorter sequences become more widely implemented, methods that evaluate sequence authenticity should also be more widely implemented. For fungi, the adjacent 5.8S and ITS2 loci should be prioritized. This region is not only suited to distinguishing between closely related species, but it is also more informative in terms of expected secondary structure.

Some evolutionary perspectives on Alzheimer's disease pathogenesis and pathology.

There is increasing urgency to develop effective prevention and treatment for Alzheimer's disease (AD) as the aging population swells. Yet, our understanding remains limited for the elemental pathophysiological mechanisms of AD dementia that may be causal, compensatory, or epiphenomenal. To this end, we consider AD and why it exists from the perspectives of natural selection, adaptation, genetic drift, and other evolutionary forces. We discuss the connection between the apolipoprotein E (APOE) allele and AD, with special consideration to APOE ɛ4 as the ancestral allele. The phylogeny of AD-like changes across species is also examined, and pathology and treatment implications of AD are discussed from the perspective of evolutionary medicine. In particular, amyloid-ß (Aß) neuritic plaques and paired helical filament tau (PHFtau) neurofibrillary tangles have been traditionally viewed as injurious pathologies to be targeted, but may be preservative or restorative processes that mitigate harmful neurodegenerative processes or may be epiphenoma of the essential processes that cause neurodegeneration. Thus, we raise fundamental questions about current strategies for AD prevention and therapeutics.

PsychTable.org: A tool for biopolitical researchers, policymakers, and citizens.

PsychTable.org is a new online, mass-collaborative tool for the social sciences that aggregates evidence for and classifies the evolved psychological adaptations (EPAs) that have been proposed to comprise the human mind. This article provides an overview of the need for this reference tool and how it can benefit researchers who incorporate the behavioral sciences into their work. The article walks the reader through a hypothetical use case for PsychTable.org and describes the features of the website. PsychTable.org is intended to help key stakeholders better understand the linkages between EPAs and political behavior, public policy, and ethics.

The understanding and experience of mixed emotions in 3-5-year-old children.

The term mixed emotions refers to the presence of two opposite-valence emotions toward a single target. Identifying when children begin to report experiencing and understanding mixed emotions is critical in identifying how skills such as adaptive functioning, coping strategies, environmental understanding, and socioemotional competence emerge. Prior research has shown that children as young as 5 years old can understand and experience mixed emotion, but perhaps appropriately sensitive methodologies can reveal these abilities in younger children. The present study evaluated 57 children between 3 and 5 years old for mixed emotion experience and understanding using an animated video clip in which a character experiences a mixed emotional episode. Ordinal logistic regression was utilized to examine the relation of gender, attention, and understanding of content to experience and understanding of mixed emotion. While only 12% of children reported experiencing mixed emotion while watching the clip, 49% of children-some as young as 3 years old-were able to recognize the mixed emotional experience of the character. Thus, mixed emotion understanding emerges earlier than previously identified and the expression of understanding may develop independently of the ability to report mixed emotion experience. These findings are discussed in relation to cognitive and developmental considerations.

Assessing satisfaction with desloratadine and fexofenadine in allergy patients who report dissatisfaction with loratadine.

BACKGROUND: The FDA recently moved loratadine (Claritin) from prescription only status to over-the-counter (OTC). In response to the availability of an OTC non-sedating antihistamine, many managed care organizations are reevaluating which if any prescription antihistamines should remain on formulary. From a managed care perspective, determining which of the remaining prescription antihistamines results in the greatest patient satisfaction with allergy treatment would be informative. METHODS: We report on a weighted cross sectional survey (n = 10,023) delivered online to a sample of allergy sufferers in the U.S. during the month of December 2002. Two segments were identified for analysis: patient who were dissatisfied with loratadine and converted to desloratadine (Clarinex; n = 61), and patients who were dissatisfied with loratadine and converted to fexofenadine (Allegra; n = 211). The two segments were compared along a series of measures that the literature suggests are related to treatment satisfaction. RESULTS: The survey found that two of the satisfaction measures differentiated desloratadine converters from fexofenadine converters (p <.05): mean sum of self-reported adverse events and nighttime awakening due to allergy symptoms. For the remainder of satisfaction measures though, patients who were dissatisfied with loratadine reported equal duration of coverage and satisfaction with desloratadine as fexofenadine. When severity of disease was controlled for in the analysis, a pattern emerged suggesting greater levels of satisfaction amongst loratadine dissatisfied patients who converted to desloratadine. Point estimates suggest a consistent pattern favoring desloratadine patient satisfaction, with statistically significant results reported for sum of adverse effects, nighttime awakening due to symptoms, symptom severity just prior to the next dose, and overall satisfaction (p < 0.05). CONCLUSIONS: On average, patients who were dissatisfied with loratadine reported equal or better satisfaction with desloratadine as fexofenadine. Patients with severe allergic rhinitis reported greater satisfaction when converted from loratadine to desloratadine than fexofenadine for select satisfaction measures. These results suggest that if managed care intends to position prescription antihistamines as second line for OTC loratadine treatment dissatisfaction, desloratadine is a useful treatment alternative. These findings, while informative to formulary decision-makers, must be interpreted with caution. Only through head-to-head controlled clinical trials can differences in efficacy and safety be established.