Highly Abundant Proteins Are Highly Thermostable.

Highly abundant proteins tend to evolve slowly (a trend called E-R anticorrelation), and a number of hypotheses have been proposed to explain this phenomenon. The misfolding avoidance hypothesis attributes the E-R anticorrelation to the abundance-dependent toxic effects of protein misfolding. To avoid these toxic effects, protein sequences (particularly those of highly expressed proteins) would be under selection to fold properly. One prediction of the misfolding avoidance hypothesis is that highly abundant proteins should exhibit high thermostability (i.e., a highly negative free energy of folding, ΔG). Thus far, only a handful of analyses have tested for a relationship between protein abundance and thermostability, producing contradictory results. These analyses have been limited by 1) the scarcity of ΔG data, 2) the fact that these data have been obtained by different laboratories and under different experimental conditions, 3) the problems associated with using proteins' melting energy (Tm) as a proxy for ΔG, and 4) the difficulty of controlling for potentially confounding variables. Here, we use computational methods to compare the free energy of folding of pairs of human-mouse orthologous proteins with different expression levels. Even though the effect size is limited, the most highly expressed ortholog is often the one with a more negative ΔG of folding, indicating that highly expressed proteins are often more thermostable.

The Codon Statistics Database: A Database of Codon Usage Bias.

We present the Codon Statistics Database, an online database that contains codon usage statistics for all the species with reference or representative genomes in RefSeq (over 15,000). The user can search for any species and access two sets of tables. One set lists, for each codon, the frequency, the Relative Synonymous Codon Usage, and whether the codon is preferred. Another set of tables lists, for each gene, its GC content, Effective Number of Codons, Codon Adaptation Index, and frequency of optimal codons. Equivalent tables can be accessed for (1) all nuclear genes, (2) nuclear genes encoding ribosomal proteins, (3) mitochondrial genes, and (4) chloroplast genes (if available in the relevant assembly). The user can also search for any taxonomic group (e.g., "primates") and obtain a table comparing all the species in the group. The database is free to access without registration at http://codonstatsdb.unr.edu.

Codon Usage Differences among Genes Expressed in Different Tissues of Drosophila melanogaster.

Codon usage patterns are affected by both mutational biases and translational selection. The frequency at which each codon is used in the genome is directly linked to the cellular concentrations of their corresponding tRNAs. Transfer RNA abundances-as well as the abundances of other potentially relevant factors, such as RNA-binding proteins-may vary across different tissues, making it possible that genes expressed in different tissues are subject to different translational selection regimes, and thus differ in their patterns of codon usage. These differences, however, are poorly understood, having been studied only in Arabidopsis, rice and human, with controversial results in human. Drosophila melanogaster is a suitable model organism to study tissue-specific codon adaptation given its large effective population size. Here, we compare 2,046 genes, each expressed specifically in one tissue of D. melanogaster. We show that genes expressed in different tissues exhibit significant differences in their patterns of codon usage, and that these differences are only partially due to differences in GC content, expression levels, or protein lengths. Remarkably, these differences are stronger when analyses are restricted to highly expressed genes. Our results strongly suggest that genes expressed in different tissues are subject to different regimes of translational selection.

Proteins of generalist and specialist pathogens differ in their amino acid composition.

Pathogens differ in their host specificities, with species infecting a unique host (specialist pathogens) and others having a wide host range (generalists). Molecular determinants of pathogen's host range remain poorly understood. Secreted proteins of generalist pathogens are expected to have a broader range of intermolecular interactions (i.e., higher promiscuity) compared with their specialist counterparts. We hypothesize that this increased promiscuity of generalist secretomes may be based on an elevated content of primitive amino acids and intrinsically disordered regions, as these features are known to increase protein flexibility and interactivity. Here, we measure the proportion of primitive amino acids and percentage of intrinsically disordered residues in secreted, membrane, and cytoplasmic proteins from pathogens with different host specificity. Supporting our prediction, there is a significant general enrichment for primitive amino acids and intrinsically disordered regions in proteins from generalists compared to specialists, particularly among secreted proteins in prokaryotes. Our findings support our hypothesis that secreted proteins' amino acid composition and disordered content influence the pathogens' host range.

Higher Rates of Protein Evolution in the Self-Fertilizing Plant Arabidopsis thaliana than in the Out-Crossers Arabidopsis lyrata and Arabidopsis halleri.

The common transition from out-crossing to self-fertilization in plants decreases effective population size. This is expected to result in a reduced efficacy of natural selection and in increased rates of protein evolution in selfing plants compared with their outcrossing congeners. Prior analyses, based on a very limited number of genes, detected no differences between the rates of protein evolution in the selfing Arabidopsis thaliana compared with the out-crosser Arabidopsis lyrata. Here, we reevaluate this trend using the complete genomes of A. thaliana, A. lyrata, Arabidopsis halleri, and the outgroups Capsella rubella and Thellungiella parvula. Our analyses indicate slightly but measurably higher nonsynonymous divergences (dN), synonymous divergences (dS) and dN/dS ratios in A. thaliana compared with the other Arabidopsis species, indicating that purifying selection is indeed less efficacious in A. thaliana.

Moyamoya in a non-Asian patient: a case report and review of the literature.

Moyamoya disease (MMD) has historically been diagnosed in the Japanese population. However, newer studies have demonstrated worldwide distribution. Of note, patients of Appalachian descent with no known Asian ancestry have presented with MMD. We are presenting a case of MMD in an Appalachian, non-Asian patient who presented to the neurosurgical service with a severe headache of four days duration. The patient was found to have multiple hemorrhagic infarcts on CT and was admitted to the ICU. Cerebral angiography findings confirmed the diagnosis of MMD. Our case provides information regarding signs and symptoms, diagnostic neuroimaging findings, and treatment modalities for MMD.

A split strap frame applicator for stereotactic frame placement.

BACKGROUND: Symmetric and orthogonal placement of stereotactic frames is an important part of many procedures. The authors describe a split strap frame applicator for stereotactic frame placement. METHODS: A strap was developed that uses 2 pairs of straps with a common center that support the weight of the frame during screw placement. Ear bars can be used to orient the frame. RESULTS: A retrospective review of the perioperative imaging of 20 patients revealed excellent frame placement with minimal deviation from orthogonal planes relative to the long axis of the head. CONCLUSION: The orienting usefulness of ear bars during frame placement can be used without the ear bars supporting the weight of the frame with this applicator.

Vagus nerve stimulation for chronic intractable hiccups. Case report.

Intractable hiccups are debilitating and usually a result of some underlying disease. Initial management includes vagal maneuvers and pharmacotherapy. When hiccups persist despite medical therapy, surgical intervention rarely is pursued. Cases described in the literature cite successful phrenic nerve blockade, crush injury, or percutaneous phrenic nerve pacing. The authors report on a case of intractable hiccups occurring after a posterior fossa stroke, Complete resolution of the spasms has been achieved to date following the placement of a vagus nerve stimulator.

Treatment of phenylketonuria-associated tremor with deep brain stimulation: case report.

OBJECTIVE AND IMPORTANCE: Phenylketonuria (PKU) is an inborn error of metabolism that causes severe neurological impairment, despite dietary treatment. We present a case of PKU-induced cerebellar tremor treated with deep brain stimulation. There have been no previously reported cases of a patient with a PKU tremor treated with deep brain stimulation. CLINICAL PRESENTATION: A 36-year-old male patient with PKU presented with signs of cerebellar disease including dysmetria, resting tremor, and intention tremor in the left upper extremity. INTERVENTION: A deep brain stimulation electrode was placed in the ventral intermediate nucleus of the right thalamus. CONCLUSION: Immediately after surgery, the patient had nearly complete resolution of intention tremor in the left arm. His resting tremor in the left hand was also greatly improved. The 30-month follow-up examination revealed maintenance of the immediate postoperative improvement.