Dynamic evolution of the alpha (α) and beta (β) keratins has accompanied integument diversification and the adaptation of birds into novel lifestyles.

BACKGROUND: Vertebrate skin appendages are constructed of keratins produced by multigene families. Alpha (α) keratins are found in all vertebrates, while beta (β) keratins are found exclusively in reptiles and birds. We have studied the molecular evolution of these gene families in the genomes of 48 phylogenetically diverse birds and their expression in the scales and feathers of the chicken. RESULTS: We found that the total number of α-keratins is lower in birds than mammals and non-avian reptiles, yet two α-keratin genes (KRT42 and KRT75) have expanded in birds. The β-keratins, however, demonstrate a dynamic evolution associated with avian lifestyle. The avian specific feather β-keratins comprise a large majority of the total number of β-keratins, but independently derived lineages of aquatic and predatory birds have smaller proportions of feather β-keratin genes and larger proportions of keratinocyte β-keratin genes. Additionally, birds of prey have a larger proportion of claw β-keratins. Analysis of α- and β-keratin expression during development of chicken scales and feathers demonstrates that while α-keratins are expressed in these tissues, the number and magnitude of expressed β-keratin genes far exceeds that of α-keratins. CONCLUSIONS: These results support the view that the number of α- and β-keratin genes expressed, the proportion of the β-keratin subfamily genes expressed and the diversification of the β-keratin genes have been important for the evolution of the feather and the adaptation of birds into multiple ecological niches.

EPR spectroscopy of nitrite complexes of methemoglobin.

The chemical interplay of nitrogen oxides (NO's) with hemoglobin (Hb) has attracted considerable recent attention because of its potential significance in the mechanism of NO-related vasoactivity regulated by Hb. An important theme of this interplay-redox coupling in adducts of heme iron and NO's-has sparked renewed interest in fundamental studies of FeNO(x) coordination complexes. In this Article, we report combined UV-vis and comprehensive electron paramagnetic resonance (EPR) spectroscopic studies that address intriguing questions raised in recent studies of the structure and affinity of the nitrite ligand in complexes with Fe(III) in methemoglobin (metHb). EPR spectra of metHb/NO(2)(-) are found to exhibit a characteristic doubling in their sharper spectral features. Comparative EPR measurements at X- and S-band frequencies, and in D(2)O versus H(2)O, argue against the assignment of this splitting as hyperfine structure. Correlated changes in the EPR spectra with pH enable complete assignment of the spectrum as deriving from the overlap of two low-spin species with g values of 3.018, 2.122, 1.45 and 2.870, 2.304, 1.45 (values for samples at 20 K and pH 7.4 in phosphate-buffered saline). These g values are typical of g values found for other heme proteins with N-coordinated ligands in the binding pocket and are thus suggestive of N-nitro versus O-nitrito coordination. The positions and shapes of the spectral lines vary only slightly with temperature until motional averaging ensues at approximately 150 K. The pattern of motional averaging in the variable-temperature EPR spectra and EPR studies of Fe(III)NO(2)(-)/Fe(II)NO hybrids suggest that one of two species is present in both of the alpha and beta subunits, while the other is exclusive to the beta subunit. Our results also reconfirm that the affinity of nitrite for metHb is of millimolar magnitude, thereby making a direct role for nitrite in physiological hypoxic vasodilation difficult to justify.

Moduli Space of (0,2) Conformal Field Theories

In this thesis we study aspects of (0,2) superconformal field theories (SCFTs), which are suitable for compactification of the heterotic string. In the first part, we study a class of (2,2) SCFTs obtained by fibering a Landau-Ginzburg (LG) orbifold CFT over a compact K\"ahler base manifold. While such models are naturally obtained as phases in a gauged linear sigma model (GLSM), our construction is independent of such an embedding. We discuss the general properties of such theories and present a technique to study the massless spectrum of the associated heterotic compactification. We test the validity of our method by applying it to hybrid phases of GLSMs and comparing spectra among the phases. In the second part, we turn to the study of the role of accidental symmetries in two-dimensional (0,2) SCFTs obtained by RG flow from (0,2) LG theories. These accidental symmetries are ubiquitous, and, unlike in the case of (2,2) theories, their identification is key to correctly identifying the IR fixed point and its properties. We develop a number of tools that help to identify such accidental symmetries in the context of (0,2) LG models and provide a conjecture for a toric structure of the SCFT moduli space in a large class of models. In the final part, we study the stability of heterotic compactifications described by (0,2) GLSMs with respect to worldsheet instanton corrections to the space-time superpotential following the work of Beasley and Witten. We show that generic models elude the vanishing theorem proved there, and may not determine supersymmetric heterotic vacua. We then construct a subclass of GLSMs for which a vanishing theorem holds.