Clinical evaluation of nonsyndromic dental anomalies in Dravidian population: A cluster sample analysis.

AIM: To record the prevalence rate of dental anomalies in Dravidian population and analyze the percentage of individual anomalies in the population. METHODOLOGY: A cluster sample analysis was done, where 244 subjects studying in a dental institution were all included and analyzed for occurrence of dental anomalies by clinical examination, excluding third molars from analysis. RESULTS: 31.55% of the study subjects had dental anomalies and shape anomalies were more prevalent (22.1%), followed by size (8.6%), number (3.2%) and position anomalies (0.4%). Retained deciduous was seen in 1.63%. Among the individual anomalies, Talon's cusp (TC) was seen predominantly (14.34%), followed by microdontia (6.6%) and supernumerary cusps (5.73%). CONCLUSION: Prevalence rate of dental anomalies in the Dravidian population is 31.55% in the present study, exclusive of third molars. Shape anomalies are more common, and TC is the most commonly noted anomaly. Varying prevalence rate is reported in different geographical regions of the world.

D-AKAP2:PKA RII:PDZK1 ternary complex structure: insights from the nucleation of a polyvalent scaffold.

A-kinase anchoring proteins (AKAPs) regulate cAMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP2 (D-AKAP2/AKAP10) binds with high affinity to both RI and RII regulatory subunits of PKA and is anchored to transporters through PDZ domain proteins. Here, we describe a structure of D-AKAP2 in complex with two interacting partners and the exact mechanism by which a segment that on its own is disordered presents an α-helix to PKA and a ß-strand to PDZK1. These two motifs nucleate a polyvalent scaffold and show how PKA signaling is linked to the regulation of transporters. Formation of the D-AKAP2: PKA binary complex is an important first step for high affinity interaction with PDZK1, and the structure reveals important clues toward understanding this phenomenon. In contrast to many other AKAPs, D-AKAP2 does not interact directly with the membrane protein. Instead, the interaction is facilitated by the C-terminus of D-AKAP2, which contains two binding motifs-the D-AKAP2AKB and the PDZ motif-that are joined by a short linker and only become ordered upon binding to their respective partner signaling proteins. The D-AKAP2AKB binds to the D/D domain of the R-subunit and the C-terminal PDZ motif binds to a PDZ domain (from PDZK1) that serves as a bridging protein to the transporter. This structure also provides insights into the fundamental question of why D-AKAP2 would exhibit a differential mode of binding to the two PKA isoforms.

Granularity in granular cell ameloblastoma.

Granular cell ameloblastoma (GCA) is one of the rare histological variants of ameloblastoma (1.5-3.5%), identified by Krompechner in 1918 and is diagnosed by the characteristic presence of granular cells. These granular cells are seen in several physiological and pathological conditions and the granularity in GCA is due to lysosomal aggregates. This review is about the clinical features, histopathological features and differential diagnosis of GCA and also adds the theories for occurrence of granularity, electron microscopic findings, cell signaling pathways and immunohistochemistry findings related to these granular cells in GCA.

Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity.

A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RIalpha D/D domain alone and in complex with D-AKAP2. The D/D domain presents an extensive surface for binding through a well-formed N-terminal helix, and this surface restricts the diversity of AKAPs that can interact. The structures also underscore the importance of a redox-sensitive disulfide in affecting AKAP binding. An unexpected shift in the helical register of D-AKAP2 compared to the RIIalpha:D-AKAP2 complex structure makes the mode of binding to RIalpha novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.

In-house sulfur SAD phasing: a case study of the effects of data quality and resolution cutoffs.

Single-wavelength anomalous diffraction (SAD) utilizing the weak signal of inherently present S atoms can be successfully used to solve macromolecular structures, although this is mostly performed with data from a synchrotron rather than a laboratory source. Using high redundancy, sufficiently accurate anomalous data may now often be collected in the laboratory using Cu Kalpha X-ray radiation. Systematic analyses of a laboratory-derived data set illuminate the effects of data quality, redundancy and resolution cutoffs on the ability to locate the S atoms and phase the structure of Ptr ToxA, a 13.2 kDa toxin secreted by the fungus Pyrenophora tritici-repentis. Three sulfurs contributed to the successful phasing of the structure and were located using the program SHELXD. It is observed that data quality improves with increasing redundancy, but after a certain point becomes worse owing to crystal decay, so that there is an optimal amount of data to include for the sulfur substructure solution. Further, the success rate in locating S atoms is dramatically improved at lower resolutions and in a manner similar to data quality, there exists an optimal resolution at which the likelihood of solving the substructure is maximized. Based on these observations, a strategy for SAD data collection and substructure solution is suggested.

Structure of Ptr ToxA: an RGD-containing host-selective toxin from Pyrenophora tritici-repentis.

Tan spot of wheat (Triticum aestivum), caused by the fungus Pyrenophora tritici-repentis, has significant agricultural and economic impact. Ptr ToxA (ToxA), the first discovered proteinaceous host-selective toxin, is produced by certain P. tritici-repentis races and is necessary and sufficient to cause cell death in sensitive wheat cultivars. We present here the high-resolution crystal structure of ToxA in two different crystal forms, providing four independent views of the protein. ToxA adopts a single-domain, beta-sandwich fold of novel topology. Mapping of the existing mutation data onto the structure supports the hypothesized importance of an Arg-Gly-Asp (RGD) and surrounding sequence. Its occurrence in a single, solvent-exposed loop in the protein suggests that it is directly involved in recognition events required for ToxA action. Furthermore, the ToxA structure reveals a surprising similarity with the classic mammalian RGD-containing domain, the fibronectin type III (FnIII) domain: the two topologies are related by circular permutation. The similar topologies and the positional conservation of the RGD-containing loop raises the possibility that ToxA is distantly related to mammalian FnIII proteins and that to gain entry it binds to an integrin-like receptor in the plant host.

Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin.

Peroxiredoxins (Prxs) make up a ubiquitous class (proposed EC 1.11.1.15) of cysteine-dependent peroxidases with roles in oxidant protection and signal transduction. An intriguing biophysical property of typical 2-Cys Prxs is the redox-dependent modulation of their oligomeric state between decamers and dimers at physiological concentrations. The functional consequences of this linkage are unknown, but on the basis of structural considerations, we hypothesized that decamer-building (dimer-dimer) interactions serve to stabilize a loop that forms the peroxidatic active site. Here, we address this important issue by studying mutations of Thr77 at the decamer-building interface of AhpC from Salmonella typhimurium. Ultracentrifugation studies revealed that two of the substitutions (T77I and T77D) successfully disrupted the decamer, while the third (T77V) actually enhanced decamer stability. Crystal structures of the decameric forms of all three mutant proteins provide a rationale for their properties. A new assay allowed the first ever measurement of the true k(cat) and K(m) values of wild-type AhpC with H(2)O(2), placing the catalytic efficiency at 4 x 10(7) M(-)(1) s(-)(1). T77V had slightly higher activity than wild-type enzyme, and both T77I and T77D exhibited ca. 100-fold lower catalytic efficiency, indicating that the decameric structure is quite important for, but not essential to, activity. The interplay between decamer formation and active site loop dynamics is emphasized by a decreased susceptibility of T77I and T77D to peroxide-mediated inactivation, and by an increase in the crystallographic B-factors in the active site loop, rather than at the site of the mutation, in the T77D variant.

Crystal structure of a novel Plasmodium falciparum 1-Cys peroxiredoxin.

Plasmodium falciparum, the causative agent of malaria, is sensitive to oxidative stress and therefore the family of antioxidant enzymes, peroxiredoxins (Prxs) represent a target for antimalarial drug design. We present here the 1.8 A resolution crystal structure of P.falciparum antioxidant protein, PfAOP, a Prx that in terms of sequence groups with mammalian PrxV. The structure is compared to all 11 known Prx structures to gain maximal insight into its properties. We describe the common Prx fold and show that the dimeric PfAOP can be mechanistically categorized as a 1-Cys Prx. In the active site the peroxidatic Cys is over-oxidized to cysteine sulfonic acid, making this the first Prx structure seen in that state. Now with structures of Prxs in Cys-sulfenic, -sulfinic and -sulfonic acid oxidation states known, the structural steps involved in peroxide binding and over-oxidation are suggested. We also describe that PfAOP has an alpha-aneurism (a one residue insertion), a feature that appears characteristic of the PrxV-like group. In terms of crystallographic methodology, we enhance the information content of the model by identifying bound water sites based on peak electron densities, and we use that information to infer that the oxidized active site has suboptimal interactions that may influence catalysis. The dimerization interface of PfAOP is representative of an interface that is widespread among Prxs, and has sequence-dependent variation in geometry. The interface differences and the structural features (like the alpha-aneurism) may be used as markers to better classify Prxs and study their evolution.

Extracellular currents and potentials of the active myelinated nerve fiber.

This paper is concerned with the accurate and rapid calculation of extracellular potentials and currents from an active myelinated nerve fiber in a volume conductor, under conditions of normal and abnormal conduction. The neuroelectric source for the problem is characterized mathematically by using a modified version of the distributed parameter model of L. Goldman and J. S. Albus (1968, Biophys. J., 8:596-607) for the myelinated nerve fiber. Solution of the partial differential equation associated with the model provides a waveform for the spatial distribution of the transmembrane potential V(z). This model-generated waveform is then used as input to a second model that is based on the principles of electromagnetic field theory, and allows one to calculate easily the spatial distribution for the potential everywhere in the surrounding volume conductor for the nerve fiber. In addition, the field theoretic model may be used to calculate the total longitudinal current in the extracellular medium (I0L(z)) and the transmembrane current per unit length (im(z)); both of these quantities are defined in connection with the well-known core conductor model and associated cable equations in electrophysiology. These potential and current quantities may also be calculated as functions of time and as such, are useful in interpreting measured I0L(t) and im(t) data waveforms. An analysis of the accuracy of conventionally used measurement techniques to determine I0L(t) and im(t) is performed, particularly with regard to the effect of electrode separation distance and size of the volume conductor on these measurements. Also, a simulation of paranodal demyelination at a single node of Ranvier is made and its effects on potential and current waveforms as well as on the conduction process are determined. In particular, our field theoretic model is used to predict the temporal waveshape of the field potentials from the active, non-uniformly conducting nerve fiber in a finite volume conductor.