Coefficient, Distortion and Growth Inequalities for Certain Close-to-Convex Functions

In the present investigation, certain subclasses of close-to-convex functions are investigated. In particular, we obtain an estimate for the Fekete-Szeg\"o functional for functions belonging to the class, distortion, growth estimates and covering theorems

Gene Function Classification Using Bayesian Models with Hierarchy-Based Priors

We investigate the application of hierarchical classification schemes to the annotation of gene function based on several characteristics of protein sequences including phylogenic descriptors, sequence based attributes, and predicted secondary structure. We discuss three Bayesian models and compare their performance in terms of predictive accuracy. These models are the ordinary multinomial logit (MNL) model, a hierarchical model based on a set of nested MNL models, and a MNL model with a prior that introduces correlations between the parameters for classes that are nearby in the hierarchy. We also provide a new scheme for combining different sources of information. We use these models to predict the functional class of Open Reading Frames (ORFs) from the E. coli genome. The results from all three models show substantial improvement over previous methods, which were based on the C5 algorithm. The MNL model using a prior based on the hierarchy outperforms both the non-hierarchical MNL model and the nested MNL model. In contrast to previous attempts at combining these sources of information, our approach results in a higher accuracy rate when compared to models that use each data source alone. Together, these results show that gene function can be predicted with higher accuracy than previously achieved, using Bayesian models that incorporate suitable prior information

Synpolydactyly and HOXD13 polyalanine repeat: addition of 2 alanine residues is without clinical consequences

<p>Abstract</p> <p>Background</p> <p>Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in <it>HOXD13</it>, resulting in an addition of ≥ 7 alanine residues to the polyalanine repeat. It has been suggested that expansions ≤ 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype.</p> <p>Methods</p> <p>We describe a large Pakistani and an Indian family with SPD. We perform detailed clinical and molecular analyses to identify the genetic basis of this malformation.</p> <p>Results</p> <p>We have identified four distinct clinical categories for the SPD1 phenotype observed in the affected subjects in both families. Next, we show that a milder foot phenotype, previously described as a separate entity, is in fact a part of the SPD1 phenotypic spectrum. Then, we demonstrate that the phenotype in both families segregates with an identical expansion mutation of 21 bp in <it>HOXD13</it>. Finally, we show that the HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine residues, evident in unaffected subjects of both families, is without clinical consequences.</p> <p>Conclusion</p> <p>It is the first molecular evidence supporting the hypothesis that expansion of ≤ 6 alanine residues in the HOXD13 polyalanine repeat is not associated with the SPD1 phenotype.</p

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

Early Lyme disease with spirochetemia - diagnosed by DNA sequencing

<p>Abstract</p> <p>Background</p> <p>A sensitive and analytically specific nucleic acid amplification test (NAAT) is valuable in confirming the diagnosis of early Lyme disease at the stage of spirochetemia.</p> <p>Findings</p> <p>Venous blood drawn from patients with clinical presentations of Lyme disease was tested for the standard 2-tier screen and Western Blot serology assay for Lyme disease, and also by a nested polymerase chain reaction (PCR) for <it>B. burgdorferi </it>sensu lato 16S ribosomal DNA. The PCR amplicon was sequenced for <it>B. burgdorferi </it>genomic DNA validation. A total of 130 patients visiting emergency room (ER) or Walk-in clinic (WALKIN), and 333 patients referred through the private physicians' offices were studied. While 5.4% of the ER/WALKIN patients showed DNA evidence of spirochetemia, none (0%) of the patients referred from private physicians' offices were DNA-positive. In contrast, while 8.4% of the patients referred from private physicians' offices were positive for the 2-tier Lyme serology assay, only 1.5% of the ER/WALKIN patients were positive for this antibody test. The 2-tier serology assay missed 85.7% of the cases of early Lyme disease with spirochetemia. The latter diagnosis was confirmed by DNA sequencing.</p> <p>Conclusion</p> <p>Nested PCR followed by automated DNA sequencing is a valuable supplement to the standard 2-tier antibody assay in the diagnosis of early Lyme disease with spirochetemia. The best time to test for Lyme spirochetemia is when the patients living in the Lyme disease endemic areas develop unexplained symptoms or clinical manifestations that are consistent with Lyme disease early in the course of their illness.</p

Implication of long-distance regulation of the HOXA cluster in a patient with postaxial polydactyly

Apparently balanced chromosomal inversions may lead to disruption of developmentally important genes at the breakpoints of the inversion, causing congenital malformations. Characterization of such inversions may therefore lead to new insights in human development. Here, we report on a de novo inversion of chromosome 7 (p15.2q36.3) in a patient with postaxial polysyndactyly. The breakpoints do not disrupt likely candidate genes for the limb phenotype observed in the patient. However, on the p-arm the breakpoint separates the HOXA cluster from a gene desert containing several conserved noncoding elements, suggesting that a disruption of a cis-regulatory circuit of the HOXA cluster could be the underlying cause of the phenotype in this patient

Alternative Splicing and Nonsense-Mediated RNA Decay Contribute to the Regulation of SHOX Expression

The human SHOX gene is composed of seven exons and encodes a paired-related homeodomain transcription factor. SHOX mutations or deletions have been associated with different short stature syndromes implying a role in growth and bone formation. During development, SHOX is expressed in a highly specific spatiotemporal expression pattern, the underlying regulatory mechanisms of which remain largely unknown. We have analysed SHOX expression in diverse embryonic, fetal and adult human tissues and detected expression in many tissues that were not known to express SHOX before, e.g. distinct brain regions. By using RT-PCR and comparing the results with RNA-Seq data, we have identified four novel exons (exon 2a, 7-1, 7-2 and 7-3) contributing to different SHOX isoforms, and also established an expression profile for the emerging new SHOX isoforms. Interestingly, we found the exon 7 variants to be exclusively expressed in fetal neural tissues, which could argue for a specific role of these variants during brain development. A bioinformatical analysis of the three novel 3′UTR exons yielded insights into the putative role of the different 3′UTRs as targets for miRNA binding. Functional analysis revealed that inclusion of exon 2a leads to nonsense-mediated RNA decay altering SHOX expression in a tissue and time specific manner. In conclusion, SHOX expression is regulated by different mechanisms and alternative splicing coupled with nonsense-mediated RNA decay constitutes a further component that can be used to fine tune the SHOX expression level