Structural biology and phylogenetic estimation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62633/1/388527a0.pd

Estimating equations for biomarker based exposure estimation under non-steady-state conditions

Unrealistic steady-state assumptions are often used to estimate toxicant exposure rates from biomarkers. A biomarker may instead be modeled as a weighted sum of historical time-varying exposures. Estimating equations are derived for a zero-inflated gamma distribution for daily exposures with a known exposure frequency. Simulation studies suggest that the estimating equations can provide accurate estimates of exposure magnitude at any reasonable sample size, and reasonable estimates of the exposure variance at larger sample sizes

Dentin dysplasia type I: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Dentin dysplasia is a rare hereditary disturbance of dentin formation characterized by defective dentin development with clinically normal appearing crowns, severe hypermobility of teeth and spontaneous dental abscesses or cysts. Radiographic analysis shows obliteration of all pulp chambers, short, blunted and malformed or absent roots and peri-apical radiolucencies of non carious teeth.</p> <p>Case presentation</p> <p>We present a case of dentin dysplasia type I in a 12-year-old Iranian boy, and the clinical, radiographic and histopathologic findings of this condition and treatment are described.</p> <p>Conclusions</p> <p>There are still many inconclusive issues in the diagnosis and management of patients with dentin dysplasia. The diagnostic features of this rare disturbance will remain incompletely defined until additional cases have been described. Early diagnosis of the condition and initiation of effective regular dental treatments may help these patients to prevent or delay loss of dentition.</p

Automatic Identification of Defects on Eggshell Through a Multispectral Vision System

The objective of this research was to develop an off-line artificial vision system to automatically detect defective eggshells, i.e., dirty or cracked eggshells, by employing multispectral images with the final purpose to adapt the system to an on-line grading machine. In particular, this work was focused to study the feasibility of identifying organic stains on brown eggshells (dirty eggshell), caused by blood, feathers, feces, etc., from natural stains, caused by deposits of pigments on the outer layer of clean eggshells. During the analysis a total of 384 eggs were evaluated (clean: 148, dirty: 236). Dirty samples were evaluated visually in order to classify them according to the kind of defect (blood, feathers, and white, clear or dark feces), and clean eggshells were classified on the basis of the colour of the natural stains (clear or dark). For each sample digital images were acquired by employing a Charged Coupled Device (CCD) camera endowed with 15 monochromatic filters (440-940 nm). A Matlab® function was developed in order to automate the process and analyze images, with the aim to classify samples as clean or dirty. The program was constituted by three major steps: first, the research of an opportune combination of monochromatic images in order to isolate the eggshell from the background; second, the detection of the dirt stains; third, the classification of the images samples into the dirty or clean group on the basis of geometric characteristics of the stains (area in pixel). The proposed classification algorithm was able to correctly classify near 98% of the samples with a very low processing time (0.05s). The robustness of the proposed classification was observed applying an external validation to a second set of samples (n = 178), obtaining similar percentage of correctly classified samples (97%)

Ab-Externo AAV-Mediated Gene Delivery to the Suprachoroidal Space Using a 250 Micron Flexible Microcatheter

The current method of delivering gene replacement to the posterior segment of the eye involves a three-port pars plana vitrectomy followed by injection of the agent through a 37-gauge cannula, which is potentially wrought with retinal complications. In this paper we investigate the safety and efficacy of delivering adeno-associated viral (AAV) vector to the suprachoroidal space using an ab externo approach that utilizes an illuminated microcatheter.6 New Zealand White rabbits and 2 Dutch Belted rabbits were used to evaluate the ab externo delivery method. sc-AAV5-smCBA-hGFP vector was delivered into the suprachoroidal space using an illuminated iTrackTM 250A microcatheter. Six weeks after surgery, the rabbits were sacrificed and their eyes evaluated for AAV transfection using immunofluorescent antibody staining of GFP.Immunostaining of sectioned and whole-mounted eyes demonstrated robust transfection in all treated eyes, with no fluorescence in untreated control eyes. Transfection occurred diffusely and involved both the choroid and the retina. No apparent adverse effects caused by either the viral vector or the procedure itself could be seen either clinically or histologically.The ab externo method of delivery using a microcatheter was successful in safely and effectively delivering a gene therapy agent to the suprachoroidal space. This method presents a less invasive alternative to the current method of virally vectored gene delivery

Comparison of Anterior Segment Optical Tomography Parameters Measured Using a Semi-Automatic Software to Standard Clinical Instruments

10.1371/journal.pone.0065559PLoS ONE86

Alteration of the bZIP60/IRE1 Pathway Affects Plant Response to ER Stress in Arabidopsis thaliana

The Unfolded Protein Response (UPR) is elicited under cellular and environmental stress conditions that disrupt protein folding in the endoplasmic reticulum (ER). Through the transcriptional induction of genes encoding ER resident chaperones and proteins involved in folding, the pathway contributes to alleviating ER stress by increasing the folding capacity in the ER. Similarly to other eukaryotic systems, one arm of the UPR in Arabidopsis is set off by a non-conventional splicing event mediated by ribonuclease kinase IRE1b. The enzyme specifically targets mature bZIP60 RNA for cleavage, which results in a novel splice variant encoding a nuclear localized transcription factor. Although it is clear that this molecular switch widely affects the transcriptome, its exact role in overall plant response to stress has not been established and mutant approaches have not provided much insight. In this study, we took a transgenic approach to manipulate the pathway in positive and negative fashions. Our data show that the ER-resident chaperone BiP accumulates differentially depending on the level of activation of the pathway. In addition, phenotypes of the transgenic lines suggest that BiP accumulation is positively correlated with plant tolerance to chronic ER stress

Mercury dynamics in a San Francisco estuary tidal wetland : assessing dynamics using in situ measurements

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Estuaries and Coasts 35 (2012): 1036-1048, doi:10.1007/s12237-012-9501-3.We used high-resolution in situ measurements of turbidity and fluorescent dissolved organic matter (FDOM) to quantitatively estimate the tidally driven exchange of mercury (Hg) between the waters of the San Francisco estuary and Browns Island, a tidal wetland. Turbidity and FDOM—representative of particle-associated and filter-passing Hg, respectively—together predicted 94 % of the observed variability in measured total mercury concentration in unfiltered water samples (UTHg) collected during a single tidal cycle in spring, fall, and winter, 2005–2006. Continuous in situ turbidity and FDOM data spanning at least a full spring-neap period were used to generate UTHg concentration time series using this relationship, and then combined with water discharge measurements to calculate Hg fluxes in each season. Wetlands are generally considered to be sinks for sediment and associated mercury. However, during the three periods of monitoring, Browns Island wetland did not appreciably accumulate Hg. Instead, gradual tidally driven export of UTHg from the wetland offset the large episodic on-island fluxes associated with high wind events. Exports were highest during large spring tides, when ebbing waters relatively enriched in FDOM, dissolved organic carbon (DOC), and filter-passing mercury drained from the marsh into the open waters of the estuary. On-island flux of UTHg, which was largely particle-associated, was highest during strong winds coincident with flood tides. Our results demonstrate that processes driving UTHg fluxes in tidal wetlands encompass both the dissolved and particulate phases and multiple timescales, necessitating longer term monitoring to adequately quantify fluxes.This work was supported by funding from the California Bay Delta Authority Ecosystem Restoration and Drinking Water Programs (grant ERP-00- G01) and matching funds from the United States Geological Survey Cooperative Research Program

Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition

In birds, as in mammals, one pair of chromosomes differs between the sexes. In birds, males are ZZ and females ZW. In mammals, males are XY and females XX. Like the mammalian XY pair, the avian ZW pair is believed to have evolved from autosomes, with most change occurring in the chromosomes found in only one sex—the W and Y chromosomes1, 2, 3, 4, 5. By contrast, the sex chromosomes found in both sexes—the Z and X chromosomes—are assumed to have diverged little from their autosomal progenitors2. Here we report findings that challenge this assumption for both the chicken Z chromosome and the human X chromosome. The chicken Z chromosome, which we sequenced essentially to completion, is less gene-dense than chicken autosomes but contains a massive tandem array containing hundreds of duplicated genes expressed in testes. A comprehensive comparison of the chicken Z chromosome with the finished sequence of the human X chromosome demonstrates that each evolved independently from different portions of the ancestral genome. Despite this independence, the chicken Z and human X chromosomes share features that distinguish them from autosomes: the acquisition and amplification of testis-expressed genes, and a low gene density resulting from an expansion of intergenic regions. These features were not present on the autosomes from which the Z and X chromosomes originated but were instead acquired during the evolution of Z and X as sex chromosomes. We conclude that the avian Z and mammalian X chromosomes followed convergent evolutionary trajectories, despite their evolving with opposite (female versus male) systems of heterogamety. More broadly, in birds and mammals, sex chromosome evolution involved not only gene loss in sex-specific chromosomes, but also marked expansion and gene acquisition in sex chromosomes common to males and females.National Science Foundation (U.S.)Howard Hughes Medical Institut

Transcriptome Analysis of Female and Male Xiphophorus maculatus Jp 163 A

Background: Xiphophorus models are important for melanoma, sex determination and differentiation, ovoviviparity and evolution. To gain a global view of the molecular mechanism(s) whereby gene expression may influence sexual dimorphism in Xiphophorus and to develop a database for future studies, we performed a large-scale transcriptome study. Methodology/Principal Findings: The 454-FLX massively parallel DNA sequencing platform was employed to obtain 742,771 and 721,543 reads from 2 normalized cDNA libraries generated from whole adult female and male X. maculatus Jp 163 A, respectively. The reads assembled into 45,538 contigs (here, a "contig" is a set of contiguous sequences), of which, 11,918 shared homology to existing protein sequences. These numbers estimate that the contigs may cover 53% of the total number of Xiphophorus transcriptome. Putative translations were obtained for 11,918 cDNA contigs, of which, 3,049 amino acid sequences contain Pfam domains and 11,064 contigs encode secretory proteins. A total of 3,898 contigs were associated with 2,781 InterPro (IPR) entries and 5,411 contigs with 132 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. There were 10,446 contigs annotated with 69,778 gene ontology (GO) terms and the three corresponding organizing principles. Fifty-four potential sex differentially expressed genes have been identified from these contigs. Eight and nine of these contigs were confirmed by real-time PCR as female and male predominantly expressed genes respectively. Based on annotation results, 34 contigs were predicted to be differentially expressed in male and female and 17 of them were also confirmed by real-time PCR. Conclusions/Significance: This is the first report of an annotated overview of the transcriptome of X. maculatus and identification of sex differentially expressed genes. These data will be of interest to researchers using the Xiphophorus model. This work also provides an archive for future studies in molecular mechanisms of sexual dimorphism and evolution, and can be used in comparative studies of other fish