Growth of a cohort of 100 <i>Celtis zenkeri</i> trees with a uniform initial diameter distribution.

<p>Projection time is yr. The time step of the matrix model is yr and the class width is column-wise (A) cm, (B) 0.9994 cm, and (C) 2.4985 cm. The top panel shows images of the transitions matrices between the initial and final times (i.e. the annual transition matrices raised to the power of ), where the starting class is column-wise, the ending class is row-wise, and the transition rates between classes are shown using heat colors (from white = zero to red = the highest values). The bottom panel shows the predicted dbh distributions: dotted line = initial dbh distribution (uniform across 10–14.997 cm); solid line = final dbh distribution according to the McKendrick continuous model; shaded bins = final dbh distribution according to the Usher matrix model.</p

Variance of the dbh growth rate versus one-year dbh increment for 53 tree species.

<p>Notice that axes are in logarithmic scale. The line is the regression line on log-transformed data.</p

Distribution across 53 species of the amplitude of variations of the population growth rate .

<p>Left boxplot: variations of when the class width varies from 1 to 10 cm, where . Right boxplot: amplitude of the 95% confidence interval of the estimate of for cm.</p

Additional file 1: Table S1. of Common variants in glucuronidation enzymes and membrane transporters as potential risk factors for colorectal cancer: a case control study

SNPs studied and their frequencies in our population. This table contains the description and frequencies of the SNP investigated in the study for ABCB1, UGT, MRP2, SLCO1B1 and SLCO1B2 genes. (DOCX 22 kb

Gross morphology of the cochlea isolated by microdissection.

<p><b>A–C</b>) Overview images of cochleae from a Tg(−);<i>Slc26a4</i>^Δ/Δ, Tg(+);<i>Slc26a4</i>^Δ/Δ and Tg(+);<i>Slc26a4</i>^Δ/+ mice. The width of the lower cochlear turn is marked with arrows and the round (RW) and oval window (OW) are labeled. A region with apparently thinner bone is marked (*). <b>D–F</b>) Enlarged view of the oval window. Normal otoconia in the saccule that reflect the light and appear bright white were seen in Tg(+);<i>Slc26a4</i>^Δ/Δ and Tg(+);<i>Slc26a4</i>^Δ/+ mice but not in Tg(−);<i>Slc26a4</i>^Δ/Δ (<i>arrow</i>). The number of mice represented by these images is 1 for <b>A</b> and <b>D</b>, and 3 pairs for images <b>B</b> & <b>C</b> and <b>E</b> & <b>F</b>.</p

Histology and pendrin expression in the cochlea.

<p>Staining in all images consisted of immunocytochemistry of pendrin (Pds #1 antibody; <i>red</i>), F-actin (<i>green</i>) and nucleic acids (<i>blue</i>). Images provide comparison of cryosections (<b>A–B</b>) and whole-mounted specimens (<b>C–E</b>) from Tg(+);<i>Slc26a4</i>^Δ/Δ mice to cryosections (<b>F–G</b>) and whole-mounted specimens (<b>H–J</b>) from Tg(−);<i>Slc26a4</i>^Δ/+ mice. Whole-mounted specimens in <b>C</b>, <b>E</b>, <b>H</b> and <b>J</b> were imaged by detecting fluorescence in 25 optical sections that were recorded in 1 µm intervals and projected into a single plane. Whole-mounted specimens in <b>D</b> and <b>I</b> were imaged by detecting fluorescence in 8 optical sections that were recorded in 1 µm intervals, projected into a single plane and overlaid onto a single brightfield image. The number of pairs of mice represented by these images are 2 for image <b>A</b> & <b>F</b>, 3 for <b>B</b> & <b>G</b>, and 1 for <b>C–E</b> & <b>H–J</b> with 3 sections being evaluated per animal. K, Kölliker's organ; OS, outer sulcus; Lim, spiral limbus; IS, inner sulcus; OC, organ of Corti; SP, spiral prominence; SV, stria vascularis; RM, Reissner's membrane. Additional images using an alternative anti-pendrin antibody (Pds #2) and alternative positive controls (Tg(+);<i>Slc26a4</i>^Δ/+ mice) are provided in the Supplement (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003641#pgen.1003641.s001" target="_blank">Fig. S1</a>).</p

Histology and pendrin expression in the vestibular labyrinth.

<p>Staining in all images consisted of immunocytochemistry of pendrin (Pds #1 antibody; <i>red</i>) and F-actin (<i>green</i>) and of nucleic acids (<i>blue</i>), the latter with the exception of images <b>B</b> and <b>F</b>. Images provide comparison of cryosections (<b>A, C–D</b>) and whole-mounted specimens (<b>B</b>) from Tg(+);<i>Slc26a4</i>^Δ/Δ to cryosections (<b>E, G–H</b>) and whole-mounted specimens (<b>F</b>) from Tg(−);<i>Slc26a4</i>^Δ/+ mice. Whole-mounted specimens were imaged by detecting fluorescence in 25 optical sections that were recorded in 1 µm intervals and projected into a single plane. The number of pairs of mice represented by these images are 2 for image <b>A</b> & <b>E</b>, 1 for <b>B</b> & <b>F</b>, 2 for <b>C</b> & <b>G</b>, and 2 for <b>D</b> & <b>H</b> with 3 sections being evaluated per animal. HC, vestibular hair cells; TC, transitional cells; M, melanocytes. Additional images using an alternative anti-pendrin antibody (Pds #2) and alternative positive controls (Tg(+);<i>Slc26a4</i>^Δ/+ mice) are provided in the Supplement (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003641#pgen.1003641.s002" target="_blank">Fig. S2</a>).</p

Pendrin expression evaluated by Western blotting.

<p>Proteins in crude membranes prepared from pooled inner ear tissues consisting of soft tissues from the cochlea and the vestibular labyrinth devoid of endolymphatic sac and crude membranes prepared from kidneys of Tg(−)<i>Slc26a4</i>^Δ/+, Tg(−)<i>Slc26a4</i>^Δ/Δ and Tg(+)<i>Slc26a4</i>^Δ/Δ mice were resolved by gel-electrophoresis and detected with an anti-pendrin antibody (Pds #1) and an anti-β-actin antibody. β-actin served as a loading control. <b>A</b>) Comparison of pendrin expression in membranes prepared from inner ears of Tg(−)<i>Slc26a4</i>^Δ/+, Tg(−)<i>Slc26a4</i>^Δ/Δ and Tg(+)<i>Slc26a4</i>^Δ/Δ mice to expression levels in descending amounts of membranes prepared from kidneys of Tg(−)<i>Slc26a4</i>^Δ/+ mice. <b>B</b>) Comparison of pendrin expression in membranes prepared from kidneys of Tg(−)<i>Slc26a4</i>^Δ/+, Tg(−)<i>Slc26a4</i>^Δ/Δ and Tg(+)<i>Slc26a4</i>^Δ/Δ mice. <b>C</b>) Expression levels of pendrin in descending amounts of membranes prepared from kidneys of Tg(+)<i>Slc26a4</i>^Δ/Δ mice. Data shown in <b>A</b>, <b>B</b> and <b>C</b> are each representative of 2 biological replicates.</p

Schematic diagram of the inner ear.

<p><b>A</b>) Diagram of the membranous labyrinth. The two continuous luminal fluid spaces of the mature inner ear are filled with endolymph (<i>pink</i> and <i>purple</i>). <b>B–E</b>) Diagrams of a cross section of one cochlear turn (<b>B</b>), of the utricle or saccule (<b>C</b>), of one ampulla (<b>D</b>) and the endolymphatic sac (<b>E</b>). Cells that express pendrin (<i>yellow cells</i> pointed to by <i>arrows</i>) are diagrammed in mature tissues.</p

<i>Atp1a1</i>, <i>Atp6v1b1</i>, <i>Slc26a4</i>, and <i>SLC26A4</i> mRNA levels in inner ear tissues.

<p>Expression was determined by quantitative RT-PCR performed on total RNA. Total RNA was isolated from microdissected tissues obtained from Tg(−);<i>Slc26a4</i>^Δ/+ (<b>A–D</b>) and Tg(+);<i>Slc26a4</i>^Δ/Δ mice (<b>E–H</b>). Endolymphatic sacs (ES) were isolated from mice at age E17.5. Cochleae were isolated at ages E17.5 (C1) and P2 (C2). Vestibular labyrinths (VL), consisted of saccule, utricle, ampullae and semicircular canals without endolymphatic sacs, were isolated at age P8. The expression of endogenous mouse <i>Atp1a1</i>, <i>Atp6v1b1</i>, and <i>Slc26a4</i>, and of transgenic human <i>SLC26A4</i> mRNA was normalized to the expression of 18S rRNA. Note that the expression pattern of human <i>SLC26A4</i> in Tg(+);<i>Slc26a4</i>^Δ/Δ mice resembles the pattern of mouse <i>Slc26a4</i> in Tg(−);<i>Slc26a4</i>^Δ/+ mice (both patterns <i>highlighted in red</i>). Numbers inside graphs represent the number of experiments.</p