Plum pudding random medium model of biological tissue toward remote microscopy from spectroscopic light scattering

Biological tissue has a complex structure and exhibits rich spectroscopic behavior. There is \emph{no} tissue model up to now able to account for the observed spectroscopy of tissue light scattering and its anisotropy. Here we present, \emph{for the first time}, a plum pudding random medium (PPRM) model for biological tissue which succinctly describes tissue as a superposition of distinctive scattering structures (plum) embedded inside a fractal continuous medium of background refractive index fluctuation (pudding). PPRM faithfully reproduces the wavelength dependence of tissue light scattering and attributes the "anomalous" trend in the anisotropy to the plum and the powerlaw dependence of the reduced scattering coefficient to the fractal scattering pudding. Most importantly, PPRM opens up a novel venue of quantifying the tissue architecture and microscopic structures on average from macroscopic probing of the bulk with scattered light alone without tissue excision. We demonstrate this potential by visualizing the fine microscopic structural alterations in breast tissue (adipose, glandular, fibrocystic, fibroadenoma, and ductal carcinoma) deduced from noncontact spectroscopic measurement

Frequencies of specific re-arrangements in putamen mtDNA.

<p>(A) Frequency of the common deletion per mtDNA (mtDNA⁻¹), (B) Major-arc deletions, (C) CRMs, (D) CRDs. Bars indicate cohort medians. (E) Frequency of the common deletion (Common) versus major arc deletions excluding the common deletion (Major arc), linear regression shown with R². (F) Changes in the levels of the common deletion as a proportion of cumulative major arc deletions excluding the common deletion (CD/MA) relative to age.</p

Characteristic landscape of mtDNA rearrangements in putamen.

<p>(A–C) 5′ and 3′ breakpoint position frequencies from representative young (A) and aged (B) specimens, and (C) detail of control region from (B). mtDNA map below (A) and (B) depicts rRNA genes (blue), tRNA genes (black bars), protein coding genes (white) and the control region (red). Map uses alternate numbering with a contiguous control region and m.1 as the 5′ base of <i>MT-TF</i>. In the map below (C), the top bar depicts the control region (light shading) with features indicated left to right (dark shading): termination associated sequence; conserved sequence boxes I, II (CSBII (red)), and III; light-strand promoter and heavy strand promoter-1. Middle bar shows the 7S DNA with an arrow at the 3′ end and lower bar marks heavy strand origin of replication (OH). The first base of conventional numbering is indicated (m.1). Where present (A–C), i = common deletion, ii = 3′ clustered breakpoints, iii = CRMs, iv = CRDs. (D) Dot-plot of mtDNA breakpoint distribution from (A) and (E) breakpoint distribution from (B) with axes colored accordingly and data normalized for coverage. Equivalent data to that in panels A–E for all samples is presented in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003990#pgen.1003990.s001" target="_blank">Figs. S1</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003990#pgen.1003990.s003" target="_blank">S3</a> & <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003990#pgen.1003990.s004" target="_blank">S4</a>. (F) Upper panel, resolution of large amplicons from PCR of CRMs using inverted primers; Lower panel, PCR of CRDs using a breakpoint-specific primer. Sample order for both panels as in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003990#pgen.1003990.s010" target="_blank">Table S1</a>. Molecular weight markers indicated (Kb).</p

Strand bias for transitions.

<p>(A) Average frequencies for each base change in the coding region and (B) the control region of the young and aged cohorts, (± SD). (C) Magnitude of [G>A]-[C>T] bias (ΔSNV bp⁻¹, the difference between G>A and C>T frequencies) and (D) [T>C]-[A>G] bias in the coding region. (E) Magnitude of [G>A]-[C>T] bias and (F) [T>C]-[A>G] bias in the control region. (G) Frequency of m.64C>T and m.16148C>T. Bars indicate cohort medians.</p

Additional file 2: of STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations

Western blots of CHIP in mutation carriers. (DOCX 241 kb

Updated pedigree of the Parry family.

<p>Individuals included in this study are indicated with star symbols on top of individual's number. The proband is marked with an arrow. One of the individuals in generation V was marked V-1A in order to match the individual numbers with the ones in the initially published Parry pedigree, reference 5.</p

Haplotype reconstruction with genetic markers in <i>DNAJC5</i>.

<p>Two informative homozygous discordant genotypes close to the Leu116del change indicate that the Parry family does not share a haplotype with either of the two families reported in Noskova et al supporting a mutational hotspot rather than a founder effect. Grey: Noskova et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029729#pone.0029729-Noskova1" target="_blank">[4]</a> haplotypes; Red: Discordant homozygous genotypes; all markers appear in their genomic order from centromere to telomere.</p

Clinical manifestations in probands from the families or sporadic affected individuals included in the study.

<p>Clinical manifestations in probands from the families or sporadic affected individuals included in the study.</p

Pedigree diagrams of families with <i>SLITRK1</i> variants.

<p>Pedigrees for individuals in whom <i>SLITRK1</i> variants were identified. Each obsessive-compulsive (OC) spectrum proband is labeled with his/her identifier and is designated by a black arrowhead. Individuals affected with an OC spectrum disorder are represented by shaded symbols, with red shading indicating obsessive-compulsive disorder (OCD) and blue shading indicating Tourette syndrome (TS). Psychiatric conditions outside of the OC spectrum are represented by a magenta circle in the center of the symbol. Male family members are represented with squares, females with circles, persons with unspecified gender are diamonds with the number of individuals indicated directly below. All psychiatric pathology is listed under each affected individual. OCD – Obsessive-Compulsive Disorder, TS – Tourette syndrome, BDD – Body Dysmorphic Disorder, GAD – Generalized Anxiety Disorder, MDD – Major Depressive Disorder, N.O.S. – not otherwise specified, PD – Panic Disorder, PTSD – Post-Traumatic Stress Disorder, w/ - with, y/o – years old, ? – psychiatric history is unavailable for the individual.</p

Identification of DNA variants in <i>DNAJC5</i> and <i>PRPF6</i>.

<p>a) Schematic of the region on chromosome 20 containing <i>DNAJC5</i> and <i>PRPF6</i> in close proximity. b) Sanger sequence traces of the identified segregating variants in <i>DNAJC5</i> and <i>PRPF6</i>. c) The two very rare changes identified in the Parry family Leu116del (in <i>DNAJC5</i>) and N477S (in <i>PRPF6</i>) were highly conserved in different species. A second change in <i>DNAJC5</i>, Leu115Arg, was also highly conserved.</p