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

Additional file 3: of Neuronal sphingosine kinase 2 subcellular localization is altered in Alzheimer’s disease brain

Percentage of amyloid area according to fields. This percentage was calculated on the whole population of 25 cases. Field 1 corresponded to the cortex immediately under the pial surface and field 10 reached the white matter. Due to the poor representativeness of fields 1 (non tissular zone and pial surface) and 10 (proximal white matter), they were not included in statistical analysis for the cortical areas. The distribution of cortical layers was consistent with previously reported morphological studies ([18]; [17]). For instance, in frontal and entorhinal cortices, the cortical layer I was principally found in fields 1 and 2, cortical layers II and III were mostly represented in fields 2 to 6, layer IV was confined in fields 6 to 8, and layers V and VI were found in fields 7 to 10. Moreover, the Aβ deposits were more frequent in cortical layers II and III. As the fields were examined at a magnification of × 400, each field was 300 μM × 150 μM in size. (TIFF 35 kb

Additional file 2: of Neuronal sphingosine kinase 2 subcellular localization is altered in Alzheimer’s disease brain

Visualization of amyloid deposits was carried out using a DAPI staining. Our preliminary studies showed that DAPI stains the nuclei as well as plaques in gray matter. In order to validate that DAPI stained extracellular deposits are amyloid deposits, an immunofluorescent staining of Aβ peptide was realized with a mouse primary antibody (Dako, mouse clone 6 F/3D, Ref. M0872, 1:100). Immunofluorescence study was performed on paraffin-embedded, formalin-fixed human brain sections. Secondary antibody of goat anti-mouse IgG (Life technologies, Alexa Fluor® 488, Ref. A-11001, 1:1000) was used for visualization. DAPI was used as a nuclear counterstain (final concentration of 1 μg/mL). The merge confocal composite image was analyzed with ImageJ 1.51o software and was confirmed the colocalization. (TIFF 284 kb

Additional file 3: Figure S3. of Reduced Tau protein expression is associated with frontotemporal degeneration with progranulin mutation

Reduction of Tau protein expression does not result from greater post-mortem delay, aberrant RIN or cortical atrophy in FTLD-TDP-GRNlτ brains. (a) Fixed hemibrain weight, (b) post-mortem delay and (c) RIN (RNA Integrity Number) of FTLD-TDP-GRNlτ, FTLD-TDP-C9ORF72, sporadic FTLD-TDP, sporadic FTLD-FUS and control brains. Results are expressed as means ± SEM. For statistical analysis the Kruskal-Wallis test was used (*p < 0.05; ns non significant). a.u arbitrary unit, SEM: standard error of the mean. (TIF 164 kb

Additional file 2: Figure S2. of Reduced Tau protein expression is associated with frontotemporal degeneration with progranulin mutation

Conservation of several proteins among the different FTLD subclasses. (a) Western blot analysis of NSE (Neuron Specific Enolase), Aconitase, Histone H3 and Heavy (NF-H) Neurofilaments protein level in control and FTLD-U brain samples. Are shown representative data from FTLD-TDP-GRNlτ (n = 8), FTLD-TDP-C9ORF72 (n = 10), sporadic FTLD-TDP (n = 8), sporadic FTLD-FUS (n = 5) and control brains (n = 8). (b) Protein levels were quantified and normalized to a pool containing same protein amount of each control used in this study. Actin was used as loading control. Results are expressed as means ± SEM. For statistical analysis the Kruskal-Wallis test was used (ns non significant). SEM: standard error of the mean. (TIF 223 kb

Additional file 1: Figure S1. of Reduced Tau protein expression is associated with frontotemporal degeneration with progranulin mutation

Preservation of Tau mRNA in FTLD-TDP-GRNlτ group. qPCR analysis was done on total Tau mRNA in control and FTLD brain samples. Both 5’UTR (Untranslated Region) and E11-12 (Exons 11–12) primers target regions present in all Tau transcripts. Data were normalized to the mean value of control cases with Large Ribosomal Protein P0 (RPLP0) used as reference gene. Results are expressed as means ± SEM. For statistical analysis the Mann–Whitney test was used (ns non significant), n = 5–10/group. SEM: standard error of the mean. (TIF 176 kb