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1.
Figure 7

Figure 7. From: Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.

The interplay of cell types and pathways in SALS pathology. Combining pathways and candidate genes differentially expressed in the motor cortex of SALS patients reveals a complex interplay of cellular processes and cell types. Candidate genes corresponding to major pathways discussed in the main text are color-coded, placed in the cell type(s) where they most likely exert their influence, and their individual up- () or down-regulation () is indicated. Genes EIF4A2, GNAS, and NAP1L5 are left out for clarity.

Carsten W Lederer, et al. BMC Genomics. 2007;8:26-26.
2.
Figure 1

Figure 1. From: Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.

Architecture of the motor cortex in SALS and control samples. Nissl staining of representative SALS samples (D2, D4, D5) and controls (H1, H3, H4) shows the intact architecture of the motor cortex in samples chosen for expression analysis. All samples are shown at identical magnification. Cell layers are color-coded as indicated for sample D2. ML – molecular layer; EGL – external granular layer; EPL – external pyramidal layer; IGL – internal granular layer; IPL – internal pyramidal layer; MFL – multiform layer; WM – white matter. The scale bar indicates 500 μm.

Carsten W Lederer, et al. BMC Genomics. 2007;8:26-26.
3.
Figure 4

Figure 4. From: Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.

Comparison of microarray and qRT-PCR results for selected candidate genes. The bar graph shows mean results of expression levels in SALS vs. control subject. Fold-changes are shown diseased vs. control, and differed by less than 1.2-fold between qRT-PCR and microarray, except for MT1E and MT2A. Error bars for qRT-PCR data indicate the range for duplicate experiments. The P values for qRT-PCR and microarray (most significant probe) data were 0.342 and 0.020 (MT1E), 0.063 and 0.023 (MT1G), 0.037 and 0.025 (MT1L), 0.119 and 0.026 (MT1M), 0.074 and 0.031 (MT1X), 0.063 and 0.011 (MT2A), and 0.037 and 0.011 (PVALB).

Carsten W Lederer, et al. BMC Genomics. 2007;8:26-26.
4.
Figure 5

Figure 5. From: Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.

Changes of ANXA2, ATP1A3, NRGN, and PVALB mRNAs in motor cortex of SALS subjects. In-situ hybridization analysis of ANXA2, ATP1A3, NRGN, and PVALB mRNAs was performed in duplicate tissue sections of motor cortex from five control and five SALS subjects. Optical density values were normalized against those obtained in control subjects and subjected to two-tailed Student's t-test (with the P values 3.44e-6 (ANXA2), 7.91e-3 (ATP1A3), 2.29e-5 (NRGN) and 2.88e-6 (PVALB), respectively, diseased vs. control). The bar graph shows mean results and the standard deviation of the mean of labeling in control and SALS subjects.

Carsten W Lederer, et al. BMC Genomics. 2007;8:26-26.
5.
Figure 3

Figure 3. From: Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.

Genes differentially expressed in motor cortex of SALS subjects. 57 of 19,431 quality-filtered genes (0.3%), represented by 61 probes, are differentially expressed (corrected P < 0.05), with each row in the matrix representing a single probe and each column a subject. Normalized expression levels are represented by the color of the corresponding cell, relative to the median abundance of each gene for each subject (see scale). Genes are named using their UniGene symbol and arranged in a hierarchical cluster (standard correlation) based on their expression patterns, combined with a dendrogram whose branch lengths reflect the relatedness of expression patterns. For each gene the fold-change (diseased vs. control) and corrected P value are given.

Carsten W Lederer, et al. BMC Genomics. 2007;8:26-26.
6.
Figure 2

Figure 2. From: Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.

Gene Ontology nodes differentially expressed in motor cortex of SALS subjects. Significant Gene Ontology (GO) nodes were combined to groups likely representing major processes in the context of ALS pathology, specifically energy metabolism, ion homeostasis and solute transport, defense signaling, protein modification and turnover, cytoskeleton, and glycolysis, and are arranged indicating the predominant intracellular localization of the gene products they comprise. The basic categories Biological Process, Cellular Component, and Molecular Function are color-coded. Connecting arrows indicate the order of nodes in the GO hierarchy. For each major process only the highest node(s) of significance (◇) and the most significant node (!) are shown per basic category. Up- () and down-regulation (), the absolute number and percentage of genes meeting the criterion, z score, and corrected P value are indicated for each node. Redundant nodes are left out within the same category, or combined if in different categories.

Carsten W Lederer, et al. BMC Genomics. 2007;8:26-26.
7.
Figure 6

Figure 6. From: Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.

Immunodetection of selected candidate genes. (A) Immunoblots for ANXA2, AQP1, NRGN, and CANX was performed for three control and six diseased subjects. The size of quantified bands is indicated in kDa. The glycosylated form of AQP1 (*), undetectable in the healthy samples analyzed, was not included in the analysis. CANX served as a reference gene for sample normalization. (B) Bar graph comparing fold-changes of mean expression levels diseased vs. control as detected by immunoblot and microarray. Normalized intensity values are shown diseased vs. control and were analyzed by a two-tailed Student's t-test. P values for immunoblot and microarray (most significant probe) data were 0.025 and 0.011 (ANXA2), 0.055 and 0.036 (AQP1), and 0.047 and 0.023 (NRGN), respectively). (C) Immunofluorescence detection of AQP1 expression in non-neuronal cells in the diseased (D) and the healthy (H) motor cortex. NF – neurofilaments (red); AQP1 – aquaporin 1 (green); DNA – Hoechst33342 counterstain (blue). The scale bar indicates 100 μm.

Carsten W Lederer, et al. BMC Genomics. 2007;8:26-26.

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