Alzheimer’s: Targeting ApoE gene may ‘stop the disease’

Alzheimer’s: Targeting ApoE gene may ‘stop the disease’

. A new study published in the journal Nature has uncovered a new role for a gene known to be key in the development of Alzheimer’s disease: ApoE.
The team – led by Dr. Holtzman – investigated the effect of the ApoE4 gene variant in the development of Alzheimer’s disease. Dr. David Holtzman
Their findings suggest that ApoE4 may “work” by exacerbating the damage done by a different protein associated with Alzheimer’s: tau.
In fact, mice that lacked ApoE altogether did not exhibit any brain damage.
The team also found that the immune cells in the brains of mice with ApoE4 were activated, suggesting a strong inflammatory response. “But all forms of ApoE – even ApoE2 – are harmful to some extent when tau is aggregating and accumulating.
Once tau accumulates, the brain degenerates […] What we found was that when ApoE is there, it amplifies the toxic function of tau, which means that if we can reduce ApoE levels, we may be able to stop the disease process.”

Gut bacterial communities of diarrheic patients with indications of Clostridioides difficile infection

Gut bacterial communities of diarrheic patients with indications of Clostridioides difficile infection

We present bacterial 16S rRNA gene datasets derived from stool samples of 44 patients with diarrhea indicative of a Clostridioides difficile infection.
After processing of paired-end sequencing data, reads were merged, quality-filtered, primer sequences removed, reads truncated to 400 bp and dereplicated.
The bacterial community profiles are based on operational taxonomic unit (OTU, defined at 97% genetic identity) frequency in stool samples of 44 patients with diarrhea indicative of C. difficile infection and 35 asymptomatic control individuals (n=79).
Occurrence of diarrhea in patents is indicated by plus (patient exhibited diarrhea) and minus (no diarrhea), results from microbiological diagnosis of C. difficile infection (C. d. m. t.) are shown below (plus, positively tested for C. difficile; minus, negatively tested for C. difficile).
Full size image Non-metric multidimensional scaling (NMDS) based on weighted Unifrac12 was used to display the bacterial community structure in 79 stool samples at same sequencing effort (10.000 reads per sample).
Full size image We present bacterial 16S rRNA gene datasets derived from stool samples of 44 patients with diarrhea indicative of a Clostridioides difficile infection.
After processing of paired-end sequencing data, reads were merged, quality-filtered, primer sequences removed, reads truncated to 400 bp and dereplicated.
The bacterial community profiles are based on operational taxonomic unit (OTU, defined at 97% genetic identity) frequency in stool samples of 44 patients with diarrhea indicative of C. difficile infection and 35 asymptomatic control individuals (n=79).
Occurrence of diarrhea in patents is indicated by plus (patient exhibited diarrhea) and minus (no diarrhea), results from microbiological diagnosis of C. difficile infection (C. d. m. t.) are shown below (plus, positively tested for C. difficile; minus, negatively tested for C. difficile).
Full size image Non-metric multidimensional scaling (NMDS) based on weighted Unifrac12 was used to display the bacterial community structure in 79 stool samples at same sequencing effort (10.000 reads per sample).

Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis

Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis

Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity.
e Representative images of SMAD1 expression (white; arrows identify expression in the sinusoidal endothelium), VWF (green), SMA (red) and DAPI (blue) in liver tissue from Erg fl/fl and Erg cEC-het mice (Scale bar 50 μm). g Representative image of TGFβ2 expression in HUVEC transfected with control or ERG siRNA by immunofluorescence; nuclei are identified by DRAQ V and cells are co-stained for ERG (green). h Representative images of TGFβ2 expression (white; arrows) in large vessel within the liver from Erg fl/fl and Erg cEC-het mice (Scale bar 50 μm).
f Protein−protein interactions between ERG, SMAD1, SMAD2 and SMAD3 were assessed by Co-IP assay in whole cell lysate from HUVEC.
ChIP-qPCR analysis of HUVEC was assessed following treatment with c and d TGFβ2 or PBS for 30 min, or e and f control or ERG siRNA.
j Quantification of SMAD2/3 target gene expression by qPCR in liver tissue of Erg fl/fl mice injected with etanercept and CCL4 compared to CCL4 alone (*) or Erg cEC-Het treated with etanercept and CCL4 compared to CCL4 alone (#).
Filled white arrows identify CD31+ERG+ EC whereas empty white arrows show CD31+ERG− EC (Scale bar 50 µm).

Quantifying the relative immune cell activation from whole tissue/organ-derived differentially expressed gene data

Quantifying the relative immune cell activation from whole tissue/organ-derived differentially expressed gene data

S14b–d and Supplementary Fig. S14b–d and Supplementary Fig.
2b) but not in bCD.IP (Fig. 2b) but not in bCD.IP (Fig.
For the GSE7768 contamination analysis, we plotted the gene expression data (x-axis) together with our reference CV values (y-axis) for all nine samples (Supplementary Fig. For the GSE7768 contamination analysis, we plotted the gene expression data (x-axis) together with our reference CV values (y-axis) for all nine samples (Supplementary Fig.
S7 and Supplementary Fig.
The resultant ICEPOP score for each cell type, SR, and CRT for mouse (Supplementary Fig. The resultant ICEPOP score for each cell type, SR, and CRT for mouse (Supplementary Fig.
In the LPS analysis (Supplementary Fig.

A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease

A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease

All four Traj18-partial deletion mouse lines harbored similar Traj gene segments as WT B6 mice, except for Traj18 (Fig.
(a) TCRα repertoire diversity analyzed by next generation sequencing.
Frequencies of iNKT cells in the spleen and liver from WT B6 and Traj18−/− (1-1 L) mice were analyzed by flow cytometry, which revealed iNKT cell-deficiency in Traj18−/− (1-1 L) mice (Fig. Analysis of developmental stages of thymocytes revealed no difference between Traj18−/− (1-1 L) and WT B6 mice (Supplemental Fig. We also analyzed the frequencies of T cells with specific functions such as type 2 NKT cells, regulatory T cells (Treg) and mucosal-associated invariant T (MAIT) cells in the thymus, resulting in no differences between Traj18−/− (1-1 L) and WT B6 mice (Supplemental Fig.
Because some functional studies on iNKT cells require animals on a genetic background distinct from the B6 strain, we also generated a Traj18−/− (1-1 L) BALB/c mouse line by backcrossing, and confirmed the absence of iNKT cells and cytokine production in response to α-GalCer stimulation (Supplemental Fig.
However, divergent findings for the metabolic role of iNKT cells have been reported in studies using the previously generated Traj18−/− mouse strain.
Among the experimental groups on HFD, both Traj18−/− (1-1 L) and Cd1d−/− mice gained less weight than WT B6 mice, whereas there was no significant difference in the weight gain between Traj18−/− (1-1 L) and Cd1d−/− mice (Fig.
Another new Traj18−/− mouse line generated by Dashtsoodol et al. also contained similar Trav1-Traj33 expression levels as WT B6 mice13, indicating normal MAIT cell development and cell number.