Additional file 1: of Role of miR-146a in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders

Table S1. Detailed information of all patients and controls whose brain samples were used in this study. Table S2. Possibly deleterious variants in known ASD and ID genes. Table S3. DEGs identified in undifferentiated cells. Table S4. DEGs identified in differentiated cells. Table S5. Validation of RNA-Seq using RT-qPCR on Fluidigm array. Table S6. Top 20 cannonical pathways deregulated in undifferentiated cells. Table S7. Top 4 nodes enriched for protein-protein interaction as calculated by ClusterOne Plugin. Table S8. Top 20 cannonical pathways deregulated in the cell cycle modules of differentiated cells. Table S9. Top 20 cannonical pathways deregulated in the cell neuronal modules of differentiated cells. Table S10. Cell type enrichment analysis of DEGs from the Cell Cycle and Neuronal Modules. (XLSX 888 kb

Model results for Mekong River Delta, Wave 1 (December ‘03 –February ‘04).

<p>* Transform of the type log₁₀(1+x) was used</p><p>s.e. = standard error, Rank = rank of relative influence excluding the rank of the autoregressive term, AUC-ROC = Area Under the Curve of the Receiver Operating Characteristic, Trg = Training, Eval = Evaluation</p><p>Model results for Mekong River Delta, Wave 1 (December ‘03 –February ‘04).</p

Model results for Mekong River Delta, Wave 2 (December ‘04 –April ‘05).

<p>* Transform of the type log₁₀(1+x) was used</p><p>s.e. = standard error, Rank = rank of relative influence excluding the rank of the autoregressive term, AUC-ROC = Area Under the Curve of the Receiver Operating Characteristic, Trg = Training, Eval = Evaluation</p><p>Model results for Mekong River Delta, Wave 2 (December ‘04 –April ‘05).</p

Variations in variables across urbanicity classes for all of Vietnam.

<p>a: Variation of chicken density across urbanicity. b: Variation of fraction of land under rice across urbanicity. c: Variation of fraction of land under aquaculture across urbanicity. d: Variation of duck and geese flock size diversity across urbanicity. e: Variation of CTI across urbanicity. f: Variation of land-use diversity across urbanicity.</p

Model results for Red River Delta, Wave 1 (December ‘03 –February ‘04).

<p>* Transform of the type log₁₀(1+x) was used</p><p>s.e. = standard error, Rank = rank of relative influence excluding the rank of the autoregressive term, AUC-ROC = Area Under the Curve of the Receiver Operating Characteristic, Trg = Training, Eval = Evaluation</p><p>Model results for Red River Delta, Wave 1 (December ‘03 –February ‘04).</p

Additional file 1: of Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology

Profiling olfactory stem cells from living patients identifies miRNAs relevant for Autism pathophysiology. Figure S1. Relative expression of miRNAs in OMSC in validation round. Figure S2. Expression of reference miRNAs in fibroblasts. Figure S3. Expression of miRNA signature in PBMC. Figure S4. Long term potentiation pathway is predicted to be specifically targeted by miR-146a and miR-221. Table S1. Clinical descriptions of ASD patients whose OMSCs were used for miRNA screening. Table S2. Variants identified by whole exome analysis. Table S3. Genetic etiology of patients included in this analysis. Table S4. Primers used in this study. Table S5. Brief clinical descriptions of ASD patients whose primary skin fibroblasts and/or PBMC were used in follow up study. Table S6. Brief clinical descriptions of patients with ID whose primary skin fibroblasts were used in follow up study. Table S7. Selected enriched pathways predicted to be targeted by miR-146a and miR-221. (DOCX 1821 kb

Unadjusted coefficients (β) for the final set of predictors based on autologistic regression.

<p>^† Reference level,</p><p>* Transform of the type log₁₀(1+x) was used,</p><p>^#p values</p><p>Unadjusted coefficients (β) for the final set of predictors based on autologistic regression.</p

Model results for Viet Nam, Wave 2 (December ‘04 –April ‘05).

<p>* Transform of the type log₁₀(1+x) was used</p><p>s.e. = standard error, Rank = rank of relative influence excluding the rank of the autoregressive term, AUC-ROC = Area Under the Curve of the Receiver Operating Characteristic, Trg = Training, Eval = Evaluation</p><p>Model results for Viet Nam, Wave 2 (December ‘04 –April ‘05).</p

Additional file 2: of Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology

Raw expression value. (XLSX 115 kb

Discovery of a Novel Series of Potent and Orally Bioavailable Phosphoinositide 3-Kinase γ Inhibitors

The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3Kγ to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies. The in vitro activity of the first HTS hit, designated as the sulfonylpiperazine scaffold, was optimized utilizing structure-based design. However, nonoptimal pharmacokinetic properties precluded this series from further studies. An overlay of the X-ray structures of the sulfonylpiperazine scaffold and the second HTS hit within their complexes with PI3Kγ revealed a high degree of overlap. This feature was utilized to design a series of hybrid analogues including advanced leads such as <b>31</b> with desirable potency, selectivity, and oral bioavailability