Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene

Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n = 22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n = 13), benign neurofibromas (NF) (n = 26) and MPNST (n = 6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 – strongly expressed in NF1-related tumours – caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1

Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as A biomarker and survival gene

Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n - 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n = 22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n = 13), benign neurofibromas (NF) (n = 26) and MPNST (n = 6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumours - caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1

Baltimore Urban Gardening

The student film “Baltimore Urban Gardening” highlights the benefits of creating spaces for and using locally grown produce

Exploring the internal exposome of seminal plasma with semen quality and live birth: A Pilot Study

Infertility is clinically defined as the inability to achieve pregnancy within 12 months of regular unprotected sexual intercourse and affects 15% of couples worldwide. Therefore, the identification of novel biomarkers that can accurately predict male reproductive health and couples’ reproductive success is of major public health significance. The objective of this pilot study is to test whether untargeted metabolomics is capable of discriminating reproductive outcomes and understand associations between the internal exposome of seminal plasma and the reproductive outcomes of semen quality and live birth among ten participants undergoing assisted reproductive technology (ART) in Springfield, MA. We hypothesize that seminal plasma offers a novel biological matrix by which untargeted metabolomics is able to discern male reproductive status and predict reproductive success. The internal exposome data was acquired using UHPLC-HR-MS on randomized seminal plasma samples at UNC at Chapel Hill. Unsupervised and supervised multivariate analyses were used to visualize the differentiation of phenotypic groups classified by men with normal or low semen quality based on World Health Organization guidelines as well as by successful ART: live birth or no live birth. Over 100 exogenous metabolites, including environmentally relevant metabolites, ingested food components, drugs and medications, and metabolites relevant to microbiome-xenobiotic interaction, were identified and annotated from the seminal plasma samples, through matching against the NC HHEAR hub in-house experimental standard library. Pathway enrichment analysis indicated that fatty acid biosynthesis and metabolism, vitamin A metabolism, and histidine metabolism were associated sperm quality; while pathways involving vitamin A metabolism, C21-steroid hormone biosynthesis and metabolism, arachidonic acid metabolism, and Omega-3 fatty acid metabolism distinguished live birth groups. Taken together, these pilot results suggest that seminal plasma is a novel matrix to study the influence of the internal exposome on reproductive health outcomes. Future research aims to increase the sample size to validate these findings.</p

Data from: Methodological congruence in phylogenomic analyses with morphological support for teiid lizards (Sauria: Teiidae)

A well-known issue in phylogenetics is discordance among gene trees, species trees, morphology, and other data types. Gene-tree discordance is often caused by incomplete lineage sorting, lateral gene transfer, and gene duplication. Multispecies-coalescent methods can account for incomplete lineage sorting and are believed by many to be more accurate than concatenation. However, simulation studies and empirical data have demonstrated that concatenation and species tree methods often recover similar topologies. We use three popular methods of phylogenetic reconstruction (one concatenation, two species tree) to evaluate relationships within Teiidae. These lizards are distributed across the United States to Argentina and the West Indies, and their classification has been controversial due to incomplete sampling and the discordance among various character types (chromosomes, DNA, musculature, osteology, etc.) used to reconstruct phylogenetic relationships. Recent morphological and molecular analyses of the group resurrected three genera and created five new genera to resolve non-monophyly in three historically ill-defined genera: Ameiva, Cnemidophorus, and Tupinambis. Here, we assess the phylogenetic relationships of the Teiidae using “next-generation” anchored-phylogenomics sequencing. Our final alignment includes 316 loci (488,656 bp DNA) for 244 individuals (56 species of teiids, representing all currently recognized genera) and all three methods (ExaML, MP-EST, and ASTRAL-II) recovered essentially identical topologies. Our results are basically in agreement with recent results from morphology and smaller molecular datasets, showing support for monophyly of the eight new genera. Interestingly, even with hundreds of loci, the relationships among some genera in Tupinambinae remain ambiguous (i.e. low nodal support for the position of Salvator and Dracaena)

Locus partitions for Teiidae multiple sequence alignment

Locus partitions for Teiidae multiple sequence alignmen

Teiidae Concatenated Sequence Alignment

Teiidae Concatenated Sequence Alignmen

Pairwise Alignments for Probe Design

Pairwise Alignments for Probe Desig

Teiidae Probe Sequences

Teiidae Probe Sequence