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Mangelson, H.

Publications and source records attributed to Mangelson, H..

4 recordsLinked to original sources

Differential Expression of α,β, and γ Protocadherin Isoforms During Differentiation, Aging, and Cancer

The cadherin family of cell surface glycoproteins plays a fundamental role in cell-cell recognition, thereby participating in diverse biological process such as embryonic morphogenesis and oncogenic transformation. The subset of clustered protocadherin (PCDH) genes generated from the , {beta}, and {gamma} loci, have been widely studied for their potential role in neuronal cell-cell recognition and neurogenesis, however their broader role in normal embryonic development and cancer has not been examined in detail. We utilized human embryonic stem (hES) cells to model early human development in vitro, comparing PCDH isoform transcription in diverse types of embryonic progenitors with normal adult-derived and cancer counterparts. Embryonic progenitors express genes from the and {beta} cluster at levels comparable to that seen in the CNS, while fetal and adult-derived cells express primarily from the {gamma} cluster. Replicative senescence left fibroblasts with markedly lower expression of all isoforms. We observe that an embryonic pattern of clustered protocadherin gene expression and associated CpG island methylation is commonly associated with cancer cell lines from diverse tissue types. The differential regulation of the , {beta}, and {gamma} loci coincide with alternate regions of DNA accessibility at CTCF binding sites and lamina-associated domains and CPL expression correlated with the expression of LMNA and LMNB1. These observations support a potential role for the differential regulation of genes within the clustered protocadherin locus in selective cell-cell adhesion during embryogenesis, regeneration, cancer and aging.

developmental biology

Hi-C deconvolution of a textile-dye degrader microbiome reveals novel taxonomic landscapes and link phenotypic potential to individual genomes

Microbial biodiversity is represented by genomic landscapes populating dissimilar environments on earth. These genomic landscapes usually contain microbial functional signatures connected with the community phenotypes. Here we assess the genomic microbiodiversity landscape of a river associated microbiome enriched with 200 mg.mL-1 of anthraquinone Deep-Blue 35 (); we subjected to nutritional selection a composite sample from four different sites from a local river basin (Morelos, Mexico). This paper explores the resultant textile-dye microbiome, and infer links between predicted biodegradative functions and the individual genome fractions. By using a proximity-ligation deconvolution method, we deconvoluted 97 genome composites, with 80% of this been potentially novel species associated with the textile-dye environment. The main determinants of taxonomic composition were the genera Methanobacterium, Clostridium, and Cupriavidus constituting 50, 22, and 11 % of the total population profile respectively; also we observe an extended distribution of novel taxa without clear taxonomic standing. Removal of 50% chemical oxygen demand (COD) with 23% decolorization was observed after 30 days after dye enrichment. By metagenome wide analysis we postulate that sequence elements related to catalase-peroxidase, polyphenol oxidase, and laccase enzymes may be causally associated with the textile-dye degradation phenotype under our study conditions. This study prompts rapid genomic screening in order to select statistically represented functional features, reducing costs, and experimental efforts. As well as predicting phenotypes within complex communities under environmental pressures.

microbiology

Advancing pre-clinical species genetic utility through a high-quality assembly of the cynomolgus monkey (Macaca fascicularis) genome

The cynomolgus macaque is a non-human primate model, heavily used in biomedical research, but with outdated genomic resources. Here we have used the latest long-read sequencing technologies in order to assemble a fully phased, chromosome-level assembly for the cynomolgus macaque. We have built a hybrid assembly with PacBio, 10x Genomics, and HiC technologies, resulting in a diploid assembly that spans a length of 5.1 Gb with a total of 16,741 contigs (N50 of 0.86Mb) contained in 370 scaffolds (N50 of 138 Mb) positioned on 42 chromosomes (21 homologous pairs). This assembly is highly homologous to former assemblies and identifies novel inversions and provides higher confidence in the genetic architecture of the cynomolgus macaque genome. A demographic estimation is also able to capture the recent genetic bottleneck in the Mauritius population, from which the sequenced individual originates. We offer this resource as an enablement for genetic tools to be built around this important model for biomedical research.

genomics

The Genome of the Zebra Mussel, Dreissena polymorpha: A Resource for Invasive Species Research

The zebra mussel, Dreissena polymorpha, continues to spread from its native range in Eurasia to Europe and North America, causing billions of dollars in damage and dramatically altering invaded aquatic ecosystems. Despite these impacts, there are few genomic resources for Dreissena or related bivalves, with nearly 450 million years of divergence between zebra mussels and its closest sequenced relative. Although the D. polymorpha genome is highly repetitive, we have used a combination of long-read sequencing and Hi-C-based scaffolding to generate the highest quality molluscan assembly to date. Through comparative analysis and transcriptomics experiments we have gained insights into processes that likely control the invasive success of zebra mussels, including shell formation, synthesis of byssal threads, and thermal tolerance. We identified multiple intact Steamer-Like Elements, a retrotransposon that has been linked to transmissible cancer in marine clams. We also found that D. polymorpha have an unusual 67 kb mitochondrial genome containing numerous tandem repeats, making it the largest observed in Eumetazoa. Together these findings create a rich resource for invasive species research and control efforts.

genomics